FitSugar

What Causes Hiccups?

FitSugar — Fri, 27 Jul 2007 03:30:00 -0700

Everyone and their mother seems to have a unique cure for a bad case of the hiccups, but what I want to know is, what causes them in the first place?

A hiccup is an unintentional contraction of your diaphragm, the muscle that separates your chest from your abdomen. It plays an important role in breathing, and when it contracts, it makes your vocal cords close briefly and that's what causes the sound of a hiccup.

Hiccups are actually triggered by many things:

Eating spicy foods - It can cause irritation to the nerves that control normal contractions of your diaphragm.
Eating a large meal, eating too fast (swallowing air), or drinking carbonated beverages - These can cause your stomach to expand, which pushes up your diaphragm, making hiccups more likely.
Drinking alcohol - Alcohol can relax your diaphragm and vocal cords, making it easier for other factors to trigger hiccups.
Tobacco use - Tobacco use may irritate the nerves that control the diaphragm.

Want to know what else can cause hiccups? Then read more

Sudden temperature changes - Whether the change occurs inside your body (like drinking hot tea), or outside your body (when you go outside in the snow), it can cause hiccups.
Excitement or emotional stress - It's not clear why this can cause hiccups, but it may have to do with one of the nerves involved in the hiccup reflex being startled.

As annoying as hiccups can be, even if you don't sip water through a straw while pinching your nose, or hold your breath while saying the word "hippopotamus" in your head 5 times, hiccups will eventually go away on their own. Very rarely do hiccups last for more than 20-30 minutes. If they do, like this poor girl who had them for 3 weeks straight, there could be an underlying medical problem such as nerve damage. If this is the case, someone should definitely seek medical attention pronto.

Source

Carpal tunnel syndrome

FitSugar — Wed, 08 Oct 2008 17:34:56 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Overview

Several medical conditions can increase the risk for, or even cause, carpal tunnel syndrome (CTS). Diabetes, hypothyroidism, rheumatoid arthritis, osteoarthritis, obesity, and pregnancy are the main conditions associated with CTS. Many of the underlying diseases that contribute to the development of CTS are also associated with more severe forms of CTS.

Most workers who use their hands and wrists repetitively are at risk for CTS. This is especially true if they work in cold temperatures and have medical conditions that make them susceptible to CTS.

Being overweight consistently turns up as a risk factor for CTS and may play a direct causal role in CTS.

Treatment News:

Several physical therapy techniques have been shown to improve hand strength and function in patients with mild-to-moderate CTS.
Short periods of traction have also been successful in producing long-term relief in patients who have failed other conventional treatments.
Injections of botulinum toxin (Botox) show promise in treating carpal tunnel syndrome.

Risk Factors:

A Swedish study of neurological diseases found CTS to be the second most commonly occurring nerve, nerve root, and nerve plexus disorder among siblings hospitalized with the same condition. Although the study could not distinguish between genetic and environmental causes, clusters of CTS in families may suggest an inherited predisposition.

Introduction

Carpal tunnel syndrome (CTS) is a disorder marked by weakness and pain in the hand and wrist. CTS occurs in the nerves of the hands -- not the muscles, as some people believe. The symptoms of CTS can be incapacitating.

To understand how carpal tunnel syndrome arises, it is important to know the parts of the hand and wrist that are involved.

The Carpal Tunnel. The carpal tunnel is a passageway that forms beneath the strong, broad transverse ligament. This ligament is a bridge that extends across the lower palm and connects the bones of the wrist (carpals), which form an arch below the tunnel.

The Median Nerve and Flexor Tendons. The median nerve and nine flexor tendons pass under the ligament bridge and through the carpal tunnel (similar to a river). They extend from the forearm and up into the hand:

The flexor tendons are fibrous cords that connect to muscles of the fingers (two to each finger) and one to the thumb. They allow flexing of the fingers and clenching of the fist.
The median nerve plays two important roles. It supplies sensation to the thumb, index, middle, and ring fingers, and to the flexor tendons. It provides function for the muscles at the base of the thumb (the thenar muscle).

The median nerve travels through a compartment in the wrist called the carpal tunnel. The ligaments that transverse the nerve are not very flexible. Any swelling within the wrist compartment can put excessive pressure on structures such as the blood vessels and the median nerve. Excessive pressure can constrict blood flow and cause nerve damage. The symptoms from the compression cause pain, loss of sensation, and decreased function in the hand.

It is not completely known how the process leading to carpal tunnel syndrome actually evolves, and how nerve conduction (the passing of the nerve signal) through the wrist becomes changed. In general, carpal tunnel syndrome develops when the tissues around the median nerve swell and press on the nerve. Early in the disorder, the process is reversible. Over time, however, the insulation on the nerves may wear away, and permanent nerve damage may develop.

The following events have been observed in the hands of people with carpal tunnel syndrome:

The protective lining of tendons (called the tenosynovium) swells within the carpal tunnel. Some research suggests that this swelling is caused by build-up of fluid (called synovial fluid) under the lining. Synovial fluid lubricates and protects the tendons.
The transverse ligament, the band of fibrous tissue that forms the roof over the median nerve, becomes thicker and broader.
The swollen tendons and thickened ligament compress the median nerve fibers, just as stepping on a hose slows the flow of water through it. The effect is to reduce blood flow and oxygen supply to the nerve, slowing the transmission of nerve signals through the carpal tunnel. Some cases of carpal tunnel syndrome may be due to enlargement of the median nerve rather than compression by surrounding tissues.

The result is pain, numbness, and tingling in the wrist, hand, and fingers. Only the little finger is unaffected by the median nerve.

Click the icon to see a depiction of carpal tunnel syndrome.

Symptoms

Symptoms of carpal tunnel syndrome usually progress gradually over weeks and months and sometimes years. Anyone with recurrent or persistent pain, numbness and tingling, or weakness of the hand should consult a doctor for a diagnosis. Symptoms often develop as follows:

Initial symptoms include pain in the wrist and hand. Symptoms commonly occur in both hands. (Even when only one hand is painful, the other hand often shows signs of nerve conduction abnormalities on testing.)
Early on, the patient also usually reports numbness, tingling, burning, or some combination on the palm side of the index, middle, and ring fingers. (Typically the fifth finger has no symptoms.) Such sensations may radiate to the forearm or shoulder.
Over time, the hand may become numb, and patients may lose the ability to feel heat and cold. Patients may experience a sense of weakness and a tendency to drop things.
Patients may feel that their hands are swollen even though there is no visible swelling. This symptom may actually prove to be an important indicator of greater severity.

Symptoms may occur not only when the hand is being used but also at night when the patient is at rest. Even in cases where work is suspected as the cause, symptoms typically first occur outside of work. In fact, the disorder may be distinguished from similar conditions by pain occurring at night after going to bed.

Causes

Biologic Causes. Carpal tunnel syndrome (CTS) is considered an inflammatory disorder caused by repetitive stress, physical injury, or medical conditions. It is often very difficult, however, to determine the precise cause of carpal tunnel syndrome. No tests are available to identify a specific cause. Except in patients with certain underlying diseases, the biologic mechanisms leading to carpal tunnel syndrome are unknown. Although an overactive immune response that causes inflammation and damage in the joints or muscles is responsible for a number of arthritic conditions, similar problems are not likely to play an important role in CTS. More likely, reduced blood flow and lack of oxygen are important in the process leading to progressive swelling and scarring.

Working Conditions versus Medical Problems. Although some studies suggest that more than half of CTS cases are associated with workplace factors, there is no strong evidence of a cause and effect relationship. In fact, most studies now strongly suggest that carpal tunnel syndrome is primarily associated with medical or physical conditions such as diabetes, osteoarthritis, hypothyroidism, and rheumatoid arthritis. CTS also tends to occur in people with certain genetic or environmental risk factors such as obesity, smoking, alcohol abuse, or significant mental stress. Of all nerve, nerve root, and nerve plexus disorders, CTS has one of the highest familial risks, implying some type of genetic origin. When such susceptible people are subjected to repetitive hand or wrist work, the risk for CTS can become significant. CTS, then, is very likely to be due to convergences of factors that lead to nerve damage in the hand.

Worker's Compensation and CTS. The issues surrounding workers' compensation are particularly troubling in determining accurately whether labor conditions cause carpal tunnel pain. CTS is a major contributor to workers' compensation cases.

High Force and Vibration. Even though medical and physical conditions may be the initial culprits leading to CTS, certain working conditions are especially related to nerve damage -- if not to pure cases of CTS. Work that involves high force or vibration is particularly hazardous, as is repetitive hand and wrist work in cold temperatures.

In addition to CTS, other disorders of hand and wrist result from these work-related movements. They include the following:

Hand-arm vibration syndrome -- tingling and numbing that persist even after the vibration stops
Cumulative trauma (repetitive stress) disorder
Overuse syndromes
Chronic upper limb pain syndrome

All of these problems are generally associated with repetitive and forceful use of the hands, resulting in damaged muscles and bones of the upper arms.

Psychosocial Factors in the Workplace. Studies indicate that psychosocial factors in the workplace, such as intense deadlines, a poor social work environment, and low levels of job satisfaction, are major contributors to carpal tunnel pain. Such psychosocial conditions are more likely to be important factors in contributing to CTS in office workers, although they also complicate the condition in workers whose work is primarily physical.

A number of medical conditions increase the risk for or even cause CTS. The main conditions associated with CTS are diabetes, hypothyroidism, rheumatoid arthritis, osteoarthritis, obesity, and pregnancy. Many of the underlying diseases that contribute to the development of CTS are also associated with more severe forms of CTS.

Diabetes. CTS is a very common feature of diabetic neuropathy, one of the major complications of diabetes. Neuropathy is decreased or distorted nerve function; it particularly affects sensation. Symptoms include numbness, tingling, weakness, and burning sensations, usually starting in the fingers and toes and moving up to the arms and legs. About 6% of patients with CTS have diabetes. A 2005 study reported that an estimated 85% of patients with type 1 diabetes develop CTS. Development of CTS was related to the patient's age and the length of time they had diabetes. The development of diabetes-related complications, such as kidney disease, is not related to the development of CTS in people with diabetes.

Autoimmune Diseases. In autoimmune diseases, the body's immune system abnormally attacks its own tissue, causing widespread inflammation, which, in many cases, affects the carpal tunnel of the hand. Such autoimmune diseases include rheumatoid arthritis, systemic lupus erythematosus, and hypothyroidism. Some experts believe that CTS may actually be one of the first symptoms in a number of these diseases. Studies also suggest that CTS patients with these disorders are more likely to have severe CTS that requires surgery.

Diseases that Affect Muscle and Bones. Arthritis, gout, and other medical conditions that damage the muscles, joints, or bones in the hand may cause changes that lead to CTS. In fact, in one 2000 study, susceptibility to muscle and bone diseases was the major risk factor for CTS in British women. Osteoporosis (loss of bone density), although not a direct cause of CTS, increases the risk for wrist fractures that can lead to CTS.

Injuries and Previous Surgeries. Injuries, fractures, and operations that affect the forearm, wrist, or hand may lead to CTS, sometimes many years after the event.

Structural Abnormalities. Inborn abnormalities in the bones of the hand, wrist, or forearm may contribute to CTS.

Chronic Kidney Insufficiency. People who undergo hemodialysis for chronic kidney damage often experience a build-up in the hand of a certain type of protein called beta 2-microglobulin. This build-up can result in CTS. The longer the person has been receiving hemodialysis, the greater the risk of CTS. Certain drugs and procedures (particularly one procedure called hemodiafiltration) are being investigated as having the potential to reduce microglobulin build-up. It is hoped such new methods will delay the need for carpal tunnel surgery in patients undergoing long-term hemodialysis.

Other Diseases. A number of other medical conditions may cause or increase susceptibility to CTS:

Down syndrome
Amyloidosis (a progressive disorder of the connective tissues)
Acromegaly (a disease that leads to abnormally large hands and feet due to excessive growth hormone)
Tumor on the median nerve (removal of the tumor often resolves the CTS in such cases)

Medications. According to case reports, a number of medications may increase the risk for temporary CTS. They include certain medications that affect the immune system (such as interleukin-2), and anticlotting drugs (such as warfarin). There has been conflicting evidence as to whether corticosteroids and hormone replacement therapy may increase risk. More research is warranted before a causal association can be established.

Bone dislocations and fractures can narrow the carpal tunnel, thereby exerting pressure on the median nerve.

Being overweight consistently turns up as a risk factor for CTS and may play a direct causal role on CTS. Greater body mass appears to reduce nerve flow speed into the hand. Obesity is also related to poor physical fitness, which may also increase risk. A 2005 analysis indicated that weight is strongly linked to the onset of CTS in patients under the age of 63 years, but may be a less important factor as they get older.

Hormonal fluctuations in women play a role in CTS. Such fluctuations may cause fluid retention and other changes in the body that cause swelling. Fluid retention is one reason that CTS may develop during pregnancy.

CTS is strongly associated with a family history of the disorder. Many of these cases can be attributed to physical characteristics or medical conditions associated with CTS, which also run in families. However, in one study, 17% of family clusters of CTS were not associated with any such medical conditions, suggesting the genetic factors may be important in some people. Carpal tunnel syndrome that develops in young people is most likely to have a genetic component.

A 2000 study suggested that some patients with CTS may have a genetic defect that produces higher levels of a certain collagen subtype. Collagen is the protein used to build all connective tissue, muscle, bones, and ligament. The collagen found in CTS patients tends to produce stiffness.

Other genetic factors that may contribute to this disorder include abnormalities in certain genes that regulate myelin, a fatty substance that serves as insulation for nerve fibers.

Risk Factors

Evidence suggests that about 3% of women and 2% of men will be diagnosed with carpal tunnel syndrome during their lifetimes, with peak prevalence in women older than 55. Still, determining how many people actually have CTS is very difficult. Many people report CTS symptoms and have normal test results. Other people have no symptoms and abnormal results. Furthermore, some evidence suggests that, after an apparent a decline in cases, the prevalence of CTS is rising.

A large 2005 study of more than 1,000 patients found that the severity of CTS was mild in 42% of patients, moderate in 18%, and severe in 40%. Patients were an average of about 48 years old. More than five times as many women then men participated in the study.

Older people are at higher risk than younger adults. It is very rare in children.

Many studies indicate that women have a significantly higher risk for carpal tunnel syndrome than men do. According to the National Institutes of Health, women are three times more likely than men to experience carpal tunnel syndrome. The explanation for this greater risk is unknown but may be related to the smaller size of women's carpal tunnel.

Hormonal changes appear to play a major role in CTS.

A 2005 study reported that 17% of pregnant women had CTS. Nearly one-quarter of those had it in both wrists. Early studies have presented conflicting reports regarding when CTS is most likely to occur during pregnancy. One found that most cases occurred in the third trimester, and weight gain increased the risk. Another concluded that CTS developed at any point during the pregnancy. New-onset CTS during pregnancy that is severe and persistent enough to require treatment is uncommon. Most cases go away on their own after delivery. However, in one study, 11% of women reported CTS six months after delivery, and 4.3% of them still had the condition a year afterward.

Breastfeeding has also been linked to flare-ups of inflammatory disorders such as CTS. Breastfeeding temporarily lowers the level of natural steroid hormones.

CTS has also been shown to increase during:

The postpartum period
Menopause

Other conditions that are more specific to women than men may increase their risk for carpal tunnel syndrome:

The hand-intensive nature of housework and typing may contribute to a higher incidence of CTS in women.
Women are also at a much higher risk for autoimmune disorders than men are; such disorders are significantly linked to CTS.

People with close relatives who have carpal tunnel syndrome have a higher risk of developing CTS themselves. This risk may be due to family histories of medical conditions associated with CTS, obesity, or genetic factors.

A number of illnesses, skeletal abnormalities, and injuries can predispose individuals to carpal tunnel syndrome, including autoimmune diseases and arthritic conditions.

At high risk are those whose occupations combine force and repetition of the same motion in the fingers and hand for long periods.

Virtually all workers who use their hands and wrists repetitively are at risk for CTS, particularly if they work in cold temperatures and have factors or medical conditions that make them susceptible.

Computer Users and Typists. Repetitive typing and key entry is highly associated with missing work due to CTS. The risk for CTS in this group, however, is still much lower than with occupations involving heavy labor. Although more than 10% of the computer users complain of CTS symptoms, the evidence implicating computer use as a major cause of CTS is weak. One small 2001 study reported that nerve conduction tests on frequent computer users showed the same rate of CTS (3.5%) as in the general population.

A 2003 study found an association between mouse-use (not keyboard use) and CTS. Typing speed may affect risk in some cases, however. For example, the fingers of typists whose speed is 60 words per minute exert up to 25 tons of pressure each day. In one study, typists with CTS struck the keys with greater force than those without the disorder. A large Danish study showed no increased risk of CTS among people who use computers at work. Another study of workers who used computers heavily (up to 7 hours per day) found no increased risk of CTS among them.

Other Very High-Risk Workers. Workers in the meat and fish packing industries and those who assemble airplanes have the highest risk for CTS, according to one study. Meat packers complained of pain and loss of hand function as long ago as the 1860s. Even today, the incidence of carpal tunnel syndrome in the meat, poultry, and fish packing industries may be as high as 15%. A 2005 study of automobile assembly workers found that the estimated annual rate of CTS ranged from 1 - 10%.

Musicians. Musicians are at very high risk for CTS and other problems related to the muscles and nerves in the hands, upper trunk, and neck. In one study, 20% reported CTS or other nerve disorders in the hands and wrists.

Highest to Lowest Numbers of CTS Events by Job. The following is a list of occupations published by the Bureau of Labor Statistics in 2002 rating workers with highest to lowest total numbers of CTS-related events:

Assemblers
Cashiers
Secretaries
General office clerks
Laborers, non-construction
Bookkeepers, accounting, and auditing clerks
Welders and cutters
Data-entry employees
Textile sewing machine operators
Order clerks
Supervisors and proprietors, sales occupations
Machine operators (unspecified)
Truck drivers
Insurance adjusters, examiners, and investigators
Electrical and electronic equipment assemblers
Packaging and filling machine operators
Janitors and cleaners
Bank tellers
Production inspectors, checkers, and examiners

SOURCES: Bureau of Labor Statistics, U.S. Department of Labor, April 2002

At Home and At Play. People who intensively cook, knit, sew, do needlepoint, play computer games, do carpentry, or extensively use power tools are at increased risk for CTS. Long-distance cycling may make symptoms of carpal tunnel syndrome worse.

Square Wrists. Some (but not all) studies have reported a higher risk for CTS in people with square wrists (the thickness and width are about the same) than in those with the more common rectangular wrists.

Palm Shape. In one study, patients with palms that were both shorter and wider than average, and who also had shorter third fingers, were more likely to have CTS than those without these hand characteristics.

Poor Upper Back Strength. Some researchers claim that poor upper back strength makes people more susceptible to poor posture and injuries in the upper extremities, including carpal tunnel syndrome.

Cigarette smoking slows down blood flow, so that smokers have worse symptoms and slower recovery than nonsmokers do. Increased alcohol intake has been associated with CTS in people with other risk factors.

Poor nutrition, previous injuries, and stress can increase one's risk for carpal tunnel syndrome. In addition, high levels of so-called “bad” cholesterol (low-density lipoprotein, or LDL) have also been linked to an increased risk of CTS.

Prognosis

Carpal tunnel syndrome can range from a minor inconvenience to a disabling condition, depending on its cause and persistence and the individual characteristics of the patient. Many cases of CTS are mild, and when symptoms are of short duration, they often resolve (disappear) on their own. Once a woman with pregnancy-associated CTS gives birth, for instance, the swelling in her wrists and other symptoms almost always subside. Proper treatment of other medical conditions that cause CTS can often help reduce wrist swelling.

In severe untreated cases, however, the thenar muscles at the base of the thumb may whither, and loss of sensation may be permanent. CTS can become so crippling that people can no longer do their jobs or even perform simple tasks at home.

Carpal tunnel syndrome exacts a psychological toll. Anyone who cannot use his or her hands is likely to be depressed and suffer from low self-esteem. People may suffer from daily pain. In severe cases, they may be unable to perform ordinary tasks, such as driving a car or carrying groceries. And equally or even more distressing, they may have to give up enjoyable sports and hobbies.

According to a 2005 report from the Bureau of Labor Statistics, among the major disabling diseases and illnesses, carpal tunnel syndrome was associated with the longest average time away from work (28 days).

Employees with CTS who try to work through the disorder often put more stress on the wrists to compensate for the weakness and pain. The end result is to make the condition worse and impair work performance.

Eventually, the worker with CTS may be forced to give up his or her livelihood. In one study, nearly half of all patients with CTS changed jobs within 30 months of an initial diagnosis. And because of the controversy surrounding the issue of carpal tunnel syndrome and workers compensation, it is not always certain that the worker will receive compensation payments.

Prevention

Because multiple factors may cause carpal tunnel syndrome, there is no single mode of prevention. Treating any underlying medical condition is certainly important. Simple common sense may help minimize some risk factors predisposing a person to work-related CTS or other cumulative trauma disorders. A patient can learn how to adjust the work area, handle tools, or perform tasks in ways that put less stress on the hands and wrists. Proper posture and exercise programs to strengthen the fingers, hands, wrists, forearms, shoulders, and neck may help prevent CTS.

Many companies are now taking action to help prevent repetitive stress injuries. In a major survey, 84% reported that they were modifying equipment, tasks, and processes. Nearly 85% were analyzing their workstations and jobs, and 79% were buying new equipment. It should be stressed, however, that there has been no evidence that any of these methods can provide complete protection against CTS. The optimal corporate approach, if possible, is to reallocate workers suffering from repetitive stress injuries to other jobs.

Altering the way a person performs repetitive activities may help prevent inflammation in the hand and wrist from progressing into carpal tunnel syndrome. For example, replacing old tools with ergonomically designed new ones can be very helpful.

Rest Periods and Avoiding Repetition. Anyone who does repetitive tasks should begin with a short warm-up period, take frequent breaks, and avoid overexertion of the hand and finger muscles whenever possible. Employers should be urged to vary tasks and work content.

A 2001 study conducted by the National Institute for Occupational Safety and Health reported that even taking multiple "microbreaks" (about 3 minutes each) reduces strain and discomfort without decreasing productivity. Such breaks may include the following:

Shaking or stretching the limbs
Leaning back in the chair
Squeezing the shoulder blades together.
Taking deep breaths

Good Posture. Good posture is extremely important in preventing carpal tunnel syndrome, particularly for typists and computer users.

The worker should sit with the spine against the back of the chair with the shoulders relaxed.
The elbows should rest along the sides of the body, with wrists straight.
The feet should be firmly on the floor or on a footrest.
Typing materials should be at eye level so that the neck does not bend over the work.
Keeping the neck flexible and head upright maintains circulation and nerve function to the arms and hands. One method for finding the correct head position is the "pigeon" movement. Keeping the chin level, glide the head slowly and gently forward and backward in small movements, avoiding neck discomfort.

Good Office Furniture. Poorly designed office furniture is a major contributor to bad posture. Chairs should be adjustable for height, with a supportive backrest. Custom-designed chairs, made for people who do not fit in standard chairs, can be expensive. However, the costs are often offset by the savings in medical expenses that follow injuries related to bad posture.

Voice Recognition Software. For CTS patients who must use a computer frequently, a variety of voice recognition software packages (ViaVoice, Voice Xpress, Dragon NaturallySpeaking, IListen) are now available, enabling virtually hands-free computer use.

Keyboard and Mouse Tips. Anyone using a keyboard and mouse has some options that may help protect the hands.

The tension of the keys should be adjusted so they can be depressed without excessive force.
The hands and wrists should remain in a relaxed position to avoid excessive force on the keyboard.
A 2003 study suggested that mouse-use poses a higher risk than keyboard use. Replacing the mouse with a trackball device and the standard keyboard with a jointed-type keyboard are helpful substitutions.
Wrist rests, which fit under most keyboards, can help keep the wrists and fingers in a comfortable position.
Some people recommend keeping the computer mouse as close to the keyboard and the user's body as possible, to reduce shoulder muscle movement.
The mouse should be held lightly, with the wrist and forearm relaxed. New mouse supports (ErgoCat) are also available that relieve stress on the hand and support the wrist.
Some people cut their mouse pads in half to reduce movement.

Innovative keyboard designs may reduce hand stress:

Alternative geometry keyboards (Microsoft Natural Keyboard, Apple Adjustable Keyboard) allow the user to adjust and modify hand positions as well as adjust key tension. Most have a split or "slanted" keyboard that places the wrists at an angle. Studies suggest they are useful in promoting a neutral position for the wrist.
The continuous passive motion (CPM) keyboard lifts and declines gently and automatically every three minutes to break tension on the hands and wrist. A report of a clerical worker with CTS who used this device found an overall improvement of 10 words per minute in the typing tests, a decrease in disability score and symptom severity, and an improvement in function.
A keyless keyboard (orbiTouch) is an innovative device that uses two domes. The typist covers the domes with his or her hands and slides them into different positions that represent letters.

The force placed on the fingers, hands, and wrists by a repetitive task is an important contributor to CTS. To alleviate the effect of force on the wrist, tools and tasks should be designed so that the wrist position is the same as it would be if the arms dangled in a relaxed manner at the sides.

No task should require the wrist to deviate from side to side or to remain flexed or highly extended for long periods.
The handles of hand tools such as screwdrivers, scrapers, paint brushes, and buffers should be designed so that the force of the worker's grip is distributed across the muscle between the base of the thumb and the little finger, not just in the center of the palm.
People who need to hold any tools (including pencils and steering wheels) for long periods of time should grip them as loosely as possible.
In order to apply force appropriately, the ability to feel an object is extremely important. Tools with textured handles are helpful.
If possible, people should avoid working at low temperatures, which reduces sensation in hands and fingers.
Power tools and machines should be designed to minimize vibrations.
Wearing thick gloves, when possible, may lessen the shock transmitted to the hands and wrists. One 2001 study found, however, that wearing gel-padded gloves clearly increased comfort but did not actually protect against compression-induced CTS.

Hand and wrist exercises may help reduce the risk of developing carpal tunnel syndrome. Isometric and stretching exercises can strengthen the muscles in the wrists and hands, as well as the neck and shoulders, improving blood flow to these areas. Performing the simple exercises described below for 4 to 5 minutes every hour may be helpful.

Wrists

Exercise 1.

Make a loose right fist, palm up, and use the left hand to press gently down against the clenched hand.
Resist the force with the closed right hand for 5 seconds. Be sure to keep the wrist straight.
Turn the right fist palm down, and press the knuckles against the left open palm for 5 seconds.
Finally, turn the right palm so the thumb-side of the fist is up, and press down again for 5 seconds.
Repeat with the left hand.

Exercise 2.

Hold one hand straight up shoulder-high with fingers together and palm facing outward. (The position looks like a shoulder-high salute.)
With the other hand, bend the hand being exercised backward with the fingers still held together and hold for 5 seconds.
Spread the fingers and thumb open while the hand is still bent back and hold for 5 seconds.
Repeat five times for each hand.

Exercise 3. (Wrist Circle)

Hold the second and third fingers up, and close the others.
Draw five clockwise circles in the air with the two finger tips.
Draw five more counterclockwise circles.
Repeat with the other hand.

Fingers and Hand

Exercise 1.

Clench the fingers of one hand into a fist tightly.
Release, fanning out the fingers.
Do this five times. Repeat with the other hand.

Exercise 2.

To exercise the thumb, bend it against the palm beneath the little finger, and hold for 5 seconds.
Spread the fingers apart, palm up, and hold for 5 seconds.
Repeat five to 10 times with each hand.

Exercise 3.

Gently pull the thumb out and back and hold for 5 seconds.
Repeat five to 10 times with each hand.

Forearms (stretching these muscles will reduce tension in the wrist)

Place the hands together in front of the chest, fingers pointed upward in a prayer-like position.
Keeping the palms flat together, raise the elbows to stretch the forearm muscles.
Stretch for 10 seconds.
Gently shake the hands limp for a few seconds to loosen them.
Repeat frequently when the hands or arms tire from activity.

Neck and Shoulders

Exercise 1.

Sit upright and place the right hand on top of the left shoulder.
Hold that shoulder down, and slowly tip the head down toward the right.
Keep the face pointed forward, or even turned slightly toward the right.
Hold this stretch gently for 5 seconds.
Repeat on the other side.

Exercise 2.

Stand in a relaxed position with the arms at the side.
Shrug the shoulders up, then squeeze the shoulders back, then stretch the shoulders down, and then press them forward.
The entire exercise should take about 7 seconds.

Diagnosis

Carpal tunnel syndrome (CTS) is most accurately diagnosed using the patients' descriptions of symptoms, and electrodiagnostic tests that measure nerve conduction through the hand. If electrodiagnostic testing is not available, then symptom descriptions and a series of physical tests are useful.

Diagnosing CTS, however, is not straightforward. Only a small fraction of patients exhibit all three factors necessary for a clear diagnosis:

Classic CTS symptoms
Specific physical findings
Abnormal electrodiagnostic test results

Many people have abnormal electrodiagnostic test results without classic symptoms or any symptoms at all. Furthermore, about 15% of the population has symptoms consistent with CTS, but most do not show test results indicating the disorder. In fact, in a 2001 study, some patients who had symptoms, but whose nerve and physical tests were normal, still experienced relief after CTS surgery.

Many cases of CTS are a combination of a medical problem exacerbated by repetitive stress factors at work. The patient should give the doctor a detailed history and description of any complaints, in any part of the body. The patient should report in detail any daily activities that require repetitive hand or wrist actions, abnormal postures, or other regular situations that could affect the nerves in the neck, shoulders, and hands. The patient should report whether the symptoms are more likely to appear at night, or after particular tasks.

Questionnaires. The use of specific questionnaires that score results are quite accurate in assessing the severity of the condition.

Hand Diagram. A diagram of the hand and wrist, usually divided into six regions, is a very useful diagnostic tool. Patients are asked to indicate where their symptoms are, including pain, numbness, or tingling, by locating the affected areas on the diagram. They may also be asked to rate the severity of their symptoms. A diagnosis is probable if at least two of fingers 1, 2, or 3 have these symptoms, and if there is pain in or near the wrist. CTS is possible if at least one of these fingers has symptoms. It is unlikely if there are no symptoms in these fingers, the palm, or the wrist.

One of the most important first steps in diagnosing CTS is to rule out any underlying medical disorders that may be contributing to the condition. Experts emphasize the need to fully examine patients presenting with symptoms of CTS. Relying only on CTS symptoms, and personal or work histories may result in the failure to detect (and thus properly treat) underlying medical conditions that could be serious. If the doctor suspects that an underlying medical condition may be exacerbating the symptoms, laboratory tests will be performed. The doctor may take an x-ray, for example, to check for arthritis or fractured bones.

Raynaud's Phenomenon. A diagram of the hand and wrist, usually divided into six regions, is a very useful diagnostic tool. Patients are asked to indicate the location of their symptoms -- including pain, numbness, or tingling -- by locating the affected areas on the diagram. They may also be asked to rate the severity of their symptoms. A diagnosis is probable if at least two of fingers 1, 2, or 3 have these symptoms, and if there is pain in or near the wrist. CTS is possible if at least one of these fingers has symptoms. It is unlikely if there are no symptoms in these fingers, the palm, or the wrist.

Arthritic Conditions. Arthritic conditions, including rheumatoid arthritis, gout, and osteoarthritis, can all cause pain in the hands and fingers that may mimic carpal tunnel disease. The treatment for these conditions, however, is different.

Muscle and Nerve Diseases. Any disease or abnormality that affects the muscles and nerves, including those in the spine, may produce symptoms in the hand that mimic carpal tunnel syndrome.

About 25% of patients with suspected work-related cumulative trauma or repetitive stress disorders have evidence of other conditions that resemble, but are not, carpal tunnel syndrome. A definitive diagnosis is often difficult. Most require treatments similar to those used for CTS: rest, immobilization, steroid injections, and even surgery if conservative management is unsuccessful.


Location	Description
The Median Nerve in Other Locations	Repetitive work can cause pressure on the median nerve in locations other than the wrist and can also affect other nerves in the arm and hand. The branch of the median nerve that runs through the palm of the hand can be damaged directly by repeated pounding or by the use of certain tools requiring a strong grip using the palm, such as needle-nosed pliers. The median nerve can also be pinched in the forearm.
Guyon's Canal Syndrome (Commonly called ulnar tunnel syndrome)	The ulnar nerve can, like the median nerve, can be trapped as a result of repetitive stress. When this nerve is trapped, the condition is sometimes referred to as ulnar tunnel syndrome. It is more correctly known as Guyon's canal syndrome, however, since this is the name of the passage through which the ulnar nerve passes. General symptoms are similar to carpal tunnel syndrome, but patients experience loss of sensation in the ring and little finger and in the outer half of the palm. It can be a separate problem, although it commonly occurs with CTS. In such cases, release surgery for CTS usually also relieves the ulnar nerve entrapment. The ulnar nerve can also be affected at the elbow.
De Quervain's Tenosynovitis	Tenosynovitis is swelling of the slippery covering of the tendons that move the thumb. When it causes pain on the side of the wrist and forearm right below the base of the thumb, it is known as De Quervain's tenosynovitis. (Finklestein's Test may help identify this. Make a fist that encloses the thumb, and bend the wrist sideways and down away from the thumb. If it causes pain, it is likely to be De Quervain's tenosynovitis.) It may be treated with splints or corticosteroid injections. In severe cases release surgery is effective.
Digital Flexor Tenosynovitis (Trigger or Snapping Finger)	Digital flexor tenosynovitis, commonly called trigger or snapping finger, is brought on when a tendon thickens, leaving the finger or thumb in a bent position. This disorder usually occurs when the tendons thicken and form a knot and may arise in those with hypothyroidism, diabetes, gout, rheumatoid arthritis, or connective tissue disorders. It can cause pain and a clicking sound when the trigger finger or thumb is bent and straightened. It can be effectively treated with corticosteroid injections.
Thoracic Outlet Syndrome	Thoracic outlet syndrome is caused by compression of nerves and blood vessels running down the neck into the arm. It can produce symptoms very similar to CTS. Other symptoms may include Raynaud's phenomenon (changes in sensation and temperature in the hand). The compression occurs at the first rib in the front of the shoulder. This may happen after an accident or simply from chronic slouching posture. A doctor may be able to diagnose the condition by detecting diminished blood flow in the arm as the patient raises the affected hand and turns his or her head toward the opposite side. Although the condition is uncommon, a correct diagnosis is important to differentiate it from CTS, since treatments differ. Surgery may be required to relieve pressure on the nerves and blood vessels.

The following findings are helpful in identifying carpal tunnel syndrome:

Less sensitivity to pain where the median nerve runs through to the fingers
Thumb weakness
Inability to tell the difference between one and two sharp points on the fingertips (this is a late sign of carpal tunnel)

Flick Signal. One important and simple test of carpal tunnel is the "flick" signal:

The patient is asked, "What do you do when your symptoms are worse?"
If the patient responds with a motion that resembles shaking a thermometer, then the doctor can strongly suspect carpal tunnel.

Testing for Thumb Weakness. Two questions are useful in determining thumb weakness:

Can the thumb rise up from the plane of the palm?
Can the thumb stretch so that its pad rests on the pad of the little finger pad?

Provocation Tests. Certain tests are conducted to produce symptoms:

Phalen's Test. In Phalen's test, the patient rests the elbows on a table and lets the wrists dangle with fingers pointing down and the backs of the hands pressed together. If symptoms develop within a minute, CTS is indicated. (If the test lasts for more than a minute even patients without CTS may develop symptoms.) This test may be particularly important in determining the severity of CTS and assessing the results of treatment.
Tinel's Sign. In the Tinel's sign test, the doctor taps over the median nerve to produce a tingling or mild shock-sensation.
Pressure Provocation Test. The doctor presses over carpal tunnel for 30 seconds to produce tingling or shock in the median nerve.
Tourniquet Test. This test employs an inflatable cuff that applies pressure over the median nerve to produce tingling or small shocks.
Hand Elevation Test. The patient raises their hand overhead for 2 minutes to produce symptoms of CTS. The test was recently proven to be accurate and may provide useful information when combined with the Tinel's and Phalen's tests.

Electrodiagnostic tests analyze the electric waves of nerves and muscles. These tests can help detect median nerve compression in the carpal tunnel.

Electrodiagnostic tests are the best methods for confirming a diagnosis of CTS at this time. Doctors who perform these tests should be certified by the American Board of Electrodiagnostic Medicine, which uses rigorous standards in qualifying doctors. Specific electrodiagnostic tests, called nerve conduction studies and electromyography, are the most common ones performed:

Nerve Conduction Studies. To perform nerve conduction studies, surface electrodes are first fastened to the hand and wrist. Small electric shocks are then applied to the nerves in the fingers, wrist, and forearm to measure how fast a signal travels through the nerves that control movement and sensation. In suspected cases of CTS, nerve conduction tests can identify over 85% of true carpal tunnel syndrome cases and eliminate 95% of those that are not true CTS. They are less accurate in identifying mild CTS, however. Patients should be sure their practitioners perform tests that compare a number of internal responses -- not just routine testing that records only the responses of muscles located in the palm at the base of the thumb), and those on the second or third fingers.

Nerve conduction tests can also detect causes of symptoms that mimic CTS but should be attributed to other problems, such as pinched nerves in the neck or elbow or thoracic outlet syndrome.

Electromyography. To perform electromyography, a fine, sterile, wire electrode is inserted briefly into a muscle, and the electrical activity is displayed on a viewing screen. Electromyography can be quite painful and is less accurate than nerve conduction. Some experts question, in fact, whether it adds any valuable diagnostic information. They suggest it be limited to unusual cases or when other tests indicate that the condition is aggressive and may increase the risk for rapid, significant injury.
Portable electrodiagnostic testing. Portable electronic devices (such as NC-Stat, Neurosentinel, and the Nervepace digital electroneurometer) are being evaluated for measuring nerve conductivity. They are relatively quick and easy to use on a large scale in an industrial facility. However, the Advancing Association of Neuromuscular and Electrodiagnostic Medicine maintains that these devices are experimental and are not effective substitutes for standard electrodiagnostic studies.

Limitations. Electrodiagnostic studies are not well standardized, and certain conditions can skew the results of either test:

Obesity can slow the speed of electrical conduction.
Anxiety can slow the speed of electrical conduction.
Women and the elderly normally have slower conduction times than younger adult men.
Temperature also affects nerve conduction speed. When undergoing testing, doctors should strictly control room temperature to lessen its impact.

Ruling out other causes is extremely important in order to avoid unnecessary surgery for CTS. Modifications and improvements of these tests are continually being made.

Note: People with abnormal results who have no CTS symptoms are at no higher risk for CTS than those with normal results and no symptoms.

A diagnosis of carpal tunnel syndrome may follow testing the affected hand for numbness, tingling, weakness or pain in specific areas. Muscle and nerve conduction tests may also help affirm or rule out carpal tunnel syndrome.

Ultrasound. Ultrasound imaging, a relatively inexpensive technique that uses sound waves, is showing promise. Studies indicate that it can identify up to 85% of CTS cases, and some suggest it is as effective as electrodiagnostic tests. It may be effective for ruling out other causes of hand pain, such as tendon injuries, tenosynovitis (swelling of the tendon lining), cysts, and blood clots in the median artery (a rare complication that can cause the sudden onset of CTS symptoms). However, results are mixed on its accuracy. Newer color Doppler ultrasound and other technological advances are improving the results achieved with this technique. A 2005 study comparing high-resolution ultrasonography with electromyography found that ultrasonography may be helpful for estimating the symptom severity and problems with nerve conduction.

MRI. Magnetic resonance imaging (MRI), an advanced imaging technique, is being adapted to distinguish weak nerve signals from surrounding tissue, so that eventually it may be able to precisely diagnose CTS. However, studies in 2002 note that it requires special expertise, has limited diagnostic accuracy, and is still too expensive at present for routine use. MRI is accurate in diagnosing carpal tunnel syndrome about 80% of the time, compared to about 85% using electrodiagnostic tests, which remains the preferred method of diagnosis. MRI may be most effective for detecting any internal injuries, tumors, arthritis, or joint damage that might be causing the problem. It may also be valuable in selecting surgical candidates when electrodiagnostic tests produce unusual results or indicate more severe disease than expected. Additionally, an MRI may be useful for evaluating patients if surgery fails to bring relief.

Treatment

It is critical to begin treating early phases of carpal tunnel syndrome before the damage progresses. A conservative approach to CTS, which may include corticosteroid injections and splinting, is the first step in treating this disorder.

Nevertheless, relapse is common, and studies suggest that surgery is a better option for severe CTS. In one study, 89% of patients who had conservative treatments suffered a recurrence of symptoms within a year. Conservative treatments work best in men under 40. They do not work as well in young women. The conservative approach is also most successful in patients with mild carpal tunnel syndrome. Even among these patients, however, one study found that 60% of patients can expect a relapse. Some researchers are reporting better results when specific exercises for carpal tunnel syndrome are added to the program of treatments.

Limiting Movement. If possible, the patient should avoid activities at work or home that may aggravate the syndrome. The affected hand and wrist should be rested for 2 to 6 weeks. This allows the swollen, inflamed tissues to shrink and relieves pressure on the median nerve. If the injury is work related, the worker should ask to see if other jobs are available that will not involve the same actions. Few studies have been conducted on ergonomically designed furniture or equipment, or on frequent rest breaks. However, it is reasonable to ask for these if other work is not available.

Conservative Treatment Approach. In a major analysis, the following conservative approaches were shown to provide symptom relief:

Wrist splints
Corticosteroids (steroids). Injected or short-term oral corticosteroids may be tried if other methods fail.
Yoga. In one study, 8 weeks of regular yoga practice reduced pain significantly more than splinting.
Manual therapy, a type of physical therapy

A major analysis of other conservative approaches found that patients had no significant relief from nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs include common pain relievers such as aspirin and ibuprofen (Advil). The same report also found no benefits from diuretics, magnet therapy, laser acupuncture, vitamin B6, exercise, or chiropractic care. Other approaches being investigated include omega-3 fatty acid supplements and cognitive-behavioral therapy.

Underlying Conditions. It is important to treat any underlying medical condition that might be causing carpal tunnel syndrome. For example, reducing inflammation in rheumatoid arthritis or other forms of inflammatory disorders that directly cause CTS is very helpful.

Hypothyroidism and diabetes are diseases that are associated with an increased risk of CTS. The treatments for such diseases may offer some relief for CTS symptoms. For example, insulin helps nerves heal. A study of patients with CTS and type 2 diabetes found that patients who had an initial steroid injection followed by 7 weekly insulin injections had significantly less pain than those who received sham therapy (placebo). More research is needed on the effects of insulin injections in patients with CTS.

Wrist splints are used to keep the wrist from bending. They are not as beneficial as surgery for patients with moderate to severe CTS, but they appear to be helpful in specific patients. In one study, the best success rates were in patients with mild to moderate nighttime symptoms of less than a year's duration. In selected patients, up to 80% reported fewer symptoms, usually within days of wearing the splint.

Although typically the splint is worn at night or during sports, one 2000 study reported that wearing it full time is most beneficial. (In the study, few patients actually complied with the regimen and wore them full time, but any regular use appeared to improve nerve function and symptoms.) The splint is used for several weeks or months, depending on the severity of the problem, and may be combined with hand and finger exercises. A 2005 study reported that a 6-week course of at-night splinting reduced symptom severity in people with CTS and that the benefits were still evident after 1 year.

Corticosteroid Injections. Corticosteroids (also called steroids) reduce inflammation. If restriction of activities and the use of painkillers are unsuccessful, the doctor may inject a corticosteroid into the carpal tunnel. Some experts recommend them for patients with CTS whose symptoms are intermittent, and there is no evidence of a permanent injury. In CTS, steroid injections (such as cortisone or prednisolone) shrink the swollen tissues and relieve pressure on the nerve. Evidence strongly suggests that they offer relief in more than 75% of CTS patients. It should be noted that the pain may increase for a day or two after the injection, and skin color may change.

A study comparing the benefits of two steroid injections (8 weeks apart) to a single injection in the treatment of CTS found the patients did not significantly benefit from the second shot. One injection is therefore enough to achieve the maximum benefit of this treatment.

Unfortunately, in most cases, steroid injections provide only temporary relief, although studies comparing steroid injection to surgery have produced conflicting results. In a major analysis, after 1 month, injections were no more effective than placebo (sham) injections.

However, a recent analysis compared the effects of local steroid injection versus surgery in patients with new CTS of at least 3 months' duration. Over the short term, local steroid injection was better than surgery for relieving symptoms of CTS. And after 1 year, local steroid injection was as effective as surgery. Another study compared steroid injection with open-release surgery and found that the surgery resulted in better outcomes, but not improved grip strength, in patients with CTS over a 20-week period.

Most doctors limit steroid injections to about three per year, since they can cause complications, such as rupture of tendons, nerve irritation, or more widespread side effects such as hypertension or elevated blood sugar levels.

Low-Dose Oral Corticosteroids. Oral corticosteroids are medicines taken by mouth. Short-term (1 to 2 weeks), low-dose use of corticosteroids may provide long-term relief. People with diabetes should not take oral corticosteroids.

Yoga. Some evidence suggests that yoga practice may be specifically very helpful for carpal tunnel, since yoga postures are designed to stretch, strengthen, and balance upper body joints. In one study, people who practiced yoga for 8 weeks experienced significantly reduced symptoms compared to wrist splints or no treatment at all. Two other small studies also reported improvement in pain relief. Positive effects may take a few weeks of regular practice of at least two sessions a week.

General Exercise Program. Some experts have reported that people who are physically fit, including athletes, joggers, and swimmers, have a lower risk for cumulative trauma disorders. Although there is no evidence that exercise can directly improve CTS, a regular exercise regimen using a combination of aerobic and resistance training techniques strengthens the muscles in the shoulders, arms, and back, helps reduce weight, and improves overall health and well-being. In one 2001 study, CTS patients experienced symptom relief and signs of improved nerve conduction after 10 months of participation in an aerobic exercise program (such improvements appeared to be due to both weight loss and higher oxygen levels in the blood). One study found that most people with CTS felt improvement after two months of physical therapy that included exercises to improve balance and posture. People with any chronic medical condition or with risk factors for heart disease should check with their doctors about an appropriate exercise regimen.

If symptoms subside, the patient may proceed with a supervised program of joint mobilization and hand and wrist strengthening and stretching, usually offered by physical or occupational therapists. Hand and wrist exercises may be most beneficial for patients with mild to moderate disease who are also treated with splints and other conservative measures. Graston Instrument-Assisted Soft-Tissue Mobilization (GISTM) and Soft-Tissue Moblization (STM) techniques have been shown to improve nerve conduction, wrist strength, and wrist motion.

Ultrasound employs high-frequency sound waves directed toward the inflamed area. The sound waves are converted into heat in the deep tissues of the hand, which opens the blood vessels and allows oxygen to be delivered to the injured tissue. A major analysis suggested this approach may be effective when used for seven weeks or more.

Nonsteroidal anti-inflammatory drugs (NSAIDs), which include aspirin and ibuprofen (Advil), are the most common pain relievers used for CTS. They block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. Unfortunately, as with most other medications used for carpal tunnel syndrome, there are few well-conducted studies to determine their role in CTS. To date, there is no evidence that they offer any significant relief, and regular use can have serious side effects.

NSAIDs Used. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to relieve joint pain and inflammation. There are dozens of NSAIDs. The following are the most common:

Over-the-counter NSAIDs include aspirin, ibuprofen (Advil, Nuprin, Motrin IB, Rufen), naproxen (Aleve), and ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), flurbiprofen (Ansaid), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), dexibuprofen (Seractil), and indomethacin (Indocin).

Regular use of even over-the-counter NSAIDs may be hazardous for anyone. Long-term use can cause stomach problems, such as ulcers and bleeding, and possible heart problems. In April 2005, the Food and Drug Administration (FDA) asked drug manufacturers of NSAIDs to include a warning label on their product that alerts users of an increased risk for cardiovascular events and gastrointestinal bleeding. NSAIDS have been associated with the following side effects:

Ulcers and gastrointestinal bleeding are the major danger with long-term use of NSAIDs.
Increased blood pressure -- most NSAIDs appear to pose this risk, with higher risks observed with piroxicam (Feldene), naproxen (Aleve), and indomethacin (Indocin). Sulindac has the smallest effect; aspirin has no risk. People with hypertension, severe vascular disease, kidney, or liver problems, and those taking diuretics, must be closely monitored if they need to take NSAIDs.
Delay in emptying of the stomach -- this could interfere with the actions of other drugs. The elderly are at special risk.
Kidney abnormalities -- these have been reported in people taking NSAIDs, which resolve when the drugs are withdrawn. Report any sudden weight gain or swelling to a doctor. Anyone with kidney disease should avoid these drugs.

Other side effects include:

Dizziness
Tinnitus (ringing in the ear)
Headache
Skin rash
Depression
Confusion or bizarre sensation (in some higher-potency NSAIDs, notably indomethacin)
Possible higher risk for miscarriage (particularly if the NSAID is taken for more than a week or around the time of conception)
There is a slight risk for liver abnormalities.

COX-2 Inhibitors (Coxibs). COX-2 inhibitors block an inflammation-promoting enzyme called COX-2. This class of drugs was initially believed to work as well as traditional NSAIDs, but with fewer stomach problems. However, numerous reports of heart attacks and stroke have prompted the FDA to re-evaluate the risks and benefits of the COX-2s. Rofecoxib (Vioxx) and valdecoxib (Bextra) have been withdrawn from the U.S. market following reports of heart attacks in patients taking the drugs. At the time of this update, Celecoxib (Celebrex) was still available, but labeled with strong warnings and a recommendation that it be prescribed at the lowest possible dose for the shortest duration possible. Patients should ask their doctor whether the drug is appropriate and safe for them.

Ice and Warmth. Ice may provide benefit for acute pain. Some patients have reported that alternating warm and cold soaks have been beneficial. (If hot applications relieve pain, most likely the problem is not caused by CTS but by another condition producing similar symptoms.)

Anesthetic Injections. In some cases, injections of an anesthetic (such as lidocaine) may be helpful. A recent small study compared a painkilling lidocaine patch with a combination lidocaine-steroid injection. The study found the daily use of a 5% lidocaine patch reduced pain as well as the injections. More patients in the patch group reported satisfaction with their treatment. The lidocaine patch is less painful than injections because it is worn on the skin and doesn't require a shot. Doctors noted improvements in 88% of the patients in the patch group, compared with 74% of the patients in the injections group.

Pheresis. The word "pheresis" means to carry. In the case of carpal tunnel, pheresis is a technique being investigated to deliver (to carry) a corticosteroid cream deep within the wrist. One such technique called iontophoresis uses an electrical current, and another called phonophoresis uses ultrasound. One study recently found steroid injections to be superior to iontophoresis and phonophoresis in the treatment of CTS.

Diuretics. Diuretics such as trichlormethiazide reduce fluid in the body. They are sometimes used to treat CTS. However, studies have not reported any significant benefits with these agents.

Low-Level Laser Therapy. Some investigators are working with low-level laser therapy (LLLT), which generates extremely pure light in a single wavelength. The procedure is painless, but studies are mixed on whether it is any more effective than sham treatment. One major analysis reported that laser therapy was more effective over time than steroid injections (although it does not appear to provide much immediate relief.) A 2004 study comparing LLLT with a sham (inactive) therapy reported no significant differences in outcomes between the two groups.

Muscle Stimulation. Two investigative procedures called automated or electrical twitch obtaining intramuscular stimulation (ATOIMS or ETOIMS) are showing promise. ATOIMS uses an automated mechanical device that vibrates the muscle using a tiny pin. (The sensation is described as similar to a mosquito bite.) ETOIMS uses an extremely mild electrical current. They can also be used together. Both approaches cause the muscles to twitch and then relax until the process is completed. Discomfort is minimal. Small studies are reporting some help in relieving a number of conditions that cause chronic pain, including carpal tunnel syndrome.

Traction. Small studies of a hand traction device showed improvement in some patients. The device, called C-TRAC, significantly improved pain, tingling, and numbness in patients who had failed a minimum of 4 months of therapy with conservative treatments such as NSAIDs, night hand splinting, acupuncture, and hand therapy. Patients used the C-TRAC device for 5 minutes three times daily for four weeks, then as needed to maintain long-term improvement.

Many alternative therapies are offered to sufferers of carpal tunnel syndrome and other repetitive stress disorders. Few, however, have any proven benefit. People should carefully educate themselves about how alternative therapies may interact with other medications or impact other medical conditions, and should check with their doctor before trying any of them.

Vitamin B6. Vitamin B6 (pyridoxine) is often used for carpal tunnel syndrome. Studies have not supported its benefits, however, either in oral or cream form. It should also be noted that excessively high doses of vitamin B6 can be toxic and cause nerve damage.

Acupuncture. Acupuncture may be beneficial. New techniques employing painless laser acupuncture may prove to be particularly effective. The National Institutes of Health issued a Consensus Statement on Acupuncture in 1997, which declared this ancient form of treatment useful as a supplement to standard treatment or even as part of a comprehensive management program for CTS.

Chiropractic Therapies. Chiropractic techniques have been useful for some people whose condition is produced by pinched nerves. In one small study, the technique was as effective as medications or wrist splints for relief of pain, though further research is needed.

Magnets. Magnets are a popular but unproven therapy for pain relief. One small study of patients who wore magnets attached to their wrists showed no benefits over those who wore a nonmagnetic placebo (sham) device, although both groups did experience pain relief, perhaps due to a placebo response.

Botulinum toxin type A. Intracarpal injections of botulinum toxin type A (Botox) have been reported to relieve carpal tunnel syndrome in more than half of the small number of patients tested. The product has been safely used to relieve headaches, myofacial pain, and other neuropathic pains.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Several herbal and homeopathic remedies are sold for pain relief. A small 2002 British study suggested that preparations containing arnica, a popular remedy for swelling and bruising, may ease discomfort following surgery for carpal tunnel, but a 2003 study reported no advantages compared to placebo (an inactive substance).

Research indicates that anxiety, depression, and even pain related to CTS can be relieved to some extent with cognitive behavioral therapy. The focus of this therapeutic approach is to change negative thinking about one's ability to manage pain. Cognitive behavioral therapy is particularly helpful in defining and setting limits. It may be expensive and not covered by insurance, although the therapy is usually of short duration, typically six to 20 one-hour sessions, plus homework, which usually includes attempting a task that the patient has avoided because of negative thinking. Even if people cannot afford this type of therapy, support groups for carpal tunnel syndrome and other sufferers of repetitive stress injuries can be very helpful for exchanging information, specific advice, and solace. Stress management techniques can also be useful in dealing with the psychological and emotional issues accompanying these injuries.

Surgery

Every year more than 200,000 people in the US undergo surgeries for carpal tunnel syndrome. Surgery for CTS is among the most common hand surgeries. In various trials, 70 - 90% of patients who underwent surgery were free of nighttime pain afterward.

Although evidence strongly suggests that surgery is more effective than conservative approaches (at least in patients with moderate to severe CTS), the decision about whether to have surgery to correct CTS, and when to have it, is a troubling one for patients. Electrodiagnostic and other tests used to confirm the presence of CTS are not very useful in determining the best candidates for surgery. For example, results suggesting severe CTS may not relate at all to surgical success or the lack of it.

In general, patients with the following characteristics are less likely to respond to conservative treatment and, therefore, might benefit from surgery:

Older than 50 years of age
Symptoms lasting 10 months or longer
Continual numbness
Muscles in the base of the palm have begun to shrink
Symptoms occur within 30 seconds during a Phalen's test

According to a 2002 study, if none of these factors are present, conservative therapies (splinting and anti-inflammatory agents) are effective in two thirds of patients. However, the conservative approach was ineffective in 60% of patients if only one of these factors were present, in 83% with only two of them, and in virtually all patients who had three or more.

Surgery does not cure all patients, and because it permanently cuts the carpal ligament, some wrist strength is often lost. A number of experts believe that release surgery is performed too often. They recommend aggressive conservative treatment (such as splints, anti-inflammatory agents, and physical therapy) before choosing the more invasive option (surgery). Nevertheless, other experts argue that CTS is often progressive and will worsen over time without surgery. Furthermore, evidence now shows that surgery is better than splints and conservative measures for the relief of pain. Factors that may increase the chances for successful surgery:

Having surgery performed within 3 years of the diagnosis of the disorder
Being in good general health
Having very slow nerve conduction results, but also having some muscle strength before surgery
Symptoms are worse at night than during the day

Factors that may reduce the chances for success:

Being elderly may affect the chances of successful surgery. However, a study found that the majority of patients over age 65 who had surgery were either completely or very satisfied.
Having very severe symptoms before surgery may reduce the chance for successful surgery.
Performing heavy manual labor, particularly working with vibrating tools, may lead to a less successful surgery. Medical evidence has found that only slightly more than half the people who used vibrating hand-held tools were symptom-free 3 years after a CTS operation.
Having very poor nerve conduction results before surgery may reduce the chance for successful surgery. However, some patients with severe symptoms who have normal neurological and physical test results, could still experience significant relief from CTS surgeries.
Patients who are on hemodialysis have good initial success, but approximately half deteriorate in about a year and a half.
Alcohol abuse can negatively affect the results of CTS surgery.
Poor mental health can lead to less successful surgery.
Patients with diabetes and high blood pressure may be more likely to require a second operation.

Factors that make no difference in results:

Patients whose CTS is due to nerve damage from medical conditions, such as diabetes, rheumatoid arthritis, or hypothyroidism. Such patients appear to have the same outcome as those without such conditions, and such disorders should not preclude them from surgery.

Open Release Surgery. Traditionally, surgery for CTS entails an open surgical procedure performed in an outpatient facility. In this procedure, the carpal ligament is cut free (released) from the median nerve. The pressure on the median nerve is therefore relieved. The surgery is straightforward.

In treating carpal tunnel syndrome, surgery may be required to release the compressed median nerve. The open release procedure involves simply cutting the transverse carpal ligament.

The Mini-Open Approach. In recent years, more surgeons have adopted a "mini" open -- also called short-incision -- procedure. This surgery requires only a one-inch incision, but it still allows a direct view of the area (unlike endoscopy, which is viewed on a monitor). The mini-open approach may allow for quicker recovery while avoiding some of the complications of endoscopy, although few studies have investigated its benefits and risks. In a 2005 report, the mini-open approach was directly compared with open release surgery. The recovery time in patients receiving the mini-open approach was shorter than with the open approach, and results were about the same 30 months after the surgery.

Endoscopy. Endoscopy for carpal tunnel syndrome is a less invasive procedure than standard open release.

A surgeon makes one or two 1/2-inch incisions in the wrist and palm, and inserts one or two endoscopes (pencil-thin tubes).
The surgeon then inserts a tiny camera and a knife through the lighted tubes.
While observing the underside of the carpal ligament on a screen, the surgeon cuts the ligament to free the compressed median nerve.

Patients report less pain than those who had the open release procedure, and return to normal activities in about half the time. Nevertheless, at this time the best evidence available does not show any significant long-term advantages of endoscopy over open release in terms of muscle or grip strength or dexterity. The endoscopic approach may even carry a slightly higher risk of pain afterward. This may be due to a more limited view of the hand with endoscopy. (In the open release procedure, the surgeon has a full view of the structures in the hand.) One report indicated a nearly 3-fold increased risk of reversible nerve injury with endoscopic carpal tunnel release, compared with open carpal tunnel release. On the other hand, a recently published review of 486 patients, who had a total of 753 endoscopic release procedures, showed an extremely low number of complications following the procedure. This study calls into the question the widely held belief that endoscopy carries a higher risk of complications. The study also noted that 90% of the patients returned to their original line of work.

Timing for Recovery. Patients should expect the following course:

For some patients, release surgery relieves CTS symptoms of numbness and tingling immediately.

People who have the operation on both hands are completely incapacitated for about two weeks and must have someone to help them at home.
Returning to strenuous work right after surgery may cause the symptoms to return. Patients generally stay out of work for at least a month and often much longer, depending upon the type of surgery and severity of the condition. Recovery time appears to be faster with endoscopy than with open release.
Immediately after surgery patients usually experience a decline in grip strength and dexterity. Studies have reported a wide range of recovery in this area. In one study, grip and pinch strengths reached better levels than before surgery within 6 weeks. In another study, however, grip strength and dexterity did not return to before-surgery levels until 25 weeks after open surgery. The scar may remain tender for up to a year.
Peak improvement (the best level of improvement a patient can reach) may take a long time; in one study, it took an average of almost 10 months.

Physical Therapy. Physical therapy is very important to help rebuild wrist strength. While physical therapy does not reduce the recurrence (return) of symptoms or improve the long-term benefits of surgery, it does accelerate recovery after surgery. Hand exercises can help restore circulation, muscle strength, and joint flexibility in the hand and wrist. Wearing a splint to immobilize the wrist after surgery has no benefits.

Treatment failure and complication rates of CTS surgery vary.

Complications after surgery may include the following:

Nerve damage with tingling and numbness (usually temporary)
Infection
Scarring
Pain
Stiffness. Loss of some wrist strength is a complication that affects between 10% and a third of patients. Endoscopy may have better results than open release. Some patients who have jobs requiring significant strength of the hand and wrist may not be able to perform them after surgery. Such workers may also have problems in other parts of the upper body, including elbows and shoulders. These problems do not go away with surgery and can persist. Studies indicate that between 10 - 15% of patients change jobs after a CTS operation.

If pain and symptoms return, the release procedure may be repeated.

Reasons for procedure failure include:

Incomplete release of the ligament
Extensive scarring
Recurrence of the disorder due to underlying medical conditions

Patients who had open release surgery appear more likely to require repeat operations compared with those who have had endoscopic surgery.

Neurolysis. In severe cases or when scarring is extensive after surgery, surgeons may choose to sever the nerves that are responsible for the pain, using a procedure called external or internal neurolysis. The procedure may extend recovery time substantially, and the need for repeat surgeries may be higher in those who undergo the procedure. One report indicated that neurolysis should be considered if there has not been any recovery within 3 months after surgery, after which improvement is unlikely. It is unclear if this approach offers any benefits over conservative measures to free the nerve from surrounding scar tissue.

Implants. In another procedure for recurrent carpal tunnel syndrome, doctors may take muscle flaps or even fatty tissue from other parts of the body and implant them at the site of the nerve injury. Such flaps enhance the development of new blood vessels, provide padding, and possibly serve as a bed for nerve regrowth. These implants may be used with or without cutting the nerve. Another procedure called vein wrapping uses grafts taken from veins to help protect the scarred nerves.

Resources

www.aanem.org -- Advancing Association of Neuromuscular and Electrodiagnostic Medicine
www.apta.org -- American Physical Therapy Association
www.aoec.org -- The Association of Occupational and Environmental Clinics
www.aaos.org -- American Academy of Orthopaedic Surgeons
www.assh.org -- American Society for Surgery of the Hand
www.ampainsoc.org -- American Pain Society
www.iasp-pain.org -- Association for the Study of Pain
www.aan.com -- American Academy of Neurology
www.nih.gov/niams -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.nlm.nih.gov/medlineplus/carpaltunnelsyndrome.html -- Information on CTS
www.cdc.gov/niosh/homepage.html -- National Institute for Occupational Safety and Health
www.workerscompensationinsurance.com -- Resources for injured workers
www.keybowl.com -- orbiTouch keyboard
www.ergodevices.com -- Hand and wrist support keyboard

References

Tsai CP, Liu CY, Lin KP, Wang KC. Efficacy of botulinum toxin type a in the relief of carpal tunnel syndrome: A preliminary experience. Clin Drug Investig.2006;26:511-515.

Burke J, Buchberger DJ, Carey-Loughmani MT, et al. A pilot study comparing two manual therapy interventions for carpal tunnel syndrome. J Manipulative Physiol Ther.2007;30:50-61.

Hemminki K, Li X, Sundquist K. Familial risks for nerve, nerve root and plexus disorders in siblings based on hospitalizations in Sweden. J Epidemiol Community Health. 2007;61:80-84.

Porrata H, Porrata A, Sosner J. New carpal ligament traction device for the treatment of carpal tunnel syndrome unreposnive to conservative therapy. J Hand Ther. 2007;20:20-28.

Review Date:
3/14/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Glaucoma

FitSugar — Wed, 08 Oct 2008 17:35:34 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Outlook
Risk Factors
Diagnosis
Treatment
Medications
Surgery
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

Bimatoprost (Lumigan) has been approved as a first-line treatment for open-angle glaucoma.

Glaucoma Cases Increasing Worldwide

About 60 million people worldwide will have glaucoma by 2010, and the number will increase to nearly 80 million by 2010, according to a recent study in the British Journal of Ophthalmology.

Weightlifting May Increase Glaucoma Risk

Weightlifting can cause a temporary increase in intraocular eye pressure (IOP), and holding your breath while lifting weights further increases IOP, suggests a 2006 study in the Archives of Ophthalmology. Doctors should ask patients with normal-tension glaucoma if they engage in weightlifting exercise.

IOP and Posture

IOP increases in some people when they are lying prone during sleep, yet glaucoma exams measure IOP in patients while they are sitting upright and awake, notes a 2006 study in the Archives of Ophthalmology. The researchers caution that posture may affect the interpretation of IOP readings.

Pregnancy and Glaucoma

The course of glaucoma is unpredictable during pregnancy -- IOP may remain stable in some women and increase in others, indicates a 2006 study. Although glaucoma eye drops can increase the risk of some pregnancy problems, especially during the first trimester, some pregnant women may need to continue to take glaucoma medication. Be sure your ophthalmologist carefully evaluates your individual case and explains the risks and benefits of taking medication during pregnancy.

Diabetes and Glaucoma

Type 2 diabetes increases the risk for open-angle glaucoma (the most common type of glaucoma). People with type 2 diabetes need to get regular glaucoma screenings.

Glaucoma Surgery

Tube shunts may work better than trabulectomy surgery for some patients with glaucoma, suggests a 2007 study.
Phacoviscocanalostomy, a surgery procedure that combines phacoemulsification (used for cataract surgery) and viscocanalostomy (used for glaucoma surgery), is safe and effective for patients who have both glaucoma and cataracts, indicates a 2006 study.

Introduction

Glaucoma is defined as a disease of the optic nerve, in which the nerve cells in the front of the optic nerve (the ganglion cells) die. The process is irreversible. Previously, it was believed that glaucoma was almost always due to increased intraocular pressure. However, glaucoma has been observed in many patients with normal and even low eye pressure, so the definition now rests on the damage to the optic nerve.

The Aqueous Humor. In understanding of glaucoma, it is important to first consider aqueous humor, the clear, watery fluid that circulates continuously through the front (anterior) chamber of the healthy eye and is a primary focus of glaucoma research. (This fluid is not related to tears, nor is it the dense jelly-like substance called vitreous humor that is contained in the rear chamber.) It serves two important functions in the eye:

It nourishes the area around the colored iris and behind the cornea.
It exerts pressure to help maintain the eye’s shape.

Draining the Fluid and Intraocular Pressure. The aqueous fluid is continuously produced within the front of the eye, causing pressure known as intraocular pressure (IOP). To offset the in-flowing fluid and to maintain normal IOP, the fluid drains out between the iris and cornea (an area known as the drainage angle). It does so through two channels within this angle:

The trabecular meshwork, a sponge-like, porous network, and its connecting passageways are referred to as the "conventional" outflow pathway. Most of the eye fluid outflow occurs in this region and flows from the trabecular meshwork to a group of vessels encircling the anterior chamber, called Schlemm's canal. From here, the fluid enters collection chambers and then flows out into the general blood circulatory system of the body.
The uveoscleral pathway is located behind the trabecular meshwork and is called the "unconventional" pathway. Up to 30% of the fluid flows out through this channel.

Intraocular Eye Pressure. Previously, it was believed that glaucoma was almost always due to an abnormal rise in intraocular pressure.

Glaucoma is a condition of increased fluid pressure inside the eye. The increased pressure causes compression of the retina and the optic nerve which can eventually lead to nerve damage. Glaucoma can cause partial vision loss, with blindness as a possible eventual outcome.

Increased IOP is, indeed, present in most cases of glaucoma, but some patients have normal IOP, which is usually maintained at measurements of 10 - 20 mm Hg. Measurements above this, however, do not necessarily predict glaucoma. For example, only about 10% of people with IOP levels between 21 - 30 mm Hg will actually develop glaucoma. This still puts such individuals at considerable risk for glaucoma, however.

Most people with glaucoma have the form called primary-open-angle glaucoma (also called chronic open-angle glaucoma). Open-angle glaucoma is essentially a plumbing problem.

The disease process may occur as follows:

The drainage angle remains open, but tiny drainage channels in the trabecular meshwork pathway become clogged. This pathway is responsible for most aqueous humor fluid outflow. An imbalance then occurs as fluid continues to be produced but does not drain out efficiently. Experts have still not definitely determined the precise area in the pathway where the blockage is most likely to occur. (In rare instances the pressure is high because the eye produces too much aqueous humor.)
The fluid in the eye’s anterior chamber builds up and increases pressure within the eye. This is called intraocular pressure (IOP).
The intraocular pressure exerts force on the optic nerve at the back of the eye.
Over time, the persistent pressure or other factors irreversibly damages the delicate long fibers of the optic nerve, called axons, which convey images to the brain.
As these axons die, the small cup-like head of the optic nerve may eventually collapse into an enlarged irregular shape.

Optic nerve damage is the basic glaucoma condition. If it is untreated, eventually the nerve deteriorates until a person loses sight, first in the peripheral vision (the vision in the "corner of the eyes"). If it becomes severe, the person loses central vision (in the middle of the eyes), and may eventually become blind. (Blindness is fortunately nearly always preventable with early treatment.)

Primary open-angle glaucoma tends to start in one eye but eventually involves both. In about half of patients the damage in the eye is diffuse, that is the nerve damage is generalized. In the other half the disease is localized, causing wedge-shaped abnormalities in the nerve fiber layers of the retina.

Intraocular eye pressure is normal (between 12 - 22 mmHg) in about 25 - 30% of U.S. glaucoma cases, a condition known as normal-tension glaucoma. (In Japan, the rates may be as high as 70%.) Other factors are present that cause optic nerve damage but do not affect IOP.

Closed-angle glaucoma (also called angle-closure glaucoma) is responsible for 15% of all cases. It is less common than open-angle glaucoma in the U.S., but it constitutes about half of the world's glaucoma cases because of its higher prevalence among Asians. The iris is pushed against the lens, sometimes sticking to it, closing off the drainage angle. This can occur very suddenly, resulting in an immediate rise in pressure. It often occurs in genetically susceptible people when the pupil shrinks suddenly. Closed-angle glaucoma can also be chronic and gradual, a less common condition.

Congenital glaucoma, in which the eye's drainage canals fail to develop correctly, is present from birth. It is very rare, occurring in about 1 in 10,000 newborns. This may be an inherited condition and often can be corrected with microsurgery.

The Light-Processing Parts. To understand sight, one begins with light and its passage through the eye's sensitive camera-like structures:

Light first passes through the cornea, a clear tissue at the front of the eye.
Behind the cornea, the iris (the colored tissues of the eye) opens and closes like a camera shutter to regulate the passage of light.
The lens, located behind the iris, focuses the light, which then hits the retina.
The retina is an electric fragile membrane of nerve cells called photoreceptors that receive light and translate it into signals.
A layer of cells, called the retinal ganglia, receive signals from the retina. These nerve cells are the front ends of the optic nerve cable, which, in turn, receive the signals.
The optic nerve is actually a cable of about 1.2 million nerve fibers called axons. It carries the signals to the brain, which interprets them as images.
They exit the eye through the optic disc, located in the back of the eye.

The Supportive Chambers. To help support and protect these sensitive structures, the eye contains two fluid-filled chambers:

The posterior (rear) chamber is the large area behind the iris.
Fluid passes from the posterior into the anterior (forward) chamber located in the bulging area between the iris and the front of the eye.

Causes

No single factor has been identified as a cause of primary open-angle glaucoma. A number of conditions, alone or in combination, are needed to trigger the processes leading to pressure in the first place and then to the nerve damage that destroys sight. The damage done to the optic nerve in glaucoma is triggered in most cases by the excessive pressure on the optic nerve that, over time, causes damage. Because optic nerve damage occurs in patients with normal as well as high intraocular pressure, however, researchers are investigating several other abnormal events that occur and can damage the optic nerve.

A number of genes have now been identified as possible factors in many cases of glaucoma. A gene called MYOC is of particular interest. Defects in this gene occur in between 3 - 6% of patients with adult-onset and juvenile open-angle glaucoma. They appear to overproduce a sticky protein called myocilin, which clogs the trabecular meshwork. The genes WDR36 and OPTN may cause primary open-angle glaucoma. Researchers hope that identification of genes will help improve screening of high-risk patients.

Specific syndromes have been identified with glaucoma. Many have an inherited component, although in most cases other factors must be present to activate the disease process.

Pseudoexfoliation Syndrome. Pseudoexfoliation (PEX) syndrome (also known as exfoliation syndrome) is the most common identifiable condition associated with glaucoma. In one study, 9% of patients with open-angle glaucoma had the syndrome. PEX occurs when dandruff-like matter flakes off the outer layer of the lens and collects in the drainage angle. The substance is composed of proteins produced by the lens, iris, and other parts of the eye. People can have this condition and not develop glaucoma, but they are at high risk. In one Australian study, 14% of the people with this condition had glaucoma compared to 2% of those without exfoliation. PEX has a strong genetic component but other factors (possibly sunlight, an autoimmune response, or slow virus) may be needed to trigger the disease.

Pigment Glaucoma. Pigment glaucoma starts with a condition called pigment dispersion syndrome, an inherited condition in which granules of pigment (the substance that colors the iris) flakes off into the intraocular fluid. In about 30% of cases, these fragments clog the trabecular meshwork and pressure builds up, causing glaucoma. In one study, 2% of patients had this form of glaucoma.

Irido Corneal Endothelia Syndrome. In irido corneal endothelial syndrome (ICE), cells on the back surface of the cornea spread to the drainage angle, sometimes forming scars that connect the iris to the cornea.

Neovascular Glaucoma. Neovascular glaucoma is always associated with other disorders, usually diabetes, that result in abnormal formation of new blood vessels on the iris and in the drainage system.

Aniridia. Aniridia is a rare inherited disorder (in which the iris is abnormal and increases the risk for glaucoma) that is difficult to treat. (A surgical approach called goniosurgery may help prevent glaucoma in young people with aniridia.)

Congenital Glaucoma. When an infant is born with glaucoma (congenital glaucoma), it is usually caused by an inherited abnormality in the drainage canal. Researchers have identified the gene responsible for 85% of these cases.

A natural process called apoptosis (cellular self-destruction) may contribute to damage in the retinal ganglion nerve cells, the nerve cells that are the front line of the optic nerve. Cell death can occur with or without elevated eye pressure. It is not clear what triggers apoptosis and cell death in such cases, but there are a number of suspects.

Excess Glutamate. Researchers have observed abnormally high levels of glutamate in people and animals with glaucoma. Glutamate is an amino acid that excites nerve cells. In the eye this occurs during vision. Some experts theorize that in glaucoma, either reduced blood flow or increased pressure on nerve cells triggers the release of excess glutamate. In large amounts, glutamate causes the nerve cells to fire intensively, which eventually destroys them.

Reduced Blood Flow. Researchers have observed reduced blood flow to the optic nerve in patients with glaucoma associated with both high and normal IOP. Less blood flow suggests oxygen loss, which may play a role in the destructive process. Some studies suggest that the greatest risk factor for nerve damage in patients is when blood pressure to the eye drops during the night. Ocular pressure at this time is highest, so the risk for nerve damage becomes intensified. Of interest in this regard are reports finding a significant reduction in eye blood pressure at night in patients with normal-tension glaucoma.

Excess Nitric Oxide. Elevated levels of nitric oxide, another nerve-stimulating compound, also plays a role in the nerve-damaging process. Nitric oxide is critical for nerve function and flexible blood vessels, but excess amounts may be toxic to nerves.

Glaucoma and Alzheimer's Disease. Some research has pointed out similarities in the process leading to cell death in glaucoma and Alzheimer's disease. Specifically, in both diseases activation of certain enzymes called caspases occurs and leads to accumulation of fragments of beta amyloid, an insoluble protein that forms sticky patches.

Autoimmunity. Some experts are studying the possibility that normal tension glaucoma may be an autoimmune disease; that is, factors in the immune system, including antibodies, attack cells in the person's own body as if they were foreign substances. In the case of glaucoma, such antibodies would damage parts of the optic nerve.

H. pylori Infection. Some research indicates that glaucoma is associated with Helicobacter (H.) pylori, the bacterium implicated as a major cause of peptic ulcers. Studies have reported over 87% of patients with glaucoma are infected with this bacterium.

People with acute closed-angle glaucoma often have a structural defect that causes a narrow angle between the iris and cornea where the aqueous humor circulates. Conditions that suddenly dilate the pupils may cause this shallow angle to close and precipitate attacks of acute glaucoma in susceptible people. Such conditions may include:

Certain drugs such as antihistamines, tricyclic antidepressants, some asthma medications (nebulized ipratropium), some anti-seizure drugs (topiramate)
Darkness
Emotional stress

When intraocular pressure leading to glaucoma is caused by other diseases or conditions, it is known as secondary glaucoma. Secondary glaucoma may be chronic or acute, mild or severe.

Medical Conditions. A number of diseases can contribute to the development of intraocular pressure leading to glaucoma:

Diseases that affect blood flow to the optic nerve (diabetes, high blood pressure, migraine; people with type 2 diabetes should be regularly screened for glaucoma.)
Hypothyroidism
Sleep apnea
Physical injury in the eye
Extreme nearsightedness (myopia)
Previous eye surgery
Other disorders, including leukemia, sickle cell anemia, and some forms of arthritis

Corticosteroids. Corticosteroids, commonly called steroids, have multiple effects on the trabecular meshwork and may even cause genetic changes. In fact, studying the effects of steroids on the eye is helping researchers understand the glaucoma disease process. Steroids pose a higher or lower risk depending on the form:

Taking topical steroid treatments in the eye poses the highest risk. It must be monitored carefully since, in some cases, damage may be permanent.
Taking oral corticosteroids, particularly in high doses or for long periods, increases the chance of glaucoma. In such cases, the eye disorder typically develops almost immediately and reverses within 2 weeks after the drug has been withdrawn.
Inhaled steroids were not thought to cause glaucoma, but there is some risk in people with a family history of glaucoma and other risk factors.

Symptoms

Chronic glaucoma is insidious. If the pressure increases slowly, it will not produce any symptoms until it has done irreversible damage. In such cases, people may notice visual problems at first only when light is dim. Patients are often sensitive to glare. Eventually they may lose contrast sensitivity; that is, they might have trouble differentiating between varying shades and brightness.

In acute closed-angle glaucoma, the pressure inside the eye increases quickly, and the symptoms are dramatic. Intense pain in the eyebrow area and blurred vision develop usually in one eye, and the patient often feels like the eye will burst (although it won't). The eye usually reddens. A person may see rainbow-like halos around lights. Sometimes nausea and vomiting occur. These symptoms may occur on and off and not appear as a full attack. In either case, they indicate a medical emergency. In chronic closed-angle glaucoma, the process is gradual and painless.

Although congenital glaucoma is usually present at birth, symptoms generally don’t develop in the infant for a few months. If parents notice that an infant’s eyes are enlarging, becoming cloudy, often watering, or tending to close in the presence of light, they should have an ophthalmologist examine the child’s eyes. Port-wine stains on an infant’s face could indicate the Sturge-Weber syndrome, a disorder that occasionally causes glaucoma.

Outlook

Worldwide, glaucoma ranks as one of the leading causes of blindness. Even if people with glaucoma do not become blind, vision can be impaired. In developed countries, most people get treatment in time to preserve their vision. Even so, glaucoma causes between 3 - 6% of blindness cases in Caucasians, and even more cases in African Americans.

In a 20-year study of Caucasian patients with glaucoma, blindness in at least one eye occurred in 27% of patients and blindness in both eyes occurred in 9% of patients. The blindness rates in African Americans are most likely higher. In fact, glaucoma is the leading cause of blindness in African Americans. Despite this higher prevalence, this ethnic group receives surgical treatment at half the rate of Caucasians.

The Process Leading to Vision Loss. Chronic glaucoma is often called “the silent thief of sight," because the afflicted person has no warning sign, no hint that anything is wrong. Untreated, the destruction develops slowly over time:

Over years or decades, the increased pressure compresses nerves at the back of the eyes.
Glaucoma gradually destroys first the outer fibers of the optic nerve, which reduces peripheral vision (the top, sides, and bottom areas of vision), but not central vision.
By the time a person notices that peripheral vision has been lost, permanent damage has already occurred.
If the eye pressure remains high, the destruction can progress until tunnel vision develops, and the person is only able to see objects that are straight ahead.
The last nerve fibers destroyed are those responsible for central vision; if this occurs, the glaucoma victim becomes totally blind.

Although there is no cure for open-angle glaucoma, a number of treatments are available that lower intraocular pressure and slow progression of vision loss.

Risk Factors for Vision Loss. Estimates of progression rates in vision deterioration range from 9 - 30% over a 2 - 7 year period.

According to a study on patients with elevated IOP, for every 1-mm Hg increase in IOP, there is a 10% higher risk of disease progression. A very elevated IOP (above 30 mm Hg) is certainly hazardous. An elevated IOP that is below 30 mm Hg, however, is not necessarily the most important factor in determining the risk for disease progression. Some evidence suggests that frequent and large daily fluctuations in intraocular pressure, not simply high IOP, are associated with the greatest risk for loss of vision. Having normal-tension glaucoma with optic nerve damage also carries a high risk for progression, even if eye pressure is reduced.

In any case, factors other than IOP play a role in increasing the chances for progression and vision loss in patients with slightly elevated IOP and normal tension glaucoma:

Both eyes affected
Pseudoexfoliation (PEX) syndrome. PEX occurs when proteins produced in the eye flake off the outer layer of the lens and collects in the drainage angle.
Bleeding in a specific region called the peripapillary nerve fiber layer
Thin corneas. (People who have thick corneas and elevated IOP may only need to be monitored if they have no other risk factor for vision loss.)
Larger cup-to-optic disc ratio. (The cup of the optic disc is the center portion, which enlarges as nerve damage progresses.)

Non-eye related factors associated with disease progression include being elderly, African American, female, or having a history of migraines.

Acute closed-angle glaucoma is a medical emergency; if the high pressure is not reduced within hours, it may permanently damage vision. Anyone who experiences its symptoms should immediately contact an ophthalmologist or go to a hospital emergency room.

Risk Factors

About 2 million Americans have open-angle glaucoma, but an exact count is unclear. Experts estimate that by 2010, over 60 million people worldwide will have glaucoma, with 74% of these cases due to open-angle glaucoma. Half of people with glaucoma are unaware of this problem because the condition causes no symptoms.

Elevated intraocular pressure in the eye occurs in 5 - 10 million Americans, but only about 10% of such people develop glaucoma because of this pressure. And, in 15% of actual glaucoma cases, IOP is normal. Major studies are helping to clarify the people who are at highest risk for glaucoma and optic nerve damage, including those with normal tension glaucoma.

Elderly. The prevalence of chronic glaucoma increases with age. In a major study, 0.6% of people age 60 - 64 had primary open-angle glaucoma. Among people who were 10 years older, the prevalence had more than doubled to 1.3%, and among those who were age 80 - 84, it had more than doubled again to 3%.

People of African Descent. Across all age groups, according to a 2000 report, the prevalence of glaucoma in African Americans is about 3.5% compared to about 1% in Caucasians. In addition, U.S. studies suggest that glaucoma develops earlier in African American population groups (starting at age 45 instead of age 60 in Caucasians). And, their risk for blindness once they have glaucoma is 14 - 17 times that of Caucasians with glaucoma. African American men are at higher risk than women. African American children who are extremely near-sighted and have relatives with glaucoma should begin regular eye examinations for glaucoma as early as possible.

In a major glaucoma study in Barbados, where most people are of African descent, over 10% of those age 50 and older had open angle glaucoma, and over 15% were afflicted after age 70. About half of the cases had normal or lower eye pressure. An interesting 2001 study suggested that African Americans tend to have significantly thinner central corneas than Caucasians. This could lead to misleadingly lower pressure scores in African American patients who actually may have high IOPs.

Family History. Glaucoma tends to run in families. Brothers and sisters of patients with open angle glaucoma are 5 times more likely to develop glaucoma by the time they are 70 years old than people whose siblings do not have the disease. Previous studies have also found that people with family histories of glaucoma are more likely to already have some vision loss when they are first diagnosed with glaucoma.

Effects of Blood Pressure. The association between a person's blood pressure and intraocular pressure in the eye is not entirely clear. A number of studies have found a higher risk for glaucoma in people with high blood pressure. A 2002 study suggested, however, that people with blood pressure that is low relative to their intraocular pressure may be at higher risk for glaucoma. The same study found no higher risk for glaucoma in people with hypertension, and in fact, high blood pressure was associated with a lower risk.

Having Certain Medical Disorders. Individuals with certain medical or physical conditions, including diabetes, migraine, nearsightedness, and sleep apnea, appear to have a higher risk. Conditions that require the use of any oral or inhaled steroid, particularly high doses for prolonged periods of time, can cause glaucoma. Previous eye surgery also puts people at risk.

Weightlifting. According to a 2006 study, holding your breath while weightlifting can increase the risk for developing normal-tension glaucoma. Weightlifting causes temporary increases in eye pressure; holding your breath during this exercise leads to even greater intraocular pressure.

Risk Factors for Closed-Angle Glaucoma. Chronic closed-angle glaucoma tends to be more common in people of Asian and African descent. Those who have this condition are often extremely farsighted. Acute closed-angle glaucoma occurs much more frequently in women than in men.

Risk Factors for Normal Tension Glaucoma. Risk factors for normal tension glaucoma include Japanese ancestry and a family history of the disease. It is more common in women than in men. A family history of cardiovascular disease also increases the risk.

Risk Factors for Pigmentary Glaucoma. Pigmentary glaucoma occurs three times more often in men then in women and at a younger age.

Risk Factors for Irido Corneal Endothelial Syndrome. This condition occurs more often in light-skinned women.

Diagnosis

A diagnosis of glaucoma no longer simply relies on the presence of pressure within the eye. It requires that there be optic nerve damage or a strong suggestion of damage, which can be clearly seen during a dilated eye examination of the optic nerve. In general, the hallmark sign of this condition is a loss of peripheral vision. With peripheral vision loss, a person can see in front of him- or herself but has lost the vision to the side.

The optic nerve carries the information of vision from the eye to the brain.

Because chronic glaucoma has no warning symptoms, half of its victims are unaware that they have the condition. Early diagnosis, however, is the key to successful treatment of glaucoma. One study reported that the more years since the last visit to an eye professional, the greater the risk for having visual loss.

Everyone over age 65 and African Americans over 40 years old should have periodic eye exams, including tests for glaucoma, every other year.
African Americans between ages 20 - 39 should have eye examinations every 3 - 5 years.
Other people at higher risk (people with diabetes, history of eye injuries, a family history of glaucoma, or those taking corticosteroid medications) should have eye examinations every year after age 35.
People with known glaucoma should have frequent examinations to check peripheral vision and to be sure treatment is maintaining a safe eye pressure. After such examinations, the ophthalmologist will assess current treatment and make necessary adjustments.

Doctors determine the intraocular pressure (IOP) of the aqueous humor inside the eye using tonometry, which measures the force necessary to make an indentation in the eye. There are several methods:

In the Schiotz method, the doctor first anesthetizes the eye with drops, then presses very lightly against it with tonometer, a tiny smooth instrument that is used to measure the pressure.
In the applanation method, the doctor touches a strip of orange-dyed paper to the side of the eye. The stain helps with the examination and rinses out with tearing. The doctor uses a slit-lamp, which is moved forward toward the patient's face until the tonometer touches the eye.
The noncontact approach applies a puff of air and measures the force needed to indent the eye.

Attempting to close the eyelids during the test can increase eye pressure and produce errors in the results.

In general, normal IOP is usually maintained at measurements of 10 - 20 mm Hg. Glaucoma pressure over 21 mm Hg indicates a potential problem. The test is not completely accurate, however. Only about 10% of people with IOP levels between 21 - 30 mm Hg will actually develop glaucoma and optic nerve damage. On the other hand, many people with glaucoma have normal pressure, at least for part of the time.

Changes in posture may also affect IOP. A 2006 study indicated that IOP increases during sleep or when a person is lying down. As IOP tests are generally given in a doctor’s office when a patient is sitting up, they may not provide a completely accurate evaluation of eye pressure.

The cornea thickness may be an important indicator of disease progression in patients with elevated IOP. According to some research, patients with thinner corneas have a significant risk for developing damage from glaucoma, while those with thicker corneas have a low risk.

In order to determine early damage in the optic nerve, a number of diagnostic instruments have been developed to assess the nerve fiber layers at the back of the eye (the fundus) and to check for optic disk cupping. (The cup of the optic disc is the center portion, which enlarges as nerve damage progresses.) The two most common procedures for identifying nerve damage are ophthalmoscopy and fundus photography. Other instruments have been developed, including those that use laser technology and computers, but none have proved to be infallible. No test has proven to be completely accurate, however, and none is routinely performed by all eye professionals.

In order to be accurate, the tests require a skilled professional and there are certain common factors:

The pupils must also be widely dilated using eye drops before the procedure.
Even mild cataracts and a slightly less-than-optimally dilated pupil can degrade the results. Such conditions are common in elderly people, who are the most likely to develop glaucoma.
If the back of the eye is lightly pigmented (colored), the area under observation is less distinct.
If the glaucoma is diffuse and there is a generalized loss of nerve fiber (which occurs in half of patients), it is more difficult to detect than if the glaucoma is more localized.

If IOP is low or normal and tests report optic nerve damage and peripheral visual loss, doctors should also check for other conditions before starting any treatment for glaucoma. Such problems include steroid use, anemia, and previous hemorrhage or severe low blood pressure.

Ophthalmoscopy. The eye professional (or even a primary care doctor) uses an ophthalmoscope to peer through the pupil directly at the optic nerve. The examiner can then check the shape and color of the nerve fibers to evaluate whether they have been damaged by the high pressure of glaucoma. Damaged nerve fibers may be indicated by:

An asymmetrical or elongated cupped optic nerve
The optic nerve color may be pale or an unhealthy-pink

If results show no optic nerve damage in patients who have mild elevations in pressure, the ophthalmologist may want to retest frequently but delay drug treatment, unless the patient has significant risk factors.

Fundus Photography. Fundus photography may be used to take pictures of the optic nerve and can reveal changes years in advance of vision loss. It is an unpleasant procedure requiring drops and a bright flash. This procedure has the same limitations as ophthalmoscopy.

Laser Polarimetry. Polarimetry uses laser technology to scan the eye and does not require any response from the patient. It is reported to be able to measure nerve fiber thickness in the eye and so be able to reveal early signs of deterioration. Preliminary studies have indicated that it has a diagnostic accuracy of over 90% for both confirming and ruling out glaucoma. One study, however, reported that laser polarimetry was sensitive enough to detect glaucoma in only up to 57% of patients with early glaucoma, 71% of those with moderate disease, and 81% of those with severe glaucoma. More research is needed.

Other Devices. Computer-assisted devices, such as the confocal scanning laser ophthalmoscope, are now available that may be useful for evaluating the retinal nerve layer. Another instrument, the optical coherence tomograph, measures the echo time delay of light that is scattered back from different layers in the retina. The value of these tests has not yet been determined.

If there is indication of optic nerve damage, the eye professional will conduct tests of the visual fields (the areas that the patient can see). In most people with glaucoma, the first areas to become noticeably impaired are the peripheral visual fields (areas of sight that are not directly in front of a person but more to the sides).

Click the icon to see an image of the visual field test.

Standard Perimetry Tests. Perimetry tests are used to check peripheral vision. One variation of this test is as follows:

A person sits closely facing a large computer-like monitor.
Small bright white lights flicker on and off hundreds of times, at different places on the screen, while the patient clicks a button whenever one of the lights is seen.
The machine prints out a report that maps any blanked-out areas in the person’s vision.

The test is complex and lengthy; elderly people and those with short attention spans may be inappropriate candidates. Other perimetry tests, some requiring less time to administer and some using "virtual reality" techniques, are currently being developed.

Other Tests. Other visual field tests are being developed that can detect abnormalities years before they can be detected by standard perimetry. Experts recommend some of these tests in selected patients with suspected glaucoma.

For example, a screening test called frequency doubling technology (FDT) checks for changes in particular cells in the retina that are indications of early glaucoma. It takes less than a minute to perform.

Another test called short wave automated perimetry (SWAP) uses colors (blue-on-yellow) and also detects very early abnormalities in the visual field. Testing time is longer than with FDT, however, and the presence of certain types of cataracts can interfere with its accuracy.

ELAM-1. Endothelial leukocyte cell adhesion molecule 1 (ELAM-1) is a molecule that has been found in glaucoma but not in healthy eyes. This molecule may prove to be a "marker" and its presence may be helpful in diagnosing glaucoma.

A simple test using a penlight helps determine the risk for acute closed-angle glaucoma. A beam of light is directed from the side of the face toward the patient's iris. If no shadow appears on the nose, then most likely the angle is wide enough to dilate. Using an instrument called a gonioscope, ophthalmologists can also inspect the front of the eyes and assess the drainage angle between the cornea and the iris and the channels in the trabecular meshwork. This test can differentiate between closed- and open-angle glaucoma.

Treatment

Most treatments for glaucoma aim to reduce ocular pressure and its fluctuations. Early treatment with medications, surgery, or both can nearly always maintain safe pressure of the aqueous humor, thus preventing optic nerve damage and blindness. The choice between surgery and medications and when to start treatment is not always straightforward. For example, with the introduction of beta blockers and newer glaucoma drugs, there has been a decline in surgeries. It is not clear, however, which drugs are more effective than others and if, over time, any will actually prevent surgery. Patients should discuss all issues with their doctors and ophthalmologists.

Many people have high IOP but no sign of nerve damage. Over the course of 20 years, only between 10 - 30% of these people will actually develop glaucoma. Nevertheless, once glaucoma has destroyed optic nerve fibers, no known treatment can reverse the damage.

Indeed, studies suggest that in people with glaucoma, even very small differences in pressure may mean the difference between disease progression and stability. An important trial reported that, on average, treating patients when their glaucoma was first detected reduced IOP by 25%. In addition, treatment reduced the risk for progression by 17%. This study confirmed previous findings supporting early treatment for glaucoma. Another study found that treatment with eye drops halved the risk of developing open-angle glaucoma in African Americans who had elevated IOP. Some evidence suggests that early treatment to lower IOP may be beneficial even in patients with normal tension glaucoma.

However, not all individuals with early signs of glaucoma (elevated IOP or normal-tension glaucoma) develop optic nerve damage and serious vision problems. Nor does treatment prevent progression in a large minority of patients. Medications used for glaucoma also can carry significant side effects and risks.

Some experts suggest that treatment is warranted only in people with early signs of glaucoma who have risk factors for progressive disease and vision loss (thinner corneas, larger cup to optic disc ration, older age, and elevated pressure).

A number of effective drugs are now available for treating glaucoma. The drugs reduce pressure in the eye but all have a number of side effects that affect other parts of the body. Some of these side effects can be quite severe. Many of the drugs used for glaucoma also interact with common medications for other conditions. To compound the difficulties, many patients require multiple drugs. As a result, only about half of patients comply with their treatments.

Experts generally recommend topical drugs first (those that can be used as eye drops or ointments rather than taken by mouth).

Topical beta blockers are the standard first-line drugs, most commonly timolol (Timoptic). Newer beta blockers include betaxolol (Betoptic), levobunolol (Betagan), carteolol (Ocupress), and metipranolol (OptiPranolol). Timolol has been used for years, and these other drugs are also well tolerated.
Topical prostaglandins are alternatives if beta blockers fail. They include latanoprost (Xalatan) and unoprostone (Rescula). Of the standard drugs used for glaucoma, these drugs have the greatest effect on lowering IOPs. They also have fewer widespread effects than the beta blockers.
Topical carbonic anhydrase inhibitors (CAIs) are less effective than standard beta blockers or prostaglandins but have fewer widespread effects than the beta blockers. They may be helpful in certain cases. Topical forms are dorzolamide (Trusopt) and brinzolamide (Azopt). (Oral CAIs are available and more effective, but they have severe side effects and are rarely used for the long term.)
Alpha2-adrenergics, also called selective alpha adrenergics, are effective but may not be as well tolerated as timolol. They include brimonidine (Alphagan).
Miotics, which include pilocarpine and others, were the standard drugs before the introduction of topical beta blockers. They have now been largely replaced by timolol and others, although they are sometimes used in combinations.
Beta blockers and newer drugs (prostaglandins, topical CAIs, and selective alpha adrenergics) are now preferred over the older drugs, which include miotics, oral CAIs, and nonselective alpha adrenergics.

Combinations. Combinations of these drugs can be very effective, because they tend to have different actions. Single medications that contain two drugs are becoming available. For example, Cosopt combines timolol and dorzolamide; Timpilo is a combination of timolol and pilocarpine. Studies of these and other combinations compared to each other to single drugs are ongoing. To date, results on any superior combinations have been mixed. It should be noted that the side effects of each drug apply to any combination.

Treating the Pregnant Patient. Considerations for a pregnant woman with glaucoma can be complicated. All of the drugs used for glaucoma are absorbed by the body, cross the placenta, and are excreted in breast milk. Many have effects that can interfere with or adversely affect pregnancy.

Women should discuss going off medication, particularly during the first trimester, and be monitored during that time for increasing eye pressure. IOP tends to drop during pregnancy, although usually not to a significant degree. In addition, changes in IOP and visual loss vary greatly. Some women experience no IOP change or visual loss during pregnancy, while others may experience an increase in IOP or worsening of visual loss. It is important that your ophthalmologist carefully considers your individual case and discusses with you the risks and benefits of continuing glaucoma medication during pregnancy.

If women need to take medications, they should try to achieve the lowest dose possible. Some drugs have fewer side effects than others. Pregnant women must also be very careful about administering eye drops to allow as little medication as possible to enter the body. When taking eye drops, press your index finger against the corner of the eye near your nose. This helps prevent the eye drop from passing down into the tear duct where it is easily absorbed through the rest of the body. Even this approach, however, does not guarantee complete safety. Women with glaucoma who are planning to become pregnant might want to consider surgery before they conceive.

The object of standard glaucoma surgery is to reduce pressure in the eye by increasing the outflow of the aqueous fluid. Two methods are commonly used:

Filtration surgery (trabeculectomy). This uses standard surgical instruments to open a passage in the eye for draining fluid.
Laser trabeculoplasty. This procedure uses a laser to burn 80 - 100 tiny holes in the drainage area.

Both are effective, but certain patient groups may respond to one more than the other. For example, African Americans may do better with laser surgery while trabeculectomy may be a better choice for Caucasians with no serious medical problems.

In general, surgery is a last resort. Doctors may, however, recommend surgery before drug therapies for patients unlikely to comply with difficult drug regimens or for patients who may have severe reactions from the glaucoma drugs. Women who plan on becoming pregnant should also discuss surgery with their doctor.

Some studies indicate that laser treatment performed as the initial treatment for glaucoma is as effective as medications in some cases. Findings in 2003 from a major comparison study suggested that 4 years after surgery there was little difference in visual field loss between trabeculectomy and medical treatment. There was, however, a higher risk for cataracts and loss of vision sharpness with surgery. On the other hand, side effects from medications may be ongoing and troublesome. It is important to note that even surgery does not cure glaucoma, and over half of patients will require medication within 2 years. Experts who are against early surgeries also argue that studies on their success often omitted serious postoperative problems, such as late-onset infection, and quality of life assessments.

Medications

Nearly all glaucoma medications are prescribed for reducing eye pressure. Lowering IOP is even proving to be beneficial for about two-thirds of patients with normal-pressure glaucoma.

Topical beta adrenoceptor blockers (common called beta-blockers) are the drugs most often prescribed to treat glaucoma. They lower the pressure inside the eye by inhibiting the production of aqueous humor.

Brands. These drugs are categorized as either nonselective or selective beta-blockers:

Nonselective adrenoceptor beta-blockers. Timolol (Timoptic, Betimol) has been the standard beta-blocker for years. Newer nonselective drugs include levobunolol (Betagan), carteolol (Ocupress), and metipranolol (OptiPranolol). A few studies suggest some are more beneficial than timolol with similar side effects.
Selective beta1-adrenoceptor blockers. Betaxolol (Betoptic) and levobetaxolol (Betaxon) are selective beta-blockers. These drugs appear to have fewer adverse effects on the heart than the nonselective beta-blockers, although they still have widespread effects. Studies also suggest that they slow progression more than timolol, although timolol is more effective at lowering IOP. selective beta-blockers may also have nerve-protecting properties.

All beta-blockers are effective and generally well tolerated. Because they cause less eye irritation than many other glaucoma medications, they are often prescribed for patients who also have cataracts.

Side Effects and Complications. After the beta-blocker is administered, only a tiny amount of the drug is absorbed by the cornea. Most of it enters in the bloodstream. These drugs, therefore, can cause side effects in parts of the body other than the eyes ("systemic" side effects):

Common systemic side effects include reduced sexual drive, fatigue, depression, anxiety, severe nausea and vomiting, and breathing difficulties.
Beta-blockers affect the heart. They lower heart rate and reduce blood pressure. (The newer selective beta-1 blockers may not have as bad effects on the heart as the nonselective beta-blockers.) They may also cause unhealthy cholesterol and triglyceride changes.
All beta-blockers can worsen severe asthma or other lung diseases. Beta-blockers should only be used very cautiously or not at all by anyone with asthma, emphysema, bronchitis, or heart disease. In one study, lung function was reduced in 40% of elderly people who took timolol, even those without previous symptoms of lung problems. (Selective beta-blockers may produce fewer of these adverse effects.)
If the patient is switching to a beta-blocker from other glaucoma medication, there may be a sudden rise in eye pressure. It is important that the pressure be checked shortly after the other drug has been withdrawn.
When beta-blockers are used to treat one eye, the other (contralateral) eye also experiences a lesser, but still significant reduction in IOP.

Interactions with Other Medications. The effects of the eye medication may be additive to other oral medications, such as oral beta-blockers, calcium-channel blockers, or the antiarrhythmic drug quinidine. People with diabetes who take insulin or hypoglycemic medications should realize that timolol side effects may resemble and mask the symptoms of hypoglycemia (low blood sugar).

Prostaglandins are hormone-like substances that help open blood vessels. Drugs that resemble prostaglandins increase outflow of aqueous humor (the watery substance in the eye). Drainage of aqueous humor helps reduce intraocular pressure.

Brands. Latanoprost (Xalatan) and unoprostone (Rescula) are the standard brands. Latanoprost was the first prostaglandin to be approved as first-line treatment for elevated eye pressure. Two newer prostaglandins, travoprost (Travatan) and bimatoprost (Lumigan), may help some patients who do not respond to latanoprost. These drugs may also benefit patients with normal-tension glaucoma. Latanoprost, travoprost, and bimatoprost need to be taken only once daily. Unoprostone needs to be taken twice a day and is not as effective as others, but it still can reduce IOP significantly and is the least expensive of these drugs.

Latanoprost has been shown to reduce pressure by between 45 - 70%. Some, but not all studies, have suggested that newer prostaglandins travoprost (Travatan) and bimatoprost (Lumigan) are more effective than latanoprost, but the older drug appears to be better tolerated. All of these drugs may be work better than timolol in lowering IOP. The newer prostaglandins may be especially superior to timolol in treating African American patients. In comparison studies, latanoprost achieved better IOP pressure reduction than brimonidine. Studies have suggested that bimatoprost is more effective in lowering eye pressure than a combination of timolol and dorzolamide (Cosopt). Studies have been mixed on whether latanoprost is superior to the combination.

Side Effects. These drugs do not slow down the heart rate and also appear to be safe for people with asthma. Side effects include itching, redness, and burning during administration. Muscle and joint pain may also occur. All of these drugs may permanently change eye color from blue or green to brown. To date, such color changes do not seem to be hazardous. (The only significant problem may be cosmetic in people who treat only one eye, since the color may differ from the other.) These drugs can increase blood flow in the eye and also make eyelashes become thicker and longer in some patients. (These latter effects are more common with bimatoprost and travoprost than with latanoprost.)

Carbonic anhydrase inhibitors (CAIs) decrease eye pressure by reducing the fluid in the chambers of the eye (aqueous humor). Research suggests that CAIs reduce aqueous humor fluid by as much as 40%. These drugs are used for glaucoma when other drugs do not work. They may be combined with other medications.

CAIs may also improve blood flow in the retina and optic nerve (beta-blockers do not). Improving blood flow can keep the disease from getting worse.

Brands and Side Effects. CAIs are available in the following forms:

Eye-drop CAIs include dorzolamide (Trusopt) and brinzolamide (Azopt). About 10% of patients report fatigue, stinging in the eye, and loss of appetite using dorzolamide. Taste changes can occur. Research suggests that dorzolamide can be helpful for children with glaucoma, including those younger than 6 years old. Brinzolamide is a newer medication that was chemically designed to be closer in pH to human tears and may cause less stinging than dorzolamide.
Oral forms include acetazolamide (Diamox), methazolamide (Neptazane), and dichlorphenamide (Daranide). Although they are more effective than eye drops, they have significantly more side effects and are rarely used for long-term treatment. The oral forms have very unpleasant side effects that include frequent urination, depression, stomach problems, fatigue, weight loss, sexual dysfunction, and, in infants, failure to thrive. Long-term use of the oral forms, in rare cases, can cause serious anemia and kidney problems, including the risk for stones. They can also produce a toxic reaction when taken with large doses of aspirin.

Adrenergic agonists activate muscles in the eye that dilate pupils and, therefore, increase outflow of aqueous fluid. Newer variations called alpha 2-adrenergic agonists reduce production of aqueous humor and also increase outflow through the uveoscleral pathway (the alternative channel to the trabecular meshwork). Older adrenergic agonists include epinephrine.

Alpha 2-Adrenergic Agonists. Apraclonidine (Iopidine) and brimonidine (Alphagan) are alpha 2-adrenergic agonists. These have generally been used before glaucoma surgery, but a number of studies are indicating that they may even be useful as primary therapy when used in combination with beta-blockers or other standard drugs.

Brimonidine is proving to be particularly effective for long-term therapy. (Apraclonidine is used for the short term.) It also may have nerve-protecting properties and may be safer than other drugs during pregnancy and for patients with asthma.

The most common side effects of brimonidine and apraclonidine are dry mouth and altered taste. They also commonly trigger an allergic reaction that causes red and itching eyes and lids, a major drawback. Brimonidine causes less of an allergic response than apraclonidine. Unlike apraclonidine, however, it can cause lethargy and mild low blood pressure. It also appears to remain effective longer.

Miotics, also called cholinergic agonists, narrow the iris muscles and constrict the pupil. This action pulls the iris away from the trabecular meshwork and allows the aqueous humor to flow out through the drainage channels, reducing the pressure inside the front of the eye.

Brands. Pilocarpine (Pilocar, Adsorbocarpine, Almocarpine, Isoptocarpine, Ocusert) was the most widely used anti-glaucoma drug before timolol was introduced. It is the preferred miotic. Because pilocarpine is used up by the body fairly quickly, however, patients must take it several times a day; many people, therefore, fail to take their medication regularly. A combination of timolol or latanoprost with pilocarpine is more effective than either drug used alone. Carbachol is another miotic.

Demecarium (Humorsol), isoflurophate (Floropryl), and echothiophate (Phospholine) are a group of long-acting drugs known as anticholinesterase miotics. Because of their potential for serious side effects, however, some authorities even prefer surgery to their use.

Epinephrine and its derivatives are the older anticholinergics. Epinephrine is now rarely prescribed because of side effects. Dipivefrin (Dipivefrin), a newer form of epinephrine, remains inactive until it reacts with enzymes in the cornea. It is effective in low doses and causes few systemic side effects.

Side Effects. Side effects include:

Teary eyes, brow-aches, eye pain, and allergic reactions.
A miotic narrows the pupil and so can cause nearsightedness. Vision can also become dim and it may difficult to see in darkened rooms or at night, when driving could be hazardous. A gel form administered once a day or wafer placed under the lid once a week may help reduce these side effects.
The anticholinesterase miotics increase the risk of cataract development and are therefore used mostly in patients in whom cataracts have already been removed. Retinal detachment is an uncommon but dangerous side effect in susceptible individuals. Excessive use of these miotics may cause toxic reactions, including convulsions, muscular paralysis, and even death from respiratory failure.
Epinephrine can produce burning in the eyes, enlarged pupils, and allergic reactions. Occasionally it can cause anxiety and headaches. Rare side effects include high blood pressure and disturbances in heart rhythm. It is rarely prescribed now. Although dipivefrin, the newer form of epinephrine, has fewer systemic side effects, it still causes problems in the eyes similar to those of epinephrine.

Cannabinoids. Cannabinoids, compounds in marijuana (cannabis), are being studied for their effects on glaucoma. For example, oral or inhaled tetrahydrocannabinol (THC), the active ingredient in marijuana, has been shown to reduce IOP in 60 - 65% of patients. The effects of smoking marijuana on IOP last only 3 hours, however. THC also increases the release of glutamate -- a nerve-protecting chemical. Experts are hoping that topical use of THC or other cannabinoids may help prevent optic nerve damage without the widespread effects of oral or inhaled administration.

Reasons for Noncompliance. Studies indicate that more than 40% of patients miss 10% of their doses, and 15% of patients miss more than 50% of their doses. Noncompliance is very high for many reasons:

People with chronic glaucoma who are on medication must use eye drops or take pills one or more times a day, usually for the rest of their lives.
Many people require a multi-drug regimen, two or more different kinds of medications that can be used in various combinations, such as eye drops, ointments, or time-release wafers inserted under the eyelid. Such regimens can be very confusing.
The side effects of the drugs are more unpleasant than the disease itself, which has no symptoms until vision is lost. Because the treatment does not usually produce any noticeable improvement, the consequence of not taking the drugs (blindness) may seem far in the future.
Skipping even a few doses can greatly increase the risk of visual loss. It is essential that patients tell their doctor if they are not regularly taking their medication. Otherwise, the doctor may increase the dosage, thereby causing unwelcome side effects.

Patients who do not regularly take their glaucoma medication are at high risk for blindness. If you have problems taking your medications or sticking to the dosing regimen, talk with your doctor.

Hints for Managing a Regimen.

Pharmaceutical manufacturers use colored tops, yellow for timolol, for example, and green for pilocarpine, to help prevent mix-ups. Creating a chart scheduling each drug by color can be helpful.
Small electronic timers are available that will signal times for taking the medications. The timing of these combinations is important. For example, the combination of pilocarpine with latanoprost is most effective when pilocarpine is taken four times a day and when the bedtime dose is administered an hour after latanoprost.
Some patients may be candidates for single medications that combine two drugs, such as Cosopt, which contains both dorzolamide and timolol. This medication requires only one drop twice per day. Patients who need additional glaucoma drugs, however, will need to take these two drugs separately.
When using any drug for a long period of time, side effects are a potential problem. If they become intolerable, patients should discuss with the doctor reducing the dosage or trying other drugs.

Administering Eye Drops. A common reason that medicine does not work is that patients do not take it correctly. Patients should ask the ophthalmologist to watch while they place the drops in their own eyes to make sure the procedure is being done correctly. The following are some recommended steps:

If you use both ointments and eye drops, take the eye drops first.
Wash your hands before applying eye drops.
Hold the bottle upside down.
Tilt your head back and, with one hand, pull the lower eyelid down to form a pocket.
With your other hand, hold the bottle as close as possible to your eye. Don’t let the bottle directly touch your eye or eyelid.
After you have placed the drop, close your eye or press your index finger against the corner of the eye near your nose. Gently move the lower lid upward until the eye is closed. Keep your eye closed for at least 1 minute. This prevents the drop from draining out.
Wait at least 5 minutes before applying another drop or a different medication

In this emergency situation, ophthalmologists may administer a combination of two or more anti-glaucoma medications to reduce eye pressure quickly before it can damage the optic nerve and cause visual loss. Apraclonidine (Iopidine) is a powerful drug used before and after laser surgery to prevent an increase in fluid pressure and is more effective than other medications. In addition to standard drugs, doctors may also administer glycerin (Glyrol, Osmoglyn) by mouth or mannitol or acetazolamide intravenously. Surgery is almost always performed once the pressure is reduced.

Most rare forms of glaucoma respond to the same medications and surgery used for open angle glaucoma. Irido corneal endothelial syndrome (ICE) is difficult to treat and if surgery is required, filtering surgery is the best choice. Neovascular glaucoma is also very hard to treat; researchers are investigating drainage implants for this disorder.

Surgery

If medications do not control eye pressure, or if they create intolerable side effects, surgery may be necessary in a small percentage of people with chronic glaucoma. It may be particularly helpful for patients with pseudoexfoliation glaucoma.

The standard procedures are usually one of the following:

Filtration surgery (trabeculectomy). This procedure opens the full thickness of the drainage area.
Laser trabeculoplasty. This procedure partially opens the drainage area. It does not reduce pressure to the extent of trabeculectomy but it has fewer adverse effects.

African Americans may respond better to initial laser surgery than to conventional trabeculectomy, while the opposite may be true in Caucasians. Some experts now recommend that, in most circumstances, African Americans should start with laser surgery and Caucasians who have no serious medical problems should have trabeculectomy first.

In addition, a number of experimental and less invasive procedures are under development.

The Procedure. Filtration surgery has been used for more than 100 years with only minor modifications. It employs conventional surgical techniques known as full-thickness filtering surgery or guarded filtering surgery (trabeculectomy).

The surgeon creates a sclerostomy, a passage in the sclera (the white part of the eye) for draining excess eye fluid.
A flap is created that allows fluid to escape but which does not deflate the eyeball.
The surgeon may also remove a tiny piece of the iris (called an iridectomy) so that fluid can flow backward into the eye.
A small bubble called a bleb nearly always forms over the opening, which is a sign that fluid is draining out. Although surgeons aim for a thick bleb, which poses less risk than a thin one for later leakage, paradoxically the ideal operation would have no bleb at all.

The procedure has a high success rate. About 50% of patients no longer need medication after surgery. Thirty-five to 40% of those who still need medication have better control of their glaucoma.

A new instrument called a trabectome has allowed for a less invasive type of trabulectomy surgery The trabectome procedure appears to be a safe and simple way to lower eye pressure. It can be performed before a traditional trabulectomy, if needed. Results from a small study, presented at the 2005 meeting of the American Academy of Ophthalmology, showed that the new approach successfully reduced eye pressure in 90% of patients with open-angle glaucoma.

Side Effects. Many of the serious side effects or complications that occur with filtration surgery involve blebs (blister-like bumps).

Bleb Leaks and Infections. Blebs, particularly thin ones, commonly leak. Leakage can occur early on or sometimes as late as months or years after surgery. Untreated, such leaks can be serious and even cause blindness. Late-onset leakage significantly increases the risk for infection as well as a number of other serious conditions, including bleeding, a flattening of the eye ball, and harmful inflammation. Surgical repair is the most effective way of managing leaking blebs, although drug therapies, pressure patching, and other nonsurgical techniques may be tried first. Due to the dangers of leaking blebs, experts recommend lifelong monitoring after surgery. Unfortunately, the incidence of late-onset leaking blebs is increasing due to the use of drugs used in filtration surgery to prevent scarring, another complication.
Scarring. In up to 20% of cases, scars form around the incision, closing up the drainage channels and causing pressure to rebuild. These scars are formed from fibroblasts, which are immature collagen cells that form at the surgical site. Scarring is a particular problem in young patients, African Americans, patients who have taken multiple drugs, have had an inflammatory disease, or have had cataract surgery. Releasing the surgical stitches used in the procedure may help prevent scarring and pressure build-up. A second procedure called bleb needling sometimes can open up the scarred area and restore drainage. With this technique, the tip of a very fine hypodermic needle is used carefully to cut loose the particles closing off the drainage area. A new technique that does not require sutures may prove to be effective and have fewer complications.
Cataracts. The procedure is highly associated with the development of cataracts over time. Because cataracts are associated with glaucoma anyway, it is not entirely clear whether the cataracts are caused by the surgery or would develop in any case.

Click the icon to see an illustrated series detailing cataract surgery.

Supportive Medication for Preventing Scarring. Specific drugs, usually mitomycin C, are often used in conjunction with the procedure to prevent scarring and closure. A large review of studies of mitomycin C supported its effectiveness in increasing surgical success in nearly all patients. Fluorouracil (5-FU) appears to be similar in effectiveness but has a high risk for complications and is not used as often as in the past.

The Procedure. Laser trabeculoplasty involves the following steps:

The procedure uses an instrument, usually a YAG laser, to burn 80 - 100 tiny holes in the drainage area.
A tiny scar forms, which increases fluid outflow.
The procedure takes 15 minutes, causes almost no discomfort, and has very few complications.

In a 2-year study, laser surgery of the trabecular meshwork reduced pressure by a third in 70 - 97% of patients. Patients still need to take anti-glaucoma eye drop medications every day.

Laser surgery is not a cure. Within 2 - 5 years, about half of patients need either additional surgery or new medications.

Complications. In about 35% of patients, pressure increases after surgery. In most cases it is temporary, but in rare cases the increased pressure is permanent and vision loss can occur. Use of the drug apraclonidine (Iopidine) or pilocarpine can help prevent this elevated pressure. About a third of patients also develop adhesive-like substances called peripheral anterior synechiae that cause the iris to stick to part of the cornea.

Drainage implants, also known as tube shunts, may be used to drain fluid in certain cases, such as if glaucoma is not responsive to any standard procedure or is caused by certain conditions. A 2007 study suggested that tube shunts work better than filtration surgery (trabulectomy) for some patients. In the study, patients who received tube shunts had more stable IOP over the course of a year than patients who underwent trabulectomy.

Candidates. Success rates are highest (75% pressure control over 5 - 7 years) in appropriate patients. Drainage implants may be useful in the following conditions:

Glaucoma caused by swelling in the iris
Glaucoma caused by abnormal vessel formations
Iridocorneal endothelial (ICE) syndrome

The Procedure. In general, the procedure involves:

An implant, most commonly a 1/2 inch silicone tube, is inserted into the eye's front chamber (anterior). The Molteno implant used with mitomycin C is currently the most effective approach, with reported success rates of 80%. Other implants, such as the Ahmed implant, may have fewer complications.
The tube drains the fluid onto a tiny plate that is sewn to the side of the eye.
Fluid collects on the plate and then is absorbed by the tissues in the eye.

Complications. Complications include:

Hypotony (very low eye pressure) is a serious complication that has been reduced using better techniques and improved implants.
Cataracts, detached retina, breakdown of the cornea, and bleeding are potentially significant complications.
There is also a risk for eye movement disorders, such as strabismus (crossed eyes) or diplopia (double-vision).

The implant often becomes blocked and repeated operations are needed. Some researchers are studying the use of a drug called tissue plasminogen activator (tPA) to open up tubes that have been blocked by blood or blood factors. (This so-called clot-busting drug is normally used to break up blood clots during heart attacks.) In one 2002 study, tPA prevented such blocks in 89% of eyes. Unfortunately, significant complications rates were high (11%).

Deep sclerectomy and viscocanalostomy are less invasive techniques than filtering surgery that leave the anterior chamber (front of the eye) intact and avoid creation of blebs.

In deep sclerectomy, the surgeon removes a deep piece of the sclera (the white part of the eye), part of the trabecular meshwork, and the front of Schlemm's canal (the vessels that return fluid into the bloodstream).

In both deep sclerectomy and viscocanalostomy, the surgeon first creates a flap in the outer part of the sclera (the white part of the eye) and then removes a deep piece of the sclera underneath. This opens up Schlemm's canal (the vessels that return fluid into the bloodstream) and exposes a layer above the anterior chamber called Descemet's membrane. A space has also been created between the inner and outer layers of the sclera.
In deep sclerectomy, this space now serves as a tiny reservoir for aqueous fluid that flows through the membrane and pools here. The fluid then flows out without the surgeon having to open the anterior chamber (as in standard filtering surgery).
In viscocanalostomy, the surgeon typically injects gel-like materials into the ends of Schlemm's canal in order to enlarge the canal for fluid outflow and lower IOP. The tiny reservoir is sewn tightly up.

Many variations are under investigation. In general, the procedures have fewer complications afterward than standard filtering surgery, although they require excellent surgical skill. Nonpenetrating techniques do not lower IOPs as much as conventional surgery does, however. In time, however, these nonpenetrating techniques are expected to be as effective as filtration surgery.

Cataracts and Glaucoma. For patients with both glaucoma and cataracts, experts recommend the following:

In patients with cataracts and poorly controlled glaucoma, a two-step procedure for both eye conditions is needed. Typically the patient will first have a trabeculectomy for glaucoma, followed by cataract surgery such as phacoemulsification (lens removal through ultrasound). Fluid leakage and the presence of blood in the back chamber of the eye are potential complications of this combined procedure.
Phacoemulsification is sometimes combined with viscocanalostomy in a procedure called phacoviscocanalostomy. A 2006 study suggested this approach is safe and effective. The study followed patients for 7 years after they underwent phacoviscocanalostomy and found that no serious complications occurred.
In patients who have cataracts plus either closed-angle glaucoma or open angle glaucoma that is stabilized with medication, the cataract may be able to be extracted and medication continued for the glaucoma.

A major 2002 analysis suggested that the combined approach generally offers better control over eye pressure for patients with both cataracts and glaucoma. However, it is still unclear which specific type of surgical procedure works best. [See In-Depth Report #26: Cataracts.]

Diode laser transscleral cyclophotocoagulation (TSCPC), also called laser cycloablation, reduces aqueous production by destroying the muscles that control the lens for near and far vision (the ciliary body ). There is a chance of vision loss with this procedure, so it is reserved for people with end-stage glaucoma or those who fail to benefit from any other therapies. Nevertheless, researchers continue to explore the possibilities for this effective procedure, especially for people who may not have access to expensive medications. Studies have suggested it may even be suitable as first-line surgery for some patients.

For an acute closed-angle glaucoma attack, emergency microsurgery is usually necessary after reducing pressure with medications.

Iridotomy or Iridectomy. Either laser (iridotomy) or conventional (iridectomy) surgery may be used. With either procedure an ophthalmologist makes a tiny opening in the iris to let the aqueous humor flow out more freely. Because acute glaucoma commonly occurs later in the other eye, surgeons will often recommend surgery in the unaffected eye to prevent a second attack.

Laser iridotomy almost never requires hospitalization, and postsurgical treatment includes only aspirin and eye drops. It has almost completely replaced conventional surgery, which requires anesthesia and hospitalization.

Vision will be blurred, and recovery can take 4 - 8 weeks. Once surgery has been performed, such patients can usually use previously restricted anticholinergic medications, such as antihistamines and certain antidepressants, with safety.

Phacoemulsification and Intraocular Lens Implantation. Phacoemulsification and intraocular lens implantation, a procedure ordinarily used for cataracts, may prove to be beneficial for some patients with acute angle-closure glaucoma requiring surgery. [See In-Depth Report #26: Cataracts.]

Lifestyle Changes

Studies suggest that patients with glaucoma who exercise regularly (at least 3 times a week) may be able to reduce their intraocular pressure by an average of 20%. If they stop exercising for more than 2 weeks, pressure increases again. In one study, those who walked briskly 4 times a week for 40 minutes were able to go off their medications. (Although not confirmed by any evidence, yoga or other exercises that involve head-down or inverted positions may be harmful for patients with glaucoma and should be discussed with the doctor.)

Exercise has no effect on closed-angle glaucoma. It may, in fact, increase eye pressure in patients with pigmentary glaucoma. Vigorous high-impact exercise may cause more pigment to be released from the iris in these patients. Patients should talk to their doctor about an appropriate exercise program.

Antioxidants in Foods and Supplements. Diet most likely plays very little role in glaucoma. For example, a 2003 study found no association between important nutrients associated with protection against other eye disorders, including vitamins C, E, A, and carotenoids.

Caffeine. Some studies have shown that large amounts of caffeine drunk in a short period of time can elevate eye pressure for up to 3 hours. One study suggested that such changes in eye pressure could be significant in patients with both normal eye pressure and high IOP.

Fluids. Drinking large amounts (a quart or more) of any liquid within a short time, about 30 minutes, appears to increase pressure. Patients with glaucoma should have plenty of fluids, but they should drink them in small amounts over the course of a day.

Glaucoma can cause the eyes to be very sensitive to light and glare. Medications can worsen this problem. Sunglasses solve this problem and are important for prevention of cataracts. Protective sunglasses do not have to be expensive. Sunglasses are classified into three categories based on protection against ultraviolet radiation (UV) A or B:

Cosmetic-purpose sunglasses block at least 70% UVB and up to 60% UVA. People should avoid these glasses if they have any risk for cataracts or eye problems.
General-purpose sunglasses block at least 95% UVB and a minimum of 60% UVA. At the very least, people should purchase general purpose sunglasses and they should be labeled "Meets ANSI Z80.3 General Purpose UV Requirements.” Labels should indicate that sunglasses block UV radiation up to 400 nm.
Special-purpose sunglasses block at least 99% UVB and a minimum of 60% UVA rays. These are the optimal sunglasses for people at risk for eye disease. Special purpose glasses should wrap around the head and block light coming from above, below, and both sides of the glasses. They should also fit snugly on the nose.
Lenses that are simply dark but not coated with UV-absorbing material may increase the risk of cataracts because the pupil widens to compensate for the shaded glass. This may allow more harmful ultraviolet waves to enter the eye. Polarized glasses cut glare but have no effect on UV radiation. Mirror finishes without additional processing for UV blockage also are not fully protective. There is some controversy over whether blue light is harmful to the eyes. Some people prefer amber lenses, which block out the blue spectrum.

Meditation, biofeedback, and relaxation methods can help counteract stress, and there are some reports that they may help some people with open-angle glaucoma. A number of herbal and nontraditional remedies have been advertised as glaucoma remedies. A few studies have reported that the herbal remedy ginkgo biloba may have properties that offer benefits to patients with glaucoma, including increasing blood flow in the eye without altering overall blood pressure, heart rate, or intraocular pressure. More research is, however, needed.

The following is of special concern for people with glaucoma:

Bilberry, a European blueberry (Vaccinium myrtillus), is sold in natural food stores as a glaucoma remedy. Studies indicate that it may help some people improve night vision and glare, but it is not at all effective in preventing or treating glaucoma.

Resources

www.glaucoma.org -- Glaucoma Research Foundation
www.nei.nih.gov -- National Eye Institute
www.glaucomafoundation.org -- The Glaucoma Foundation
www.aao.org -- American Academy of Ophthalmology
www.glaucomaweb.org -- American Glaucoma Society
www.lighthouse.org -- Lighthouse International

References

Bottaro M, Ritch R. Intraocular pressure variation during weight lifting. Vieira GM, Oliveira HB, de Andrade DT. Arch Ophthalmol. 2006 Sep;124(9):1251-4.

Brauner SC, Chen TC, Hutchinson BT, Chang MA, Pasquale LR, Grosskreutz CL. The course of glaucoma during pregnancy: a retrospective case series. Arch Ophthalmol. 2006 Aug;124(:1089-94.

Gedde SJ, Schiffman JC, Feuer WJ, Herndon LW, Brandt JD, Budenz DL. Treatment outcomes in the tube versus trabeculectomy study after one year of follow-up. Am J Ophthalmol. 2007 Jan;143(1):9-22.

Hara T, Hara T, Tsuru T. Increase of peak intraocular pressure during sleep in reproduced diurnal changes by posture. Arch Ophthalmol. 2006 Feb;124(2):165-8.

Higginbotham EJ. Managing glaucoma during pregnancy. JAMA. 2006 Sep 13;296(10):1284-5.

Pasquale LR, Kang JH, Manson JE, Willett WC, Rosner BA, Hankinson SE. Prospective study of type 2 diabetes mellitus and risk of primary open-angle glaucoma in women. Ophthalmology. 2006 Jul;113(7):1081-6.

Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006 Mar;90(3):262-7.

Wishart MS, Dagres E. Seven-year follow-up of combined cataract extraction and viscocanalostomy. J Cataract Refract Surg. 2006 Dec;32(12):2043-9.

Review Date:
3/3/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Back pain and sciatica

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Diagnosis
Medications
Complementary and Alternati...
Exercise and Physical Thera...
Surgery
Other Treatments
Specific Treatment for Acut...
Specific Treatment for Chro...
Prognosis
Complications
Prevention
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Surgery

Kyphoplasty, a surgical technique used to treat spinal fractures, does not improve a person's back pain or quality of life, according to a review published in 2006 by a nonprofit health services research agency. Kyphoplasty should only be done if bed rest, medicines, and physical therapy do not relieve back pain.

Ultrasound

Therapeutic ultrasound uses sound waves to deliver gentle vibrations to an area of the body. Scientists in England are studying whether therapeutic ultrasound may help relieve pain and disability due to sciatica.

Acupuncture

Studies continue to show that acupuncture helps some patients with low back pain. Now, research published in the British Medical Journal online says the alternative treatment seems to be worth the price in the long run.

Stem Cells

Researchers in England have pioneered a new technique to grow new spinal tissue using stem cells. Stem cells are the building blocks of specific cells. Every cell in the human body starts (or "stems") from a stem cell. Researchers say a patient's stem cells may someday be used to grow new tissue that can replace damaged discs.

Back pain tied to brain changes

Chronic back pain appears to be linked to tiny structural changes in the brain. German researchers have found that persons with chronic back pain have more activity in the parts of the brain involved in pain processing and emotional responses. It is unclear if the brain changes came before the pain or if they occurred in response to the pain. The scientists presented their findings at the 2006 Radiological Society of North American annual meeting.

Introduction

Back pain is one of the most common reasons people visit their doctor. According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases, 8 out of 10 people have some type of backache.

Back pain can be acute or chronic.

Acute pain develops suddenly and goes away within 6 weeks. Acute pain is the most common type of back pain.
Chronic pain can come on fast or slow, but it lasts longer than 3 months. Back pain can occur in any area of the back, but it is more common in the lower part, which supports most of the body’s weight.

The back is highly complex, and pain may result from damage or injury to any of various bones, nerves, muscles, ligaments, and other structures. Still, despite sophisticated techniques that provide detailed anatomical images of the spine and other tissues, the cause of most cases of back pain remain elusive.

Vertebrae. The spine is a column of small bones, or vertebrae, that support the entire upper body. The column is grouped into three sections.

The cervical (C) vertebrae are the seven spinal bones that support the neck.
The thoracic (T) vertebrae are the twelve spinal bones that connect to the rib cage.
The lumbar (L) vertebrae are the five lowest and largest bones of the spinal column. Most of the body's weight and stress falls on the lumbar vertebrae.

Click the icon to see an image of the spine.

Below the lumbar region is the sacrum, a shield-shaped bony structure that connects with the pelvis at the sacroiliac joints.

At the end of the sacrum are two to four tiny, partially fused vertebrae known as the coccyx or "tail bone."

Click the icon to see an image of the sacrum.

Each vertebra is designated by using a letter and number, which allows the doctor to determine where it is in the spine.

The letter reflects the spinal region where the vertebra is located: C=cervical (neck region), T=thoracic (chest, or middle back, region), and L=lumbar (lower back).
The number signifies the vertebra's place within that spinal region. The numbers start with 1 at the top of a region and count up as the vertebrae descend within the region. For example, C4 is the fourth bone down in the cervical region and T8 is the eighth thoracic vertebrae.

The Disks. Vertebrae in the spinal column are separated from each other by small cushions of cartilage known as intervertebral disks. The disks have no blood supply of their own. They need to rely on nearby blood vessels to keep them nourished.

Click the icon to see an image of an intervertebral disk.

Each disk is 80% water and contains two structures.

Inside each disk is a jelly-like substance called the nucleus pulposus.
The nucleus pulposus is surrounded by a tough, fibrous ring called the annulus.

Click the icon to see an image of the nucleus pulposus.

Processes. Each vertebra in the spine has a number of bony projections called processes. The spinal and transverse processes attach to the muscles in the back and act like little levers, allowing the spine to twist or bend. The particular processes form the joints between the vertebrae themselves, meeting together and interlocking at the zygapophysial joints (more commonly known as facet or z joints ).

Spinal Canal. Each vertebra and its processes surround and protect an arch-shaped central opening. These arches, aligned to run down the spine, form the spinal canal, which encloses the spinal cord.

Click the icon to see an image of the vertebrae and spinal cord.

Spinal Cord. The spinal cord is the central trunk of nerves that connects the brain with the rest of the body. Each nerve root passes from the spinal column to other parts of the body through small openings bounded on one side by the disk and the other by the facets. When the spinal cord reaches the lumbar region, it splits into four bundled strands of nerve roots called the cauda equina (meaning horsetail in Latin).

Click the icon to see an image of the cauda equina.

Causes

In about 85% of back pain cases, the origin of the pain is unknown, and imaging studies usually fail to determine the cause. Disk herniation and disk degeneration due to aging are the most common causes of low back pain. Other problems can also cause this pain, however.

Over the years, the disk can wear away (degenerate), causing inflammation and irritation. This age-related condition is a major source of chronic low back pain.

A herniated disk, sometimes, but incorrectly, called a slipped disk, is widely held to be the most common cause of severe back pain and sciatica. A disk in the lumbar area becomes herniated when it ruptures or thins out and degenerates to the point that the gel within the disk (nucleus pulposus) pushes outward. The damaged disk can take many forms.

A bulge -- The gel has been pushed out slightly from the disk and is evenly distributed around the circumference.
Protrusion -- The gel has pushed out slightly and asymmetrically in different places.
Extrusion -- The gel balloons extensively into the area outside the vertebrae or breaks off from the disk.

There is some debate, however, about how pain develops from a herniated disk and how frequently it causes low back pain. Many people have disks that bulge or protrude and do not suffer back pain. Extrusion (which is less common than the other two conditions) is highly associated with back pain, since the gel is likely to extend out far enough to press against the nerve root, most often the sciatic nerve. Extrusion is very uncommon, however, while sciatic and low-back pain are very common. But there may be other causes of low back pain

Ordinarily, at the time of any injury, the immune system triggers key factors that are designed to promote healing. Evidence is now pointing to an abnormal and persistent immune response in the cells of the nucleus pulposus that may be responsible for nerve injury and pain in the lower back. In such cases, the nucleus pulposus in the herniated disk overproduces certain factors known as cytokines -- notably tumor necrosis factor (TNF) -- that, in high levels, cause inflammation and cell damage. Evidence now suggests that such cytokines cause a biochemical reaction in the regions surrounding the bulging or protruded nucleus pulposus, which results in pain.

Abnormalities in the Annular Ring. Research has also focused on tears in the annular ring -- the fibrous band that surrounds and protects the disk. The annular ring contains a dense nerve network and high levels of peptides that heighten perception of pain. Tears in the annular ring are a frequent finding in patients with degenerative disk disease. Some cases of chronic low back pain may be caused by inward growth of nerve fibers into the annular ring, which triggers pain within the intervertebral disk.

At some time, up to 40% of people have pain called sciatica. This condition occurs when the sciatic nerve is trapped or inflamed.

The Sciatic Nerve. The sciatic nerve has an extensive pathway.

It first branches from the nerve roots that descend off the lowest part of the spinal cord (in the lumbar and sacral areas). Each of the two branches of the sciatic nerve is about as wide as a thumb.
Each branch of the nerve threads through the pelvis and deep into either side of the buttocks.
The nerve branches then pass down each hip and along the back of each thigh to the foot.

Causes of Sciatica. A herniated disk pressing on the sciatic nerve is the most common cause of sciatica, although spinal stenosis or other vertebral abnormalities that press on the sciatic nerve can also cause pain.

The main nerve traveling down the leg is the sciatic nerve. Pain associated with the sciatic nerve usually originates when nerve roots in the spinal cord become compressed or damaged. Symptoms can include tingling, numbness, or pain that radiates to the buttocks, legs, and feet.

Symptoms of Sciatica

Pain due to sciatica can vary widely. It may feel like a mild tingling, dull ache, or a burning sensation. In some cases, the pain is severe enough to cause immobility.

The pain most often occurs on one side. Some people have sharp pain in one part of the leg or hip and numbness in other parts. The affected leg may feel weak.

The pain often starts slowly. Sciatica pain may get worse:

At night
After standing or sitting for long periods of time
When sneezing, coughing, or laughing
After bending backwards or walking more than 50 - 100 yards (particularly if it is caused by spinal stenosis)

Sciatica pain usually goes away within 6 weeks, unless there are serious underlying conditions. Pain that lasts longer than 30 days, or gets worse with sitting, coughing, sneezing, or straining may indicated a longer recovery.

Other than age-related degenerative disk disorders, injuries in the muscles and ligaments supporting the back are the major causes of low back pain. Of note, is the iliac crest pain syndrome (iliolumbar syndrome), in which there are tears in the ligaments that help support the pelvic bone.

Spinal stenosis is the narrowing of the spinal canal. This typically develops as a person ages and the disks become drier and start to shrink. At some point in this process, any disruption, such as a minor injury that results in disk inflammation, can cause impingement on the nerve root and trigger pain. Pain from spinal stenosis can occur in both legs, or it can be felt as sciatica. Spinal stenosis occurs mostly in the elderly with degenerative osteoarthritis, but it can sometimes be caused by other problems, including infection and birth defects.

Spondylosis is a condition in which the fourth or fifth lumbar vertebrae degenerate or develop small fractures. This condition affects 4 - 6% of the general population, and the rates may be higher in certain populations. As it progresses, the spine can become unstable and lead to spondylolisthesis, in which one vertebra slips forward over the other and causes sciatica. The condition most often occurs in older individuals with women having a higher risk than men. It is also a common cause of back pain from stress fractures in young athletes and can also be due to inherited problems, injury, or bone disease.

Some cases of sciatica pain may occur when a muscle located deep in the buttocks pinches the sciatic nerve. This muscle is called the piriformis. The resulting condition is called piriformis syndrome. Piriformis syndrome usually develops after an injury. In rare cases leg swelling, deep-vein blood clots, or both may occur. Piriformis syndrome is sometimes difficult to diagnose.

Ankylosing spondylitis is a chronic inflammation of the spine that may gradually result in a fusion of vertebrae. Symptoms include a slow development of back discomfort, with pain lasting for more than 3 months. The back is usually stiff in the morning; pain improves with exercise. In severe cases, the patient must continually stoop over. It can be quite mild, however, and it rarely affects a person's ability to work. It occurs mostly in young Caucasians in their mid-20s. The disease is more common in men, but about 30% of the cases are in women. Researchers believe that in most cases it is hereditary. About 20% of people with inflammatory bowel disease and about 20% of people with psoriasis develop a form of ankylosing spondylitis. There are few effective treatments for this potentially disabling disease, although etanercept (Enbrel) and infliximab (Remicade), anti-inflammatory agents known as TNF-blockers, are proving to be beneficial.

Any abnormality in joints, vertebrae, or nerve roots can cause back pain:

The facet (z-joints) joints can wear down. In such cases, pain occurs on arching the back or when walking.
In some cases a segment (consisting of two vertebrae and their common joint and disk) becomes unstable when its parts wear down.
Injury to nerve roots, notably deep root ganglia (nerve cells in the spine whose fibers extend from skin to muscle tissue), may be important in some cases. Some patients may have scar tissue that traps the nerve roots in the lower spine and causes sciatica.

Risk Factors

In most known cases, pain begins with an injury, after lifting a heavy object, or after making a sudden movement. Not all people have back pain after such events, however. In the majority of back pain cases, the causes are unknown.

Some evidence suggests that after episodes of back pain, some people may experience changes in brain structure and chemicals that produce an exaggerated response in nerve cells. In fact, a 2005 study suggested that chronic back pain actually shrinks the brain by as much as 11%. Such brain changes may cause a persistent perception of pain even though the actual injury has healed.

German researchers have found that chronic back pain appears to be linked to tiny structural changes in the brain. Using a specialized imaging method, they learned that persons with chronic back pain seemed to have a different, more complex structure to their brain and more activity in the areas involved in pain processing and emotional responses. It is unclear if the brain changes occurred before the pain or in response to the pain.

A number of conditions may make people more or less susceptible to low back pain.

Intervertebral disks begin deteriorating and growing thinner by age 30. One-third of adults over 20 show signs of herniated disks (although only 3% of these disks cause symptoms). As people continue to age and the disks lose moisture and shrink, the risk for spinal stenosis increases. The incidence of low back pain and sciatica increases in women at the time of menopause as they lose bone density. In older adults, osteoporosis and osteoarthritis are also common. However, the risk for low back pain does not mount steadily with ever-increasing age, which suggests that at a certain point, the conditions causing low back pain plateau.

Inherited Spinal Structure Abnormalities. Many people have a genetic susceptibility to low back pain, usually from inheriting spinal structural abnormalities.

Inherited Weakened Disks. Studies are finding that specific mutations of the COL9A gene may play a role in about 10% of sciatica cases. The gene is normally involved in producing collagen, the protein building block in all structural tissue in the body. When defective, it may cause the disk to be less able to resist compressive forces. One 2001 study found the defective gene was present in twice as many patients with disk problems as in patients without back pain.

The likelihood of experiencing back pain increases as children age. Some studies suggest that pain is more common among girls than boys. A common cause of temporary back pain is carrying backpacks that are too heavy for children. Backpacks should not weigh more than 20% of the child's body weight. They should weigh even less for very young children. Emotional or behavioral problems may also contribute to back pain in children.

Jobs that involve lifting, bending, and twisting into awkward positions, as well as those that cause whole-body vibration (usually due to long-distance truck driving), place workers at particular risk for low back pain. The longer a person continues such a job, the higher the risk. Some workers wear back support belts, but evidence strongly suggests that they are useful only for people who are currently have low back pain. The belts offer little added support for the back and do not prevent back injuries. In one study, workers who wore the belt for prevention reported more back pain than the workers who did not wear them.

A number of companies are developing programs to protect against back injuries. Although studies are mixed on the outcome of company interventions, one analysis suggested that they do have a positive effect. Employers and workers should make every effort to create a safe working environment. Office workers should have chairs, desks, and equipment that support the back or help maintain good posture.

Infections. A number of common and uncommon infections are a cause of back pain. Chronic uterine or pelvic infections can cause low back pain in women. Osteomyelitis is infection in the spine, a rare cause of back pain. Other infections that cause back pain include Lyme disease, septic arthritis, bacterial endocarditis, Reiter syndrome, mycobacterial, fungal arthritis, and viral arthritis. Chlamydia pneumonia, an atypical organism that is a common cause of mild pneumonia in young adults, is now believed to cause widespread inflammation in the body's tissue, including blood vessels, and may be responsible for a number of chronic conditions, including heart disease. Some evidence further suggests it may cause inflammation in arteries of the lower spine and contribute to spinal stenosis.

Many medical conditions are associated with back pain.

Osteoporosis is a disease of the skeleton in which the amount of calcium present in the bones slowly decreases to the point where the bones become fragile and prone to fracture. It usually does not cause pain unless the vertebrae collapse suddenly, in which case the pain is often severe. Studies indicate, however, that the incidence of low back pain and sciatica increase around the time of menopause, and very tiny fractures in the vertebrae caused by osteoporosis may be an undetected cause of back pain in many elderly women.
Osteoarthritis occurs in joints where cartilage is damaged and then destroyed, usually as a result of aging. In reaction to this destruction, the bones associated with the joints develop abnormalities. When osteoarthritis affects the spine, it may damage the cartilage in the disks, the moving joints of the spine, or both. The nerves may become pinched, causing pain and in advanced cases, numbness and muscle weakness. The patient may also experience muscle spasms and diminished mobility.
Inflammatory disorders, such as Crohn's disease and rheumatoid arthritis, can produce inflammation in the spine (sacroiliitis), although the spine is less commonly affected than other locations.
Other conditions that can directly cause pain include fibromyalgia, Paget's disease, Parkinson's disease, abscesses, blood clots, and cancer.
Other medical conditions cause referred back pain, which occurs in conjunction with problems in organs unrelated to the spine (although usually located near it). Such conditions include ulcers, kidney disease (including kidney stones), ovarian cysts, and pancreatitis.

Osteoporosis is a condition characterized by progressive loss of bone density, thinning of bone tissue and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency or advanced age. Regular exercise and vitamin and mineral supplements can reduce and even reverse loss of bone density.

It should be noted, however, that a number of medical conditions, such as lung and heart problems and chronic headaches, commonly occur with low back pain. A causal relationship among them, however, is uncertain.

Persistent low back pain in children is more likely to have a serious cause that requires treatment than back pain in adults. According to one small study, one third of children being treated at a hospital for back pain were found to have serious underlying problems.

Stress fractures (spondylolysis) in the spine are a common cause of back pain in young athletes. Sometimes a fracture may not show up for a week or two after an injury. Spondylolysis can cause spondylolisthesis, a condition in which the spine becomes unstable and the vertebrae slip over each other.

Hyperlordosis is an inborn exaggerated inward curve in the lumbar area. Scoliosis, an abnormal curvature of the spine in children, does not usually cause back pain.

Juvenile chronic arthropathy is an inherited form of arthritis. It can cause pain in the sacrum and hip joints of children and young people. It used to be grouped under juvenile rheumatoid arthritis, but is now defined as a separate problem.

Injuries, benign tumors such as osteoblastoma or neurofibroma and cancers, including leukemia, can also cause back pain in children.

Medications may trigger back pain. For example, anticoagulants can cause bleeding or an internal bruise. Long-term steroid use can cause infection or compression fractures.

Some research is suggesting that some people have motor control abnormalities in the deep muscles near the spine. Such lack of control causes instability in the spine that can lead to pain.

Pregnant women are prone to back pain due to a shifting of abdominal organs, the forward redistribution of body weight, and the loosening of ligaments in the pelvic area as the body prepares for delivery. Tall women are at higher risk than short women. Although some earlier research had suggested that the use of epidurals for pain relief during labor could lead to chronic back pain, studies in 2002 reported no increased risk.

Psychological factors are known to play a strong influential role in three phases of low back pain:

Some evidence suggests preexisting depression and the inability to cope may be more likely to predict the onset of pain than physical problems. For example, a British study reported that people who showed emotional distress at age 23 were nearly twice as likely to suffer from back pain 10 years later. A 2005 study found that a “passive” coping style (not wanting to confront problems) was strongly associated with the risk of developing disabling neck or low back pain.
The perception of pain. Social and psychological factors play a role in the severity of a person's perception of back pain. For example, one study compared truck drivers and bus drivers. Nearly all the truck drivers liked their work. Half of them reported low back pain but only 24% lost time at work. Bus drivers, on the other hand, reported much lower job satisfaction than truck drivers, and these workers with back pain had a significantly higher absentee rate than truck drivers in spite of less stress on their backs. Similarly, another study found that pilots, who generally reported "loving their jobs," reported far fewer back problems than their flight crews. And yet another study reported that low rank, low social support, and high stress in soldiers was associated with a higher risk for disabling back pain.
Chronic pain. Depression and a tendency to develop physical complaints in response to stress also increase the likelihood that acute back pain will become a chronic condition. The way a patient perceives and copes with pain at the beginning of an acute attack may actually condition the patient to either recover or develop a chronic condition. Those who over-respond to pain and fear for their long-term outlook tend to feel out of control and become discouraged, increasing their risk for long-term problems.

Studies also suggest that patients who reported prolonged emotional distress have less favorable outcomes after back surgeries. It should be strongly noted that the presence of psychological factors in no way diminishes the reality of the pain and its disabling effects. Recognizing it as a strong player in many cases of low back pain, however, can help determine the full range of treatment options.

Diagnosis

Because nearly all cases of low back pain clear up in a short time and are not due to serious problems, a medical history and a brief physical examination are almost always sufficient.

Still, with very severe or chronic back pain, it is important that any serious medical causes as well as cauda equina syndrome and progressive nerve damage be ruled out first. If the doctor suspects a serious underlying cause, the approach to determining the origin of back pain involves answering three questions:

Is some general medical disorder present that could be causing the pain?
Are there social or emotional factors that might be intensifying the pain?
Are the nerves in the spine involved in the pain (such as in sciatica)?

Such questions can usually be answered with a medical history and physical examination.

A patient should report any serious health problems and concerns during a medical and family history, especially those listed below.

Previous episodes of back pain
Any injuries or accidents involving the neck, back, or hips
History of cancer
Unexplained weight loss or chronic infection
The frequency, duration, and nature of the back pain
When the back pain occurs
What triggered the pain (such as lifting a heavy object)
Conditions that make the pain worse such as coughing
Any situation that relieves the pain
Urination of bowel movement problems
Other relevant symptoms such as morning stiffness, weakness, or numbness in the legs.

The main goal of a physician exam is to try and determine the source of the pain and to determine limits of movement.

Patients are asked to sit, stand, and walk in different ways (flat-footed, on the toes, and on their heels).
In some cases they are asked to walk on a treadmill to test for weakness in toe or heel walking (which may indicate stenosis).
Patients will be requested to bend forward, backward, and sideways and to twist.
Patients will be asked to lift their leg straight up while lying down. The doctor will also move the patient's legs in different positions and bend and straighten the knees. (Pain caused by sciatica can be intensified by lifting the affected leg straight in the air. It is usually sharp, localized, and accompanied by numbness or tingling. Pain caused by inflammation is duller and more generalized and not affected by lifting a straight leg.)
The doctor may measure the circumference of the calves and thighs to look for muscle deterioration.
To test nerve function and reflexes, doctors will tap the knees and ankles with a rubber hammer. The doctor may also touch parts of the body lightly with a pin, cotton swab, or feather to test for numbness and nerve sensitivity.

Because most patients with back pain are on the mend or completely recovered within 6 weeks, imaging techniques such as x-rays or scans are rarely recommended in the first month unless a tumor, fracture, infection, cauda equina syndrome, or progressive neurologic disease is suspected.

Patients who have the following symptoms or experienced certain events may need imaging studies.

Pain that lasts more than a month
Very severe or progressive pain, numbness
Muscle weakness
A previous accident or injury that might have affected the back
A history of cancer
Indications of an underlying disease such as fever or unexplained weight loss
Pain that occurs in patients over 65 years of age

If these conditions exist, usually an x-ray is used first. If results are inconclusive, either computed tomography (CT) or magnetic resonance imaging (MRI) may be performed. (Ultrasound is not useful.)

X-Rays. Although many patients with acute and uncomplicated low back pain believe that plain x-rays of the spinal column are important in a diagnosis, they are not very helpful in most patients except for reducing anxiety. If pain persists after 6 - 8 weeks, then x-rays are usually warranted. In such cases, x-rays may reveal signs of injury, infection, tumors, stenosis, or changes in the vertebrae that may be causing inflammation or compression on the nerve. There are many different types of x-rays for the spine.

A diskography is an x-ray of the disk. This procedure requires injections into disks suspected of being the source of pain and disks nearby. It can be painful and is generally only used for patients who are undergoing back surgery to identify the location of the injured disk.
An x-ray myelogram is an x-ray of the spine that requires a spinal injection of a special dye and the need to lie still for several hours to avoid a very painful headache. It has value only for select patients with pain on moving and standing. It has largely been replaced by CT and MRI scans.

CT stands for computerized tomography. In this procedure, a thin x-ray beam is rotated around the area of the body to be visualized. Using very complicated mathematical processes called algorithms the computer is able to generate a 3-D image of a section through the body. CT scans are very detailed and provide excellent information for the doctor.

Magnetic Resonance Imaging (MRI). Magnetic resonance imaging (MRI) can provide very well-defined images of soft tissue and bone. It is not painful, but some people may feel claustrophobic in scanners that are fully enclosed. MRIs can detect annular tears, or disk fragments, and non-spinal causes of back pain, including infection and cancer. However, MRIs are no more effective than x-rays in identifying arthritis, and they are more expensive. Some medical evidence suggests that relying on MRI images of disk abnormalities to determine treatment has resulted in many unnecessary surgeries. At least 40% of all adults have bulging or protruding vertebral disks, and most have no back pain. The degree of disk abnormalities revealed by MRIs often have very little to do with the severity of the pain or the need for surgery. Disk abnormalities in people who have back pain may simply be a coincidence rather than an indication for treatment.

Click the icon to see an image of a MRI machine.

Advanced imaging techniques should be used only when underlying infection, cancer, or nerve involvement is suspected.

Magnetic Resonance Neurography. This imaging exam looks at the nerves in the pelvic area. Researchers reporting in the Journal of Neurosurgery found that it helped reveal pinched nerves that can cause leg pain. The findings could lead to new ways to diagnose sciatica and piriformis syndrome.

Bone Scintigraphy and SPECT Imaging.In rare cases, doctors may use bone scintigraphy (bone scanning) to determine abnormalities in the bones. The technique may be useful for early detection of spinal fractures, cancer that has spread to the bone, or osteoarthritis. During this exam, a small amount of radioactive material is injected into a vein. It circulates through the body, and is absorbed by the bones. The bones can then be visualized using x-rays or single photon emission computed tomography (SPECT). A study in the February 2006 journal Radiology found that SPECT can help determine which patients would get low back pain relief from spinal injections. Forty-seven patients were randomly divided into two groups: One group received SPECT before they were scheduled for an injection, the other group did not. Those who showed spinal problems on the SPECT images received an injection in the area of the abnormalities. Those who had a normal SPECT, as well as those who did not have the test at all, received injections in the area recommended by their referring physician. After a month, those who had targeted injections using the SPECT images had greater pain relieve than those who did not.

Electrodiagnostic tests that analyze the electric waveforms of nerves and muscles may be useful for detecting nerve abnormalities that may be causing back pain and identifying possible injuries. They are also useful to determine if any abnormal structural findings on an MRI or other imaging test have real significance as a cause of the back pain. It should be noted that any nerve injuries that affect these tests may not be present for 2 - 4 weeks after symptoms begin.

Nerve conduction studies and electromyography are the electrodiagnostic tests most commonly performed.

Nerve Conduction Studies. To perform nerve conduction studies, surface electrodes are attached to the skin. Small electric shocks are then applied to measure the speed of nerve conduction.

Electromyography. To perform electromyography, a fine, sterile, wire electrode is inserted briefly into a muscle and the electrical activity is displayed on a viewing screen. Electromyography can be quite painful, and some experts question, in fact, whether it adds any valuable diagnostic information. They suggest it be limited to unusual cases or when other tests indicate that the condition is aggressive and may increase the risk for rapid, significant injury.

Blood and urine samples may be used to test for infections, arthritis, or other conditions.

Injecting a drug that blocks pain into the nerves in the back helps locate the level in the spine where problems occur.

A procedure called a facet block is also useful in locating areas of specific damage.

Provocative diskometry is a test that uses an injection of saline solution into the suspected disk to reproduce the pain, which is then followed by injection of an anesthetic to dull the pain.

Medications

The most commonly prescribed medications for the treatment of back pain are nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. Evidence suggests that short-term use of NSAIDs brings effective relief in patients with acute back pain. The benefits for chronic back pain are less certain.

There are dozens of NSAIDs. The most common are the following:

Over-the-counter NSAIDs include aspirin, ibuprofen (Advil, Nuprin, Motrin IB, Rufen), naproxen (Aleve), ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), flurbiprofen (Ansaid), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), nabumetone (Relafen), dexibuprofen (Seractil), and indomethacin (Indocin).
Topical NSAIDs delivered in gels, creams, or patches do not appear to provide any long-term benefits in reducing arthritic pain.

Many experts now recommend that patients who take NSAIDs by mouth only do so for a short period of time. A 2004 review published in the British Medical Journal suggested that long-term use of NSAIDs does not actually reduce osteoarthritis pain and may increase patients’ risk of experiencing side effects. High dosages of NSAIDs can cause heart problems such as increased blood pressure, kidney problems, and stomach bleeding.

In April 2005, the FDA asked drug manufacturers of prescription NSAIDs to place an alert on their medicines warning people that the drugs have been linked to an increased risk for cardiovascular events and gastrointestinal bleeding. The FDA also requested manufacturers of OTC NSAIDs to revise their labels to include more specific language concerning potential cardiovascular and gastrointestinal risks. Aspirin does not contain such warning labels.

Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the second most common cause of ulcers and the rate of NSAID-caused ulcers is increasing. Ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) are also more likely to bleed than those caused by the bacterium H. pylori.

Doctors cannot predict which patients taking these drugs will develop bleeding.

Among the groups at high risk for bleeding are elderly people, anyone with a history of ulcers of GI bleeding, patients with serious heart conditions, alcohol abusers, and those on certain medications, such anticoagulants ("blood thinners"), corticosteroids, or bisphosphonates (drugs used for osteoporosis).

Proton-pump inhibitors may help to prevent and heal ulcers caused by NSAIDs. Proton-pump inhibitors include omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid).

An ulcer is a crater-like lesion on the skin or mucous membrane that is caused by an inflammatory, infectious, or cancerous condition. To avoid irritating an ulcer, stop smoking and try to eliminate certain substances from your diet, including caffeine and alcohol. Prescription medicines are available to suppress the acid in the stomach that causes erosion of the stomach lining. Endoscopic therapy can be used to stop ulcer-related bleeding.

Coxibs block an inflammation-promoting enzyme called COX-2. This drug class was initially thought to work as well as NSAIDs, while causing less gastrointestinal distress. However, following numerous reports of cardiovascular events, gastrointestinal problems, and skin rashes, the FDA is currently re-evaluating the relative risks and benefits of this drug class. Rofecoxib (Vioxx) and valdecoxib (Bextra) have been withdrawn from the United States market. Celecoxib (Celebrex) is still available, but patients should ask their doctor if this drug is appropriate and safe for them.

Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties, but is not as addictive. (Dependence and abuse have been reported, however.) It can cause nausea, but does not cause the severe gastrointestinal problems that NSAIDs can. Some patients who take tramadol experience severe itching. A combination of tramadol and acetaminophen (Ultracet) is now available. It provides more rapid pain relief than tramadol alone.

Narcotics are pain-relieving and sleep-inducing drugs that act on the central nervous system. They are the most powerful medications available for the management of pain.

There are two types of narcotics:

Opiates are derived from natural opium such as morphine and codeine.
Opioids are synthetic drugs and include oxycodone (Percodan, Percocet, Oxycontin), hydrocodone (Vicodin), and oxymorphone (Numorphan).

Novel ways to deliver pain medicine have been developed. A skin patch containing an opioid called transdermal fentanyl (Duragesic) may relieve chronic back pain more effectively than oral opioids. For very severe pain, a small, patient-controlled pump called SynchroMed may be used. This device is implanted under the skin in the abdomen and delivers pulses of pain-relieving opioids to the spinal canal.

Common side effects of opioids include anxiety, constipation, nausea and vomiting, dizziness, drowsiness, paranoia, urinary retention, restlessness, and labored or slow breathing. Addiction is a risk, although less than is commonly believed when these medications are used for pain relief. In fact, when prescribed properly, use of opioids for chronic pain can be safer in some cases than on-going use of NSAIDs. Unfortunately, opioid abuse among young people is a major concern. Unless the pain is very severe, experts advise against routinely prescribing opioids.

Injections of different substances are sometimes used to treat low back pain caused by nerve impingement. The injection is usually an epidural, which is directed into the spaces between the outer membrane of the spine and the vertebrae. None of these substances cure the problem.

Corticosteroids. An injection of a corticosteroid (commonly called a steroid) is directed as close to the injured location as possible. Corticosteroids reduce inflammation. This approach may temporarily relieve sciatic pain until the body heals itself. Studies that measure the benefits of steroids on sciatica or low back pain are conflicting. There is some evidence that patients can experience rebound pain within a few months. Some experts have also raised concerns that even a single injection can cause serious and painful side effects, including meningitis and inflammation, although such risks are very low.
Hypertonic saline (salt water solution). Epidural injections of saline are being investigated for breaking up scar tissue. One 2001 study compared targeted injections of saline and steroids directed at the nerve root. Although steroid injections had more immediate benefits, both products offered improvement. By the third month, patients who had saline injections experienced less pain than the steroid group. A 2003 study found that epidural corticosteroid injections provided no greater benefit than saline injections for patients with sciatica.
Local anesthetics. Injections of anesthetics such as Xylocaine or bupivacaine may help some patients, although studies on their benefits are mixed.
Botulinum. Researchers are investigating whether injections of botulinum toxin (Botox) in the lower back can safely and effectively relieve pain. Very small amounts of Botox temporarily paralyzes muscle tissue. Botox is commonly used to smooth out wrinkles. Some studies have suggested that Botox may be very helpful in relieving chronic low back pain and sciatica caused by piriformis syndrome. In a 2001 study, the benefits of Botox injections for low back pain subsided within 6 months.

A 2002 review of studies concluded that antidepressants may lessen pain severity in some patients, although they had little effect on daily functioning. Antidepressants called tricyclics can be effective painkillers in non-depressed people with chronic back pain. Such antidepressants include amitriptyline (Elavil, Endep), desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), amoxapine (Asendin), nortriptyline (Pamelor, Aventyl), and maprotiline (Ludiomil). It should be noted that tricyclics can have severe side effects. Nonetheless, experts believe there is a useful role for these drugs that warrants further investigation.

A combination of nonsteroidal anti-inflammatory drugs (NSAIDs) and muscle relaxants such as cyclobenzaprine (Flexeril), diazepam (Valium), carisoprodol (Soma), or methocarbamol (Robaxin) are sometimes used for patients with acute low back pain. Medical evidence has found that they can help relieve non-specific low back pain, but some experts have warned that these drugs should be used cautiously, since they target the brain, not the muscles. Patients who take muscle relaxants may experience a number of central nervous system side effects such as drowsiness. The muscle relaxant Soma can be addictive and does little more than produce sleep.

Tumor-Necrosis Factor (TNF) Modifiers. TNF modifiers block the action of tumor necrosis factor, a protein involved in inflammatory response. Because of their anti-inflammatory properties, TNF modifier drugs are being investigated for the treatment of the nerve dysfunction and pain that occurs in sciatica. Some small studies indicate that infliximab (Remicade) may help reduce sciatica pain. Early studies suggest that another TNF modifier, etanercept (Enbrel), may be useful for treating sciatica and back pain. TNF modifiers are powerful drugs that can cause severe side effects.

Lidocaine Patch. A skin patch containing lidocaine, a local anesthetic, has been used specifically for herpes zoster pain. Early studies suggest that this patch, called Lidoderm, may provide significant relief for people who suffer from low back pain with very few adverse effects, even with continuous use of four patches a day. If further studies support its benefits, the patch could prove to be an important treatment

NO-NSAIDs. NO-NSAIDs are drugs that combine NSAIDs and nitric oxide (NO), a substance that enhances blood flow to the stomach and increases levels of protective mucus and bicarbonate. These agents show particular promise in providing pain relief and reducing the risk for GI problems.

Most herbal remedies used for back pain have both pain-relief and anti-inflammatory effects. Popular herbs for back pain relief include:

White willow bark (Salix alba) contains salicylates, the same chemicals found in aspirin.
Bromelain is an enzyme found in pineapple.
Boswellia (Boswellia serrata) is an herb commonly used in Indian Ayurvedic medicine.
Devil’s claw (Harpagophytum procumbens) is an African herb sometimes used to relieve arthritic pain.

White willow bark, bromelain, and Boswellia have blood-thinning properties and can interfere with anticoagulant medications such as warfarin (Coumadin).

Complementary and Alternative Medicine

A number of complementary and alternative treatments are used to relieve back pain. Complementary means it is used together with conventional medicine. Alternative means it is done in place of conventional medicine.

Acupuncture is now a common alternative treatment for certain kinds of pain. It involves inserting small needles or exerting pressure on certain "energy" points in the body. When the pins have been placed successfully, the patient is supposed to experience a sensation that brings a feeling of fullness, numbness, tingling, and warmth with some soreness around the acupuncture point. Unfortunately, rigorous studies of acupuncture are difficult to perform, and most evidence on its benefits is weak. In any case, it may be specifically helpful for certain patients with back pain, such as pregnant women, who must avoid medications. Anyone who undergoes acupuncture should be sure it is performed in a reputable location by experienced practitioners who use sterilized equipment.

Click the icon to see an image of acupuncture.

A number of well-conducted studies have supported the benefits of massage therapy for patients with chronic or acute back pain, especially when it is combined with exercise and patient education. In fact, one analysis in 2003 suggested it may reduce the costs of care. However, it is usually not covered by insurance.

According to a 2001 review of studies, only intensive programs that include both psychological and physical rehabilitation therapies were successful in reducing chronic low back pain and improving function. A number of effective approaches to low back pain -- collectively called mind-body techniques -- employ psychological, behavioral, or physical methods to promote relaxation and reduce stress. Although many may be helpful, evidence is lacking on the specific approaches that would be most successful and which patients would most likely benefit.

Stress Reduction. Stress reducing techniques, including relaxation methods and meditation, may be helpful. One study, for example, reported that meditation was beneficial in reducing pain and improving mood among chronic pain sufferers who had not responded to traditional care. Another found that after 3 weeks, patients who were in pain after back surgery had less discomfort and slept better after practicing relaxation imagery techniques while listening to music for 25 minutes a day.

Cognitive-Behavioral Therapy. Studies report that a course of cognitive-behavioral therapy helps reduce chronic back pain or at least enhances the patient's ability to deal with it. The primary goal of this form of therapy in such cases is to change the distorted perceptions that patients have of themselves and their approach to pain. Using specific tasks and self-observation, patients gradually shift their fixed ideas that they are helpless against the pain that dominates their lives to the perception that pain is only one negative and, to a degree, a manageable experience among many positive ones. In one study, therapists also taught relaxation techniques and methods to improve posture. The sessions lasted for 2.5 hours each week for 12 weeks. More research is needed.

Patient Education and Support Groups. A 2002 study reported that patients with chronic low back pain who participated in an expert-moderated e-mail support and discussion group had less pain and disability after 12 months. An Australian massive public-health campaign that educated patients and doctors about the importance of staying active and dispelled fears about long-term impairment from back pain dramatically reduced disability and worker compensation claims.

Spinal Manipulation for Uncomplicated Acute Low Back Pain. Spinal manipulation may be useful for acute back pain that persists beyond 2 - 3 weeks. There are a number of variations, but one example of a spinal manipulation technique is the following:

The patient first lies on their side.
The practitioner grasps the exposed shoulder and either the hip or knee and then presses the upper and lower portions of the body in opposite directions, so that the torso rotates.
The shifting vertebrae make a cracking or popping sound, indicating that they have exceeded the normal range of motion.
Often this results in a greater sense of ease and mobility. (The effect, however, may be temporary.)

Whether on-going manipulations relieve pain better that just one visit is a subject of debate. Some patients consider spinal manipulation to be highly effective for chronic low back pain. A major 2003 analysis, however, reported that current evidence did not support the benefits of spinal manipulation over general medical care or physical therapy for either acute or chronic back pain. [It was better than sham (fake) therapy, however.]

Spinal manipulations are typically performed by chiropractors, but osteopathic doctors also perform them.

One in three people with low back pain seek treatment from a chiropractor. Chiropractic was founded in the U.S. in the late 1800s. The specific goal of chiropractors is to perform spinal manipulations to improve nerve transmission. Many studies have now confirmed that patients feel more satisfied with their chiropractic care than with treatment from general practitioners.
Osteopathy was also founded in the 1800s. Its core approach to healing also involves physical manipulation. Osteopathy manipulates the bones, muscles, and tendons to optimize blood circulation. The general direction of osteopathy over the years has widened to employ a broader range of treatments that now approach those of standard medicine. One 1999 study reported that osteopathy was as effective as medical treatment in relieving low back pain and patients required far less medication and physical therapy. Osteopathic treatment was also far less expensive than traditional back pain treatments.

Both chiropractors and osteopaths offer verbal assurance and a precise treatment regimen. The direct physical connection through spinal manipulation reinforces the patient-practitioner relationship. The emotional effects of such connections may be as important for healing as the treatments themselves.

Mild and temporary side effects from spinal manipulation are common. The potential for serious adverse effects from low back manipulations is low. It should be strongly noted, however, that serious complications (including stroke or spinal cord or neck injury) have been reported with manipulations of the neck. Although little research has been done on such complications, an English survey indicated that they are more frequent than commonly thought.

Some chiropractors may take a lot of x-rays, particularly those of the full spine, which may have long-term harmful consequences. Patients should also be aware that some chiropractors use alternative treatments that have not been proven or rigorously studied. All patients should require objective evidence on the benefits of their treatments.

Vertebral Axial Decompression. Vertebral axial decompression (VAX-D) may reduce pain and improve function in patients with chronic low back pain, including sciatic pain that radiates down the leg. The patient lies face down on a special table, clutching hand grips and wearing a pelvic harness. The traction-like action alternately decompresses and relaxes the spine over 1-minute intervals. Each session lasts about 30 minutes. Ten to 20 sessions on successive days are often required. The procedure is thought to alleviate pain and enhance healing by relieving pressure within the disks, promoting the in-flow of oxygen, fluids, and nutrients to the spinal column. Some evidence supports its benefits, with reported success rates of around 70%. Because it is considered experimental, it is not yet covered by most insurers. More studies are needed to confirm its possible benefits.

Percutaneous Neuromodulation Therapy. A technique called percutaneous neuromodulation therapy (PNT) uses a small device delivers electrical stimulation to deep tissues and nerve pathways near the spine. It has shown some initial promise for relief of chronic back pain and may also improve mobility and sleep. Treatment sessions are conducted in the doctor's office and last about 30 minutes. A correct pattern of stimulation appears to be important for optimal relief and needs to be determined.

Electric Nerve Stimulation. Transcutaneous electric nerve stimulation (TENS) uses low-level electrical pulses to suppress back pain. A variant, percutaneous electrical nerve stimulation (PENS), applies these pulses through a small needle to acupuncture points. The standard procedure is to give 80 - 100 pulses per second for 45 minutes three times a day. The patients are barely aware of the sensation. Although a 2002 analysis of trials could find no direct evidence of benefit, small studies have reported some relief for chronic low back pain from either TENS or PENS. It is not known if these effects are long lasting. Neither approach is helpful for relief of acute low back pain in most patients.

Muscle Stimulation. Two investigative procedures called automated or electrical twitch obtaining intramuscular stimulation (ATOIMS or ETOIMS) are showing promise. ATOIMS uses an automated mechanical device that vibrates the muscle using a tiny pin. (The sensation is described as similar to a mosquito bite.) ETOIMS uses an extremely mild electrical current. They can also be used together. Both approaches cause the muscles to twitch and then relax then the process is stopped. Discomfort is minimal. Small studies are reporting some help in relieving a number of condition the cause chronic pain, including low back pain.

Therapeutic ultrasound. Therapeutic ultrasound involves placing a small wand or probe directly onto the skin. The wand gives off sound waves, which gently vibration the area. Scientists in England are studying whether therapeutic ultrasound may help relieve pain and disability due to sciatica.

Intradiscal Electrothermal Treatment (IDET). Intradiscal electrothermal treatment (IDET) uses electricity to heat a painful disk. Heat is applied for about 15 minutes. Pain may temporarily feel worse, but after healing, the disk shrinks and becomes desensitized to pain. However, healing takes several weeks. The surgery may not work in obese patients.

Some studies have reported positive benefits to IDET; others say it does not significantly reduce pain. A randomized, blinded study published in the November 2005 journal Spine found that IDET was no better than a sham (fake) procedure in relieving chronic back pain due to disk disease. For the study, patients were randomly selected to receive either IDET or a sham procedure. After 6 months, there was no difference in pain symptoms between the two groups.

Exercise and Physical Therapy

Incorrect movements or long-term high-impact exercise is often a cause of back pain in the first place. People vulnerable to back pain should avoid activities that put undue stress on the lower back or require sudden twisting movements, such as football, golf, ballet, and weight lifting.

Exercise does not help acute back pain. In fact, overexertion may cause further harm.

An incremental aerobic exercise program (such as walking, stationary biking, swimming) may begin within 2 weeks of symptoms. Jogging is usually not recommended, at least not until the pain is gone and muscles are stronger.

Patients should avoid exercises that put the lower back under pressure until the back muscles are well toned. Such exercises include leg lifts done in a facedown position, straight leg sit-ups, and leg curls using exercise equipment.

In all cases, patients should never force themselves to exercise if, by doing so, the pain increases.

Exercise plays a very beneficial role in chronic back pain. Repetition is the key to increasing flexibility, building endurance, and strengthening the specific muscles needed to support and neutralize the spine. Exercise should be considered as part of a broader program to return to normal home, work, and social activities. In this way, the positive benefits of exercise not only affect strength and flexibility but they also alter and improve patients' attitudes toward their disability and pain. Exercise may also be effective when combined with a psychological and motivational program, such as cognitive-behavioral therapy.

There are different types of back pain exercises. A 2005 review in the Annals of Internal Medicine found that stretching exercises worked best for reducing pain, while strengthening exercises were best for improving function.

Back pain exercises include:

Low Impact Aerobic Exercises. Low-impact aerobic exercises, such as swimming, bicycling, and walking, can strengthen muscles in the abdomen and back without over-straining the back. Programs that use strengthening exercises while swimming may be a particularly beneficial approach for many patients with back pain. Medical research has shown that pregnant women who engaged in a water gymnastics program have less back pain and are able to continue working longer.
Lumbar Extension Strength Training. Exercises called lumbar extension strength training are proving to be effective. Generally, these exercises attempt to strengthen the abdomen, improve lower back mobility, strength, and endurance, and enhance flexibility in the hip and hamstring muscles and tendons at the back of the thigh.
Yoga, Tai Chi, Chi Kung. Practices originating in Asia that combine low-impact physical movements and meditation may be very helpful. They are designed to achieve a physical and mental balance and can be very helpful in preventing recurrences of low back pain.
Pilates, an exercise practice that uses yoga principles, may be specifically helpful.
Flexibility Exercises. Flexibility exercises may help reduce pain. A stretching program may work best when combined with strengthening exercises.
Retraining Deep Muscles. Some studies suggest a link between low back pain and impaired motor control of deep muscles of the back and trunk. According to these studies, contraction exercises specifically designed to retrain these muscles may be effective for patients with both acute and chronic pain.

Perform the following exercises at least three times a week:

Partial Sit-ups. Partial sit-ups or crunches strengthen the abdominal muscles.

Keep the knees bent and the lower back flat on the floor while raising the shoulders up 3- 6 inches.
Exhale on the way up and inhale on the way down.
Perform this exercise slowly 8 - 10 times with the arms across the chest.

Pelvic Tilt. The pelvic tilt alleviates tight or fatigued lower back muscles.

Lie on the back with the knees bent and feet flat on the floor.
Tighten the buttocks and abdomen so that they tip up slightly.
Press the lower back to the floor, hold for one second, and then relax.
Be sure to breathe evenly.

Over time increase this exercise until it is held for 5 seconds. Then, extend the legs a little more so that the feet are further away from the body and try it again.

Stretching Lower-Back Muscles. The following are three exercises for stretching the lower back:

Lie on the back with knees bent and legs together. Keeping arms at the sides, slowly roll the knees over to one side until totally relaxed. Hold this position for about 20 seconds (while breathing evenly) and then repeat on the other side.
Lying on the back, hold one knee and pull it gently toward the chest. Hold for 20 seconds. Repeat with the other knee.
While supported on hands and knees, lift and straighten right hand and left leg at the same time. Hold for 3 seconds while tightening the abdominal muscles. The back should be straight. Alternate with the other arm and leg and repeat on each side 8 - 20 times.

Note: No one with low back pain should perform exercises that require bending over right after getting up in the morning. At that time, the disks are more fluid-filled and more vulnerable to pressure from this movement.

Physical therapy with a trained professional may be useful if pain has not improved within the first 3 weeks. It is, in fact, important for any person who has chronic low back pain to have an exercise program guided by professionals who understand the limitations and special needs of back pain and who can address individual health conditions. One study indicated that patients who planned their own exercise did worse than those in physical therapy or doctor-directed programs.

Physical therapy typically includes the following:

The first stage involves patient education and training the patient in correct movement. Sometimes heat or electro-therapies (such as therapeutic ultrasound or low-energy lasers) are used, although their benefits are unproven.
If back pain persists beyond 5 weeks, physical therapy is used for rehabilitation. It uses exercises to help the patient keep the spine in neutral positions during all daily activities.

Surgery

Diskectomy is the surgical removal of the diseased disk. The procedure relieves pressure on the spine. It has been performed for 40 years with increasingly less invasive techniques being developed over time. However, few studies have been conducted to determine its real effectiveness. In appropriate candidates it provides faster immediate relief than medical treatment, but long-term benefits (over 5 years) are uncertain. A number of minimally invasive variations are now available.

When the soft, gelatinous central portion of an intervertebral disk is forced through a weakened part of a disk, it is called a slipped disk. Most slipped disks (herniated disks) take place in the lumbar area of the spine. Slipped disks are one of the most common causes of lower back pain. The mainstay of treatment is an initial period of rest with pain and anti-inflammatory medications followed by physical therapy. If pain and symptoms persist, surgery to remove the herniated portion of the intervertebral disk may be needed.

Microdiskectomy. Microdiskectomy is the current standard procedure. It is performed through a small incision (1 to 1-1/2 inch). The back muscles are lifted and moved away from the spine. After identifying and moving the nerve root, the surgeon removes the injured disk tissue under it. The procedure does not change any of the structural supports of the spine, including joints, ligaments, and muscles.

Other less invasive procedures that are available including the following:

Endoscopic Diskectomy. Endoscopy employs a catheter (a thin tube) that contains tiny cameras and surgical instruments that are inserted through small incisions. Various endoscopic approaches are proving to be useful for back surgery.
Percutaneous Diskectomy. Percutaneous diskectomy (PAD). This approach uses a tube with a device at the tip that cuts away some of the nucleus pulposus and a vacuum that then sucks this gelatinous matter out.
Laser Diskectomy. A number of investigative surgical procedures employ lasers. For example, endoscopic laser foraminoplasty (ELF) uses lasers to locate the likely source of pain and remove diseased tissue. The incision requires little more than a Band-Aid and complications are minimal. Long-term benefits are unknown, however.

It is not clear yet if any of these less-invasive procedures are any more effective than the standard microdiskectomy.

Complications and Outlook. Many patients still have back pain after diskectomy that delays discharge from the hospital. Narcotics are usually needed. Adding an injected NSAID may speed resolution of pain.

Scar tissue is a significant problem, since it can cause persistent low back pain afterward. Anti-scarring agents or certain devices may help reduce surgical scars and thereby postoperative pain. Other complications of spinal surgery can include nerve and muscle damage, infection, and the need for reoperation.

Patients now often remain in bed only 3 - 4 days after disk surgery. It may take 4 - 6 weeks for full recovery, however. Gentle exercise may be recommended at first. Starting intensive exercise 4 - 6 weeks after a first-time disk surgery appears to be very helpful for speeding up recovery.

Operations that remove a vertebra (laminectomy) or shave off part of one (laminotomy) may be used in certain cases of spinal stenosis or spondylolisthesis to decompress the nerve. They may also be used to remove benign tumors on the spine.

Click the icon to see an illustrated series detailing lumbar spinal surgery.

Although either procedure often brings immediate relief from pain, a 1999 statistical study suggested that it is inappropriately performed in 60% or more of sciatica cases. There are small risks to the operation, and it is not always successful. Some recurrence of back pain and sciatica occurs in half to two-thirds of postoperative patients. Minimally invasive variations are under investigation.

In cases where abnormal vertebrae position or movement is responsible for severe and chronic back pain, such as spinal stenosis or spondylolisthesis, surgeons may fuse vertebrae together. Fusion uses a bone graft or some other device to join the vertebrae together. In a 2001 study of patients with severe long-term back pain, 33% of patients who had spinal fusion had less back pain after 2 years, compared to 7% who received conservative treatment with physical therapy. Pain improved most in the 6 months following surgery. However, a 2005 clinical trial found that spinal fusion surgery worked no better than intensive rehabilitation in reducing disability. The intensive rehabilitation program included both physical and cognitive-behavioral therapy.

Many spinal fusion surgeries use a tiny hollow metal cage, which is implanted into the disk space. Bone is then removed from the patient's hip and packed inside the cage. Over time the bone grows through the holes and around the device, fusing the vertebrae. Alternatively, rather than performing a bone graft, the cage is filled with a sponge-like material containing a genetically-engineered protein called InFuse (rhBMP-2) that promotes bone to grow.

Click the icon to see an illustrated series detailing spinal fusion.

A number of video-assisted techniques have been developed. The new techniques are less invasive than standard "open" surgical approaches, which uses wide incisions. To date, however, the newer procedures have higher complication rates than the open approaches and some medical centers have abandoned them.

Percutaneous Vertebroplasty. Percutaneous vertebroplasty involves the injection of a cement-like bone substitute into vertebrae with compression fractures. It is done under endoscopic and x-ray guidance. The technique is proving useful for stabilizing the spine and relieving pain in patients with spinal compression fractures due to osteoporosis or cancer. A Mayo Clinic study found that patients who have the procedure have less back pain during rest and activity. A survey of records from more than 100 vertebroplasty patients revealed that most patients are more functional than before the procedure, and the benefits lasted for up to a year. Warning: The FDA has warned consumers that polymethylmethacrylate bone cement, used during vertebroplasty, could leak. Such leakage could cause damage to soft tissues and nerves. It is extremely important that the patient is sure that the health care provider has had significant experience performing the vertebroplasty procedure.

Percutaneous kyphoplasty. The health care provider injects bone cement into the space surrounding a fractured vertebra. (Vertebroplasty injects the cement directly into the vertebra.) Kyphoplasty is used to stabilize the spine and return spinal cord height to as normal as possible. However, a review published in 2006 by a nonprofit health services research agency found that the technique does not improve a person's back pain or quality of life. Kyphoplasty should only be done if bed rest, medicines, and physical therapy do not relieve back pain. Those with severe fractures or spinal infections should not have kyphoplasty.

Artificial Disk Replacement. Total disk replacement is an investigative procedure for some patients with severely damaged disks. The technique implants artificial disks (ProDisc, Link, SB Charite) consisting of two metal plates and a soft core. The surgery can be performed using a minimally invasive laparoscopic procedure, which is performed through tiny cuts using miniature tools and viewing devices. A study in 2003 was the first to suggest that it may eventually achieve results that are comparable to standard surgeries for disk herniation. An artificial cushioning device called the prosthetic disk nucleus (PDN) replaces only the inner gel-like core (nucleus pulposus) within the intervertebral space, rather than the entire disk. It is showing promise in early studies.

Nerve Blocks. A number of surgical techniques are available for relieving pain by impairing nerves that are causing pain due to impingement. Medical research has shown that 60% of the patients who received electrical stimulation to block the nerves reported at least 90% relief of pain after a year; 87% reported at least 60% relief.

Other Treatments

Radiofrequency Nerve Destruction. Radiofrequencies are being used to destroy nerves involved in the facet joints (or z-joints), which connect the vertebrae. Evidence is still weak on its benefits. A 2003 analysis suggested that it may be beneficial, however, for relief of neck pain and possibly for low back pain caused by problems in the facets joints. Serious infections have been reported.

Stem cell treatments. Researchers in England have pioneered a new technique to grow new spinal tissue using the patient's own stem cells. Stem cells are the building blocks of specific cells. Every cell in the human body starts (or "stems") from a stem cell. The new tissue will replace damaged spinal tissue and may relieve low back pain. Researchers expect the treatment to enter pre-clinical trials in about 1 year.

Specific Treatment for Acute Low Back Pain

Patients with short-term acute low back pain usually have the best results with the least aggressive treatments. The general approach is as follows:

Patients with no serious underlying cause should stay as active as possible within the limits of the back pain. (Bed rest is not recommended.)
Physical therapy or spinal manipulations may be helpful if pain continues for more than 2 - 3 weeks.
The patient should seek a specialist if pain continues for more than 1 month. (Some patients may need to see a specialist sooner if there is an underlying disorder, nerve damage, or injury.) Back pain due to medical conditions such as arthritis, osteoporosis, or pregnancy either goes away when the underlying condition disappears or is treated.

Home Care Tips for Relieving Pain

Resume normal activity as soon as possible. Bed rest is no longer recommended and may delay recovery. Activities should be done without strain or stretching.
Avoid intense exercise and physical activity, particularly heavy lifting and trunk twisting if there is acute back pain.
Try an over-the-counter nonsteroidal anti-inflammatory such as aspirin or ibuprofen. These medicines often provide significant benefits.
Apply heat (104°) to the painful area. Heat may work better than ibuprofen or acetaminophen. One group of researchers found that people with low back pain who wear low-level heat wraps for 8 hours a day have significant less pain and disability.
Try alternating between hot and cold packs. Some doctors recommend changing from hot to cold every 3 minutes and repeating this sequence three times. Others believe ice packs should be applied first. This routine should be done two or three times during the day. (Note: Heat or cold treatments do not have much effect on sciatica.)
Supportive back belts, braces, or corsets may help some people temporarily, but these products can reduce muscle tone over time and should be used only briefly.
Get plenty of sleep. Healthy sleep plays a vital role in recovery. Avoid caffeine in the afternoon and evening, and unwind before bed by taking a warm bath or practicing relaxation techniques. It is often difficult to get a good night's sleep when suffering from back pain, particularly because the pain can intensify at night. Some people may need medicine to help manage nighttime pain or treat sleeplessness. Lying curled up in a fetal position with a pillow between the knees or lying on the back with a pillow under the knees may help.

Prescription muscle relaxants may help some patients, although their benefits are uncertain. Once started, medications should be taken on a regular schedule in order to maintain consistent effectiveness.

Massage therapy may help relieve both acute and chronic low back pain. Several well-conducted studies have shown some benefit and suggest it may reduce the costs of care. Massage therapy may not be covered by health insurance.

Spinal manipulation may help, although it is not clear if it works any better than physical therapy or general care. Some experts recommend delaying this treatment until pain has persisted for 3 weeks, if possible, since the back pain will most likely have gone away on its own by then.

Acupuncture has not proven to have any value for acute low back pain in most patients, but may provide some help for patients with chronic low back pain.

Be aware of and avoid approaches that are not helpful. Certain approaches may even be harmful for acute low back pain. For example, permanent bipolar magnets (magnet therapies) can deactivate heart devices and must be kept at least six inches away from pacemakers or implantable cardioverter defibrillators. These magnets have gained some popularity as a non-invasive method of relieving pain, but no studies support the claims.

Specific Treatment for Chronic Low Back Pain

Evidence strongly suggests that only intensive treatment, involving both physical and psychological rehabilitation programs, can reduce pain and improve function in patients with chronic low back pain. Even with the best treatments, many patients with chronic back pain fail to have complete pain relief. They often must develop methods for coping with persistent pain.

Early treatments for severe or chronic low back pain are similar to those of acute uncomplicated low back pain.

Pain relievers, particularly non-steroidal anti-inflammatory drugs (NSAIDs), may help relieve symptoms, although they can have severe effects on the gastrointestinal tract over time. Some doctors have recommended long-term opioids for patients with severe chronic pain, but studies suggest they do not improve activity levels and can have significant side effects.

Corticosteroid injections and tricyclic antidepressants may be helpful for some patients.

Specific and regular exercise under the guidance of a trained professional is important for reducing pain and improving function, although patients often find it difficult to maintain therapy.

A new type of physical therapy, called Souchard's global postural re-education, helps relieve back pain symptoms due to degenerative disk disease, according to research presented at the 2005 American Academy of Neurology Annual Meeting. The method involves stretching weakened muscles around the spine and stomach. Researchers studied 102 people who had at least 7 months of severe back pain due to disk disease and who had received different types of treatment for more than 6 months. They attended the new physical therapy sessions two times the first week, then once a week for an average of 5 months. Ninety-two percent had significant pain relief and returned to their normal daily activities. The majority of those who had pain relief felt better after 3 weeks, and remained pain free for almost 2 years.

Alternative therapies may help. Transcutaneous electrical nerve stimulation (TENS) and massage may relieve pain. Mind-body techniques such as relaxation and meditation may be help reducing stress-related pain. Cognitive-behavioral therapy helps change behavior and attitudes toward pain.

Acupuncture may provide longer-lasting pain relief than physical therapy, according to a study in the British Medical Journal. For the study, 129 people were given either 6 acupuncture or physical therapy sessions. The study authors cautioned that the benefit of acupuncture greatly depended on the health care provider’s experience. Another study, published in the Archives of Internal Medicine, reported that acupuncture worked better than no treatment at all.

Yoga relieves low back pain better than conventional exercise or self-help books, according to a study published in the December 20, 2005, issue of Annals of Internal Medicine. For the study, 101 adults with low back pain who were randomly assigned to one of three groups. One group attended yoga classes and lessons; the second did aerobics, weight training, and stretching; and third group read a self-help book about back pain. After 12 weeks, those who took yoga could better perform daily activities requiring the back than those in the other two groups. After 26 weeks, those who took yoga had less pain and better back function, and used fewer pain relievers than the others.

Patients should always try all possible non-surgical treatments before opting for surgery. The most common reasons for surgery for low back pain are sciatica and spinal stenosis. Some experts believe that less than 1% of back pain patients need aggressive medical or surgical treatments.

Nevertheless, when it is appropriate, surgery can provide great relief. Many approaches and procedures are available or being investigated. However, there have been few well-conducted studies to determine if any type of back pain surgery works better than others, or if a single procedure is better than no surgery at all.

People who are obese and have low back pain may benefit from surgical weight loss surgery. A study in the journal Obesity Surgery found that bariatric (stomach stapling) surgery significantly improves the degree of disability in morbidly obese patients who have low back pain.

Before having any surgery, it is extremely important that the patient is sure that the surgeon has had significant experience with the procedure.

Nonsurgical Procedures. Patients with herniated disks should try nonsurgical treatments for at least 1 month before considering surgery. Nonsurgical procedures include spinal manipulation, massage therapy, and physical therapy. Patients should wait at least 2 - 3 weeks before using spinal manipulation.

Surgery. According to a 2001 review of studies, about 10% of patients have such bad back pain after 6 weeks that a diskectomy may be considered. Diskectomy is the standard procedure for herniated disks. For many of these patients, surgery may bring significant relief. In one study, 70% of patients with moderate-to-severe sciatica who had had surgery reported improvement. In most patients, the improvement was better than that achieved by 4 years of nonsurgical treatments. It is not clear if surgery maintains its advantage for longer periods of time.

Preventing Falls. Falling is a risk for patients with spinal stenosis. They should avoid alcohol and sedatives. Leg strengthening exercises such as walking and cycling may be helpful.

Nonsurgical Treatments. The use of common pain relievers such as NSAIDs, physical therapy, and spinal injections may be helpful for some patients.

Surgery. If pain is persistent, patients may require surgery, most often a procedure called decompressive laminectomy. Some patients may require spinal fusion as well. Studies suggest that surgery reduces back pain in many patients with spinal stenosis, at least for a few years. However, by 4 years after surgery, 30% of patients have severe pain again, and 10% have another operation. It should be noted that surgery does not always improve outcome and, in some cases, can even make it worse. Surgery can be an extremely effective approach, however, for certain patients whose severe back pain does not respond to conservative measures.

The general approach for patients with piriformis syndrome is corticosteroid injections and physical therapy. Botox injections are showing promise.

In carefully selected patients who do not respond to physical therapy and injections, some studies report dramatic pain relief with a surgical procedure that releases the piriformis muscle.

Prognosis

Most people with acute low back pain are back at work within a month and fully recover within a few months. According to one study, about a third of patients with uncomplicated low back pain significantly improved after a week; two-thirds recovered by 7 weeks.

However, studies now suggest that up to 75% of patients suffer at least one recurrence of back pain over the course of a year. In another study, after 4 years, less than half were symptom-free. Some doctors are approaching the problem as one that is not necessarily curable and which needs a consistent on-going approach.

Specific conditions can determine the rate of improvement:

In the majority of patients with herniated disks, the condition improves (although the actual physical improvement may be slower than the reduction in pain). Researchers attempted to identify factors most likely to predict an elevated risk for recurrent pain and found that only depression was a significant factor in the majority of those who had not recovered.
Spinal stenosis stabilizes in about 70% of cases and worsens in 15%.

Studies have found that when people stay home because of back injury, only 65% are back at work within a week. Nearly 14% are still absent at one month. If someone is on disability for more than 6 months, the chance of them returning to work is only 50%.

Low back pain accounts for significant losses in work days and dollars. In 1990, it cost the U.S. $23 billion in direct medical costs and possibly as much as $85 billion in total costs (such as lost productivity). Chronic back pain has become one of the most expensive causes of disability among workers under the age of 45. One study found that, although severe back pain comprised only 10% of workers compensation cases, it accounted for 86% of compensation costs.

Complications

Certain warning signs should alert a patient to see a doctor immediately for low back pain. Any very severe back pain warrants attention, particularly if any of the following conditions are present:

Being over 50
Recent injury
Severe pain
Pain awakens the person at night
Pain accompanied by fever (possible infection)
Pain increased by lying down
Pain unrelated to movement
Pain lasts for a month, and is accompanied by unexplained fever or weight loss
History or chronic use of corticosteroids
Intravenous drug use
History of urinary tract infection
In children, any severe neck or back pain or pain that persists for more than 3 days

Cauda equina syndrome is the impingement of the cauda equina (the four strands of nerves leading through the lowest part of the spine). It is an emergency condition that can cause severe complications of the bowel or bladder. Cauda equina syndrome is usually caused by massive extrusion of the disk material. It can cause permanent incontinence if not promptly treated with surgery. Symptoms of the cauda equina syndrome include:

Dull back pain
Weakness or numbness in the buttocks, in the area between the legs, or in the inner thigh, backs of legs, or feet. May cause difficulty in standing or stumbling.
An inability to control urination and defecation
Pain accompanied by fever (can indicate an infection)

Prevention

Exercise, diet, stress, and weight all have a significant influence on back pain. Changing certain lifestyle factors can help reduce and, possibly, prevent backaches.

Smokers are at higher risk for back problems, perhaps because smoking decreases blood circulation. The link may also be due to an unhealthy lifestyle in general. A British study found that young adults who were long-term smokers were nearly twice as likely to develop low back pain as nonsmokers.

Sedentary Lifestyle. People who do not exercise regularly face an increased risk for low back pain, especially when they perform sudden, stressful activities such as shoveling, digging, or moving heavy items. Although no definitive studies have been done to prove the relationship between lack of exercise and low back pain, some doctors believe that an inactive lifestyle may be to blame in some cases. Lack of exercise leads to the following conditions that may threaten the back:

Stiff muscles can make it hard to move, rotate, and bend the back.
Weak stomach muscles can increase the strain on the back and cause an abnormal tilt of the pelvis.
Weak back muscles may increase the risk for disk compression.
Obesity puts more weight on the spine and increase pressure on the vertebrae and disks. However, studies report only a weak association between obesity and low back pain.

Improper or Intense Exercise. Improper or excessive exercise may also increase one's chances for back pain.

Some research suggests that over time, high-impact exercise may increase the risk for degenerative disk disease. A survey of people who played tennis, however, found no increased risk for low back pain or sciatica.
Between 30 - 70% of cyclists experience low back pain. One 1999 study reported that 70% of cyclists reported improvement simply by adjusting the angle of the bicycle seat.
Improper exercise instruction and inattention to body movements can lead to back trouble. For example, a single jerky golf swing or incorrect use of exercise equipment (especially free weights, nautilus, and rowing machines) can cause serious back injuries.

The way a person moves, stands, or sleeps plays a major role in back pain.

Maintaining good posture is very important. This means keeping the ears, shoulders, and hips in a straight line with the head up and stomach pulled in. It is best not to stand for long periods of time. If it is necessary, walk as much as possible and wear shoes without heels, preferably with cushioned soles. Use a low foot stool and alternate resting each foot on top of it.
Sitting puts the most pressure on the back. Chairs should either have straight backs or low-back support. If possible, chairs should swivel to avoid twisting at the waist, have arm rests, and adjustable backs. While sitting, the knees should be a little higher than the hip, so a low stool or hassock is useful to put the feet on. A small pillow or rolled towel behind the lower back helps relieve pressure while either sitting or driving.
Riding in and driving a car for long periods of time increases stress. Move the car seat as far forward as possible to avoid bending forward. The back of the seat should not be reclined more than 30 degrees. If possible, the seat bottom should be tilted slightly upward in front. A traveler should stop and walk around about every hour. Avoid lifting or carrying objects immediately after the ride.

Anyone who engages in heavy lifting should take precautions when lifting and bending.

If an object is too heavy or awkward, get help.
Spread your feet apart to give a wide base of support.
Stand as close as possible to the object being lifted.
Bend at the knees, not at the waist. As you move up and down, tighten stomach muscles and tuck buttocks in so that the pelvis is rolled under and the spine remains in a natural "S' curve. (Even when not lifting an object, always try to use this posture when stooping down.)
Hold objects close to the body to reduce the load on the back.
Lift using the leg muscles, not those in the back.
Stand up without bending forward from the waist.
Never twist from the waist while bending or lifting any heavy object. If you need to move an object to one side, point your toes in that direction and pivot toward it.
If an object can be moved without lifting, pull it, don't push.

There are four natural curves in the spinal column: the cervical, thoracic, lumbar, and sacral curvature. The curves, along with the intervertebral disks, help to absorb and distribute stresses that occur from everyday activities such as walking or from more intense activities such as running and jumping.

Resources

www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.aaos.org -- American Academy of Orthopaedic Surgeons
www.arthritis.org -- Arthritis Foundation
www.spine.org -- North American Spine Society
www.apta.org -- American Physical Therapy Association
www.ampainsoc.org -- American Pain Society
www.theacpa.org -- American Chronic Pain Association
www.iasp-pain.org -- International Association for the Study of Pain

References

Apkarian AV, Sosa Y, Sonty S, Levy RM, Harden RN, Parrish TB, et al. Chronic back pain is associated with decreased prefrontal and thalamic gray matter density. J Neurosci. 2004;24(46):10410-10415.

Fairbank J, Frost H, Wilson-MacDonald J, Yu LM, Barker K, Collins R; Spine Stabilisation Trial Group. Randomised controlled trial to compare surgical stabilisation of the lumbar spine with an intensive rehabilitation programme for patients with chronic low back pain: the MRC spine stabilisation trial. BMJ. 2005;330(7502):1233.

Filler AG, Haynes J, Jordan SE, Prager J, Villablanca JP, Farahani K, et al. Sciatica of nondisc origin and piriformis syndrome: diagnosis by magnetic resonance neurography and interventional magnetic resonance imaging with outcome study of resulting treatment. J Neurosurg Spine. 2005;2(2):99-115.

Freeman BJ, Fraser RD, Cain CM, Hall DJ, Chapple DC. A randomized, double-blind, controlled trial: intradiscal electrothermal therapy versus placebo for the treatment of chronic discogenic low back pain. Spine. 2005 Nov 1;30(21):2369-77; discussion 2378.

Friedrich M, Gittler G, Arendasy M, Friedrich KM. Long-term effect of a combined exercise and motivational program on the level of disability of patients with chronic low back pain. Spine. 2005;30(9):995-1000.

Frost H, Stewart-Brown S. Acupressure for low back pain. BMJ. 2006 Mar 25;332(7543):680-1.

Hayden JA, van Tulder MW, Malmivaara AV, Koes BW. Meta-analysis: exercise therapy for nonspecific low back pain. Ann Intern Med. 2005;142(9):765-775.

Hayden JA, van Tulder MW, Tomlinson G. Systematic review: strategies for using exercise therapy to improve outcomes in chronic low back pain. Ann Intern Med. 2005;142(9):776-785.

Mercado AC, Carroll LJ, Cassidy JD, Cote P. Passive coping is a risk factor for disabling neck or low back pain. Pain. 2005;117(1-2):51-57.

Melissas J, Kontakis G, Volakakis E, Tsepetis T, Alegakis A, Hadjipavlou A. The effect of surgical weight reduction on functional status in morbidly obese patients with low back pain. Obes Surg. 2005 Mar;15(3):378-81.

Pneumaticos SG, Chatziioannou SN, Hipp JA, Moore WH, Esses SI. Low back pain: prediction of short-term outcome of facet joint injection with bone scintigraphy. Radiology. 2006 Feb;238(2):693-8.

Ratcliffe J, Thomas KJ, MacPherson H, Brazier J. A randomised controlled trial of acupuncture care for persistent low back pain: cost effectiveness analysis. BMJ. 2006 Sep 23;333(7569):626.

Richardson SM, Curran JM, Chen R, et al. The differentiation of bone marrow mesenchymal stem cells into chondrocyte-like cells on poly-L-lactic acid (PLLA) scaffolds. Biomaterials. 2006 Aug;27(22):4069-78.

Sherman KJ, Cherkin DC, Erro J, Miglioretti DL, Deyo RA. Comparing Yoga, Exercise, and a Self-Care Book for Chronic Low Back Pain: A Randomized, Controlled Trial. Ann Intern Med. 2005; 143: 849 - 856.

Tao XG, Bernacki EJ. A randomized clinical trial of continuous low-level heat therapy for acute muscular low back pain in the workplace. J Occup Environ Med. 2005 Dec;47(12):1298-306.

Trout AT, Kallmes DF, Gray LA, Goodnature BA, Everson SL, Comstock BA, Jarvik JG. Evaluation of vertebroplasty with a validated outcome measure: the Roland-Morris Disability Questionnaire. Am J Neuroradiol. 2005 Nov-Dec;26(10):2652-7.

Review Date:
3/19/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Urinary incontinence

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

In This Report

Highlights
Introduction
Stress Incontinence
Urge Incontinence
Overflow Incontinence
Functional Incontinence
Risk Factors
Diagnosis
Prognosis
Treatment
Lifestyle Changes
Other Treatments
Behavioral Treatments
Medications
Surgery
Other Procedures
Catheters and Collection De...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Sling Procedure Versus Burch Colposuspension

The sling procedure is better than Burch colposuspension in treating stress incontinence but may cause more post-operative urinary complications, according to results from an important 2007 New England Journal of Medicine study. In the first large-scale clinical trial to directly compare these two types of surgery, 47% of women who underwent the sling procedure had no urinary incontinence 2 years after surgery, compared with 38% of women who received the Burch procedure. However, 63% of women who had the sling procedure (and 47% of women who underwent the Burch procedure) experienced urinary tract infections following surgery.

Oxybutynin May Cause Hallucinations

In 2007, the FDA investigated reports that oxybutynin (Detrol) may cause hallucinations, especially in children and older adults. Out of 202 reports of oxybutynin-related central nervous system side effects, hallucinations occurred in 27% of cases involving children and 25% of cases involving adults age 60 years and older. The FDA is considering adding stronger cautions about these risks to oxybutynin’s prescribing label.

Tamsulosin and Tolterodine Combination Treatment

For men with moderate-to-severe lower urinary tract symptoms, including overactive bladder, a combination of tamsulosin (Flomax) and tolterodine (Detrol) works better than either drug alone, according to a study published in 2006 in the Journal of the American Medical Association.

Researchers Investigating Stem Cell Treatment for Stress Incontinence

Muscle stem cell injections may eventually prove to be an effective treatment for stress incontinence, indicate several small studies. Doctors took tissue biopsies from patients’ arm muscles, then isolated and injected the muscle stem cells into areas surrounding the urethra. The injections helped strengthen sphincter muscles and improved bladder control. Researchers presented results of these studies at the 2007 American Urological Association annual meeting and the 2006 Radiological Society of North America annual meeting.

Introduction

Urinary incontinence is the inability to control urination. It may be temporary or permanent, and can result from a variety of problems in the urinary tract. Urinary incontinence is generally divided into four groups, according to the problem involved:

Stress incontinence
Urge incontinence
Overflow incontinence
Functional incontinence

Often, more than one type of incontinence is present, with about 40% of all cases falling into more than one category.

Because incontinence is a symptom, rather than a disease, it is often hard to determine the cause. In addition, a variety of conditions may be the cause.

The urinary system helps to maintain proper water and salt balance throughout the body:

The process of urination begins in the two kidneys, which process fluids and dissolve waste matter to produce urine.
Urine flows out of the kidneys into the bladder through two long tubes called ureters.
The bladder is a sac that acts as a reservoir for urine. It is covered with a membrane and enclosed in a powerful muscle called the detrusor. The bladder rests on top of the pelvic floor. This is a muscular structure similar to a sling running between the pubic bone in front to the base of the spine.
The bladder stores the urine until it is eliminated from the body via a tube called the urethra, which is the lowest part of the urinary tract. (In men it is enclosed in the penis. In women it leads directly out.)
The connection between the bladder and the urethra is called the bladder neck. Strong muscles called sphincter muscles encircle the bladder neck (the smooth internal sphincter muscles) and urethra (the fibrous external sphincter muscles).

Click the icon to see an animation about urination.

The Process of Urination

The process of urination is a combination of automatic and conscious muscle actions. There are two phases: the emptying phase and the filling and storage phase.

The Filling and Storage Phase. When a person has completed urination, the bladder is empty. This triggers the filling and storage phase, which includes both automatic and conscious actions.

Automatic Actions. The automatic signaling process in the brain relies on a pathway of nerve cells and chemical messengers (neurotransmitters) called the cholinergic and adrenergic systems. Important neurotransmitters include serotonin and noradrenaline. This pathway signals the detrusor muscle surrounding the bladder to relax. As the muscles relax, the bladder expands and allows urine to flow into it from the kidney. As the bladder fills to its capacity (about 8 - 16 oz of fluid) the nerves in the bladder send back signals of fullness to the spinal cord and the brain.
Conscious Actions. As the bladder swells, the person becomes conscious of a sensation of fullness. In response, the individual holds the urine back by voluntarily contracting the external sphincter muscles, the muscle group surrounding the urethra. These are the muscles that children learn to control during the toilet training process.

When the need to urinate becomes greater than one's ability to control it, urination (the emptying phase) begins.

The Emptying Phase. This phase also involves automatic and conscious actions.

Automatic Actions. When a person is ready to urinate, the nervous system initiates the voiding reflex. The nerves in the spinal cord (not the brain) signal the detrusor muscles to contract. At the same time, nerves are also telling the involuntary internal sphincter (a strong muscle encircling the bladder neck) to relax. With the bladder neck now open, the urine flows out of the bladder into the urethra.
Conscious Actions. Once the urine enters the urethra, a person consciously relaxes the external sphincter muscles, which allows urine to completely drain out from the bladder.

The female and male urinary tracts are relatively the same except for the length of the urethra.

Stress Incontinence

The primary symptom of stress incontinence is leakage due to activities that apply pressure to a full bladder. High-impact exercise poses the greatest risk for leaking. But stress incontinence can occur with even minor activities, such as:

Coughing
Sneezing
Laughing
Running (sometimes even standing can produce leakage)
Lifting

Leakage stops when the activity stops. If the condition persists, it is more likely to be urge incontinence.

Stress incontinence occurs because the internal sphincter does not close completely. In both men and women, the aging process causes a general weakening of the sphincter muscles and a decrease in bladder capacity. Causes of stress incontinence, however, may differ between men and women.

In women, stress incontinence is nearly always due to one or both of the following:

The urethra fails to close and becomes overly movable (urethral hypermobility).
The muscles around the bladder neck weaken (intrinsic sphincteric deficiency or ISD). Some experts believe that this problem is present to some degree in nearly all women with stress incontinence. (ISD can also occur in anyone from an inborn disorder or injury from surgery or radiation.)

Many women are prone to one or both of these problems, which can occur under the following circumstances:

Having had many children through vaginal deliveries. In such cases, pregnancy and childbirth strain the muscles of the pelvic floor. Prolapsed uterus, in which the uterus protrudes into the vagina, occurs in about half of all women who have given birth. This condition can often cause incontinence.
Menopause. Estrogen deficiencies after menopause can cause the urethra to thin out so that it may not close properly.

Urethral Hypermobility. In urethral hypermobility the urethra does not close properly, allowing it to move too much (hypermobile). This condition typically occurs when the pelvic floor muscles in women become weak, and the following events occur:

The weakened pelvic floor muscles stretch.
This allows the bladder to sag downward within the abdomen.
The sagging bladder pulls on the muscles surrounding the bladder neck (internal sphincter), which are connected to the urethra.

Stress incontinence associated with urethral hypermobility is sometimes categorized as type 1 or type 2.

Type 1 is the less severe form, and the bladder neck and urethra remain incompletely closed.
In type 2, the angle of the bladder neck shifts. In such cases cystocele may occur, in which the bladder muscles bulge (herniate) into the vaginal wall.

Intrinsic sphincteric deficiency (ISD). Intrinsic sphincter deficiency (sometimes called type 3) is the other major cause of stress incontinence in women. It occurs when the bladder neck muscles are damaged or weakened. The result is twofold:

The bladder neck is open during filling.
The closing pressure around the urethra is low.

This is the most severe stress incontinence in women and usually occurs after previous surgeries for incontinence.

Prostate treatments can impair the sphincter muscles. Such treatments are the major causes of stress incontinence in men. They include the following:

Surgery or radiation for prostate cancer. Incontinence occurs in nearly all male patients for the first 3 - 6 months after radical prostatectomy. After a year of the procedure, most men retain continence, although leakage can occur.

Surgery for benign prostatic hyperplasia. Stress incontinence occurs in 1 - 5% of men after transurethral resection of the prostate (TURP), the standard treatment for severe benign prostatic hyperplasia.

Click the icon to see an illustrated series detailing TURP surgery.

Incontinence after prostate procedures is often a combination of urge and stress. Because studies often combine the two types of incontinence, it is not always clear which predominates.

Urge Incontinence

The main symptom of urge incontinence (also called hyperactive, irritable, or overactive bladder) is the need to urinate frequently. Patients may go to the bathroom more than 8 times over 24 hours, including 2 or more times a night, and have subsequent leakage. However, most people (60%) with overactive bladder experience only urgency and frequency. In some cases, urge incontinence occurs only at night. This is called nocturnal enuresis.

All cases of urge incontinence involve an overactive bladder. This occurs when the detrusor muscle, which surrounds the bladder, contracts inappropriately during the filling stage. When this occurs, the urge to urinate cannot be voluntarily suppressed, even temporarily. There is usually one of two types:

Idiopathic Detrusor Overactivity (formerly called Detrusor Instability). In this type, the nerves serving the bladder have signaled the brain appropriately that the bladder is full, but the detrusor muscles are unable to be suppressed. The actual cause, however, is not known.
Neurogenic Detrusor Overactivity (formerly called Detrusor Hyperreflexia). With this type, a known neurologic abnormality impairs the signaling systems between the bladder and the central nervous system, and the brain is unable to inhibit the detrusor muscles controlling urination.

Very often, the cause of detrusor instability and bladder hyperactivity is unknown. Some conditions that can produce the disorders leading to urge incontinence include the following:

Benign prostatic hyperplasia (BPH). Detrusor instability occurs in about 75% of men with BPH and causes frequency, urgency, and urination during the night (although incontinence itself occurs only in very severe cases). Urge incontinence only at night can be a sign of severe obstruction in the urinary tract.

Benign prostatic hypertrophy (BPH) is a non-cancerous enlargement of the prostate gland, commonly found in men over the age of 50.

Prostate surgical procedures. Either prostatectomy for prostate cancer or transurethral resection of the prostate (TURP) for BPH can cause detrusor instability. As with stress incontinence, prostatectomy poses a much higher rate than with TURP, which is very low.
Hysterectomy. Complications of this operation, which removes the uterus, are associated with a higher risk for urge incontinence. In one study, for example, incontinence developed or worsened after hysterectomy in about 16% of women who had only mild or no incontinence before surgery. However, hysterectomies can also significantly improve urinary incontinence in many women who have an existing condition before the procedure. In the same study, 30% of women had severe urinary incontinence before hysterectomy, which declined to 20% afterward and was sustained for at least 2 years.

Click the icon to see an image about hysterectomy.

Damage to the central nervous system. Certain neurologic disorders or injuries can disrupt the passage of nerve messages between the urinary tract and central nervous system. These neurological conditions include stroke, multiple sclerosis, spinal cord or disk injury, and Parkinson's disease.
Infections.
The aging process.
Emotional disorders. Anxiety and possibly even depression have been associated with urge incontinence.
Medications, including some sleeping pills.
Genetic factors may play a role in some cases.

Overflow Incontinence

Overflow incontinence happens when the normal flow of urine is blocked and the bladder cannot empty completely. Overflow incontinence can be due to a number of conditions:

A partial obstruction. In this case the urine cannot flow completely out of the bladder, so it never fully empties.
An inactive bladder muscle. In contrast to urge incontinence, the bladder is less active than normal, not more. It cannot empty properly and so becomes distended, or swells. Eventually this distention stretches the internal sphincter until it opens partially and leakage occurs.

The causes of the conditions leading to overflow incontinence include:

Tumors
Certain medications (anticholinergics, antidepressants, antipsychotics, sedatives, narcotics, alpha-adrenergic agonists, beta-adrenergic agonists, calcium channel blockers)
Benign prostatic hyperplasia (enlarged prostate)
Scar tissue
Nerve damage. In such cases, nerves in the bladder are damaged so that the body cannot feel when the bladder is full, and the bladder does not contract. Such damage can be caused by spinal cord injuries, previous surgery in the colon or rectum, and pelvic fractures. Diabetes, multiple sclerosis, and shingles also can cause this problem.

Functional Incontinence

Patients with functional incontinence have mental or physical disabilities that keep them from urinating, although the urinary system itself is normal. Conditions that can lead to function incontinence include:

Parkinson's disease.
Alzheimer's disease and other forms of dementia. Mental confusion may prevent both recognition of the need to void and locating a bathroom.
Severe depression. In such cases, people may become incontinent because they are indifferent to self-control.

Risk Factors

About 13 million adults experience incontinence at some time. The number, however, may actually be higher because most patients are reluctant to discuss incontinence with their doctors. In fact, research indicates that many patients will not admit to having the problem even when questioned directly. Although a third of American men and women age 30 - 70 have experienced at least some loss of bladder control, most have not been diagnosed by a doctor.

A 2004 survey of more than 1,400 Americans found that despite the prevalence of bladder control loss, an alarming 64% of those experiencing symptoms are not currently taking measures to manage their condition. The survey, sponsored by the National Association for Continence, also found that adults waited an average of 6 years before discussing their symptoms with a doctor. A 2006 study reported that only half of women with urinary incontinence have discussed their condition with a doctor, while only a third had received any treatment.

Incontinence is uncommon in children 5 years and older. However, it may still occur in:

10% of 5 year-olds
5% of 10 year-olds
1% of 18 year-olds

Incontinence that occurs before puberty is twice as common in boys as in girls. Most young people who experience nighttime wetting do not have any serious physical or emotional disorders. It is often difficult to diagnose incontinence in children. Many cases result from a combination of factors, including:

Birth defects or inborn conditions that cause problems in the urinary tract
Slower physical development
An overproduction of urine at night
A lack of ability to recognize bladder filling when asleep
Anxiety
Inherited factors (indicated by a strong family history of bedwetting)

Bedwetting in children is not considered incontinence. However, bedwetting and other urinary problems in childhood may predict the later development of adult urinary incontinence. According to a 2006 study, women who experienced childhood bedwetting, as well as frequent daytime and nighttime urination, had an increased risk of developing adult urge incontinence.

All older adults are susceptible to incontinence. One in 10 people over age 65 have some type of bladder control loss. About 12% of women ages 60 - 64 and 21% of women age 85 and over experience daily urinary incontinence. About half of the elderly who are housebound or in nursing homes experience incontinence.

Urinary incontinence is far more common among women than men. Between 15 - 50% of women experience urinary incontinence during their lifetimes, with the highest rates occurring in women who have had children. Severe urinary continence affects 7 – 10% of women. About 10% of women undergo surgery for urinary incontinence or pelvic organ prolapse.

Birth Conditions. Pregnancy and childbirth may increase the risk for urinary incontinence. The risk is highest with the first child, and there is an increased risk in women who have their first child over age 30. Some studies suggest that women who used the drug oxytocin for inducing labor are at higher risk for developing urinary incontinence. Such medically induced labor tends to subject the muscles and nerves in the pelvis to greater force than does natural labor.

Studies indicate that the method of birth can affect risk later in life. For example, a major 2003 study reported that women who had a cesarean section had a much lower risk for stress incontinence before age 50 than women who had vaginal delivery. However, a 2006 study contradicted many assumptions by suggesting that vaginal delivery is not associated with later development of urinary incontinence in postmenopausal women. The study compared sisters who had either given birth vaginally or had never had children. Researchers found no difference in rates of urinary incontinence. The study suggested that cesarean delivery may not make much difference in preventing urinary incontinence.

Another 2006 study found that episiotomy does not help prevent urinary incontinence. Episiotomy is a surgical incision that is made during childbirth to the perineum, the muscle between the vagina and the rectum. Doctors commonly perform this procedure to help widen the vaginal opening and prevent tearing. The study found that episiotomy does not have many benefits, and may later cause pain during intercourse.

Vaginal birth can cause pelvic prolapse, a condition in which pelvic muscles weaken and the pelvic organs (bladder, uterus) slip into the vaginal canal. Pelvic prolapse, and the surgery used to correct it, can cause incontinence. Sacrocolpopexy is the standard surgical procedure for repairing pelvic prolapse. A 2006 study found that performing a urinary incontinence surgical procedure (Burch colposuspension) at the same time as sacrocolpopexy can help prevent stress incontinence. [See Surgery section.]

High-Impact Exercise. Women who engage in high-impact exercise are susceptible to urinary leakage, particularly women with a low foot arch. Shock to the pelvic area is increased as the foot makes impact with hard surfaces. Those at highest risk for urinary leakage are gymnasts, followed by softball, volleyball, and basketball players.

Smokers. Studies have reported a higher risk for incontinence, notably mixed incontinence, in women who are current or former heavy smokers (more than a pack a day).

Obesity. Being overweight is a major risk factor for all types of incontinence. The more a woman weighs, the greater her risk.

Medical Factors in Older Women. Urge incontinence is more common among postmenopausal women who have a history of:

Diabetes
Higher body mass index (heavier weight)
Hysterectomy
Two or more urinary tract infections within the past year

The rate of incontinence in men (about 1.5 - 5%) is much lower than in women. The risk for urinary incontinence increases with age. In the United States, about 17% of men over age 60 have urinary incontinence. In older men, prostate problems and their treatments are the most common factors that affect the urinary tract. Up to 30% of men who have had surgery to remove their prostate gland experience some degree of urinary incontinence.

Urinary incontinence varies by race and ethnicity. It is most common in non-Hispanic white women. Among men, African-Americans are at highest risk. Some studies suggest that the greatest disparity is with stress incontinence. African-American and Asian American women have a much lower risk for stress incontinence than Caucasian and Hispanic women.

A number of conditions can cause temporary incontinence in anyone:

Urinary tract infections
Excess fluid intake
Constipation
Severe depression
Restricted mobility

Drugs. Drugs are most often the cause of temporary incontinence.

Drugs that affect the adrenergic system (a nerve-cell and hormonal pathway that regulates the sphincter muscle) are common causes of incontinence. For example, alpha-adrenergic blockers, such as terazosin (Hytrin), used for benign prostatic hypertrophy, can cause incontinence by over-relaxing the muscles. On the other hand, men with enlarged prostates who suffer from urinary problems may be helped by the increase of urine flow after using terazosin.
Alpha-adrenergic agonists, such as pseudoephedrine (found in some oral decongestants) strengthen the muscles and may cause overflow incontinence in susceptible people.
Beta-adrenergic blockers, such as propranolol (Inderal), prescribed for hypertension and angina, relax the sphincter.
Diuretics, used for high blood pressure, often rapidly introduce high urine volumes into the bladder.
Calcium-channel blockers can cause overflow incontinence by relaxing the bladder detrusor muscles.
Colchicine, a drug used for gout, can cause urge incontinence.
Other medications and substances that increase the risk for incontinence are caffeine, sedatives, antidepressants, antipsychotics, and antihistamines.

Diagnosis

Fewer than half of the patients who have urinary incontinence tell their doctor about the problem. In many cases, patients simply feel that incontinence is part of the aging process. And, in spite of the commonness of this problem, two-thirds of doctors never ask their older patients if they experience incontinence.

It is important, however, for both the doctor and the patient to raise the issue.

The first step in the diagnosis of incontinence is a detailed history. The doctor should ask questions about the patient's present and past medical conditions and patterns of urination. Patients should tell the doctor the following information:

When the problem began
Frequency of urination
Amount of daily fluid intake
Use of caffeine or alcohol
Frequency and description of leakage or urine loss, including activity at the time, sensation of urge to urinate, and approximate volume of urine lost
Frequency of urination during the night
Whether the bladder feels empty after urinating
Pain or burning during urination
Problems starting or stopping the flow of urine
Forcefulness of the urine stream
Presence of blood, unusual odor or color in the urine
A list of major surgeries with their dates, including pregnancies and deliveries, and other medical conditions
Any medications being taken

A 2006 study suggested a simpler way of diagnosing incontinence using a test that asks 3 questions:

During the last 3 months, have you leaked urine (even a small amount)?
When did you leak urine? (During physical activity; when you could not reach the bathroom quickly enough; without physical activity or bladder urge.)
When did you leak urine most often? (Physical activity; bladder urge; without or about equally with physical activity or bladder urge.)

Based on the patient’s answers, the “3IQ” test may help a doctor distinguish between urge and stress urinary incontinence.

Voiding Diary. The patient might find it helpful to keep a diary for 3 to 4 days before the office visit. This diary, sometimes referred to as a voiding diary or log, should be a detailed record of:

Daily eating and drinking habits
The times and amounts of normal urination

For each incident of incontinence, the log should also detail:

The amount of urine lost (the patient is often asked to catch and measure urine in a measuring cup during a 24-hour period)
Whether the urge to urinate was present
Whether the patient was involved in physical activity at the time

The office visit should consist of a thorough physical examination, checking for abnormalities or enlargements in the rectal, genital, and abdominal areas that may cause or contribute to the problem.

One of the important measurements for urinary incontinence is the postvoid residual urine volume (PVR). This is the amount of urine left in the bladder after urination:

Normally, about 50 mL or less of urine is left
More than 100 mL suggests an abnormality and requires further tests
More than 200 mL is a definite sign of abnormalities

Use of a Catheter. The most common method for measuring PVR uses a catheter, which is inserted into the urethra after a few minutes of urination. The advantage of the catheter is that it can also collect urine for analysis.

Ultrasound. Ultrasound is useful in determining the volume of urine.

Cystometry measures the bladder's ability to retain urine at different capacities and pressures. It uses a catheter and can be performed at the same time as the PVR test.

Subtraction Cystometry. Although procedures vary, the basic steps for the technique are as follows:

The patient empties the bladder as much as possible.
Two catheters are inserted into the urethra until they reach the bladder. One is used to fill the bladder with water. The other is used to measure pressure. Another catheter is inserted into the rectum or vagina, which is used to measure abdominal pressure.
While water is instilled through the tube into the bladder, the pressure in the bladder and abdomen are measured and the results are recorded in a computing device.
During the process, the patient informs the doctor about any changes in the need to urinate, including the initial need to urinate, a normal desire to urinate, and a strong need to urinate.
Often during this process, the patient is asked to cough, bounce up and down, or even walk in place. The patient may also be asked to strain as if he or she is having a bowel movement. This is called the Valsalva maneuver. The point at which leakage occurs during this action is called the Valsalva leak point pressure, which might be a useful measurement for determining treatment.
When the urge to urinate is strong, the doctor stops this portion of the test.
A calculation is then made using bladder and abdominal pressure measurements as well as volume and flow rate of the urine. The result provides the doctor with an assessment of detrusor contractions.

The detrusor muscles of a normal bladder will not contract during bladder filling. Severe contractions at low amounts of administered fluid (less than 200 mL) indicate urge incontinence. Stress incontinence is suspected when there is no significant increase in bladder pressure or detrusor muscle contractions during filling, but the patient experiences leakage if abdominal pressure increases.

Video Cystometry. Video cystometry combines a computer reading of bladder pressures and pictures of the bladder itself. It is most useful in cases where the more standard tests have not yielded satisfactory results.

To determine whether the bladder is obstructed, the speed of urine flow is measured electronically using a test called uroflowmetry. The test involves the following steps:

Patients are instructed not to urinate for several hours before the test and to drink plenty of fluids so they have a full bladder and a strong urge to urinate.
To perform this test, a patient urinates into a special toilet equipped with a uroflowmeter.
It is important that patients remain still while urinating to help ensure accuracy, and that they urinate normally and do not exert strain to empty their bladder or attempt to retard their urine flow.

Many factors can affect urine flow (such as straining or holding back because of self-consciousness) so experts recommend that the test be repeated at least twice.

Q[max]. The rate of urine flow is calculated as milliliters of urine passed per second (mL/s). At its peak, the flow rate measurement is recorded and referred to as the Q[max]. The higher the Q[max], the better the patient's flow rate. Men with a Q[max] of less than 12 mL/s have four times the risk for urinary retention than men with a stronger urinary flow.

The Q[max] measurement is sometimes used as the basis for determining the severity of obstruction and for judging the success of treatments. It is not very accurate, however, for a number of reasons:

Urine flow varies widely among individuals as well as from test to test.
The patient's age must be considered. Flow rate normally decreases as men age, so the Q[max] typically ranges from more than 25 mL/s in young men to less than 10 mL/s in elderly men.

The Q[max] level does not necessarily coincide with a patient's perceptions of the severity of his own symptoms.

Urethrocystoscopy. Urethrocystoscopy, also called cystourethroscopy or cystoscopy, detects structural abnormalities, inflammation of the bladder wall, or masses that might not show up on x-ray.

The patient is given a light anesthetic, and the bladder is filled with water.
Next, a thin flexible tube called a cystoscope is inserted through the urethra into the bladder.
The end of the cystoscope contains a tiny microscope-like instrument.
The doctor uses the cystoscope to look for abnormalities in the interior of the bladder.

Cystoscopy is a procedure that uses a flexible fiber optic scope, which is inserted through the urethra into the urinary bladder. The doctor fills the bladder with water and inspects the interior of the bladder. The image seen through the cystoscope may also be viewed on a color monitor and recorded on videotape for later evaluation.

The procedure has some risks. Complications are uncommon, but can include allergic response to the anesthetic, urinary tract infection, bleeding, and urine retention.

Intravenous Pyelogram. Intravenous pyelogram (IVP) may be used to diagnose urge incontinence. It is performed as follows:

A dye is injected into the patient's vein and is processed by the kidneys.
A series of x-ray pictures are taken of the kidneys, ureter, and bladder as the dye passes through them. This provides a dynamic picture of the relationship between the patient's urinary system and urinary functioning.

Click the icon to see an image of an intravenous pyelogram.

IVPs can detect structural abnormalities, urethral narrowing, or incomplete emptying of the bladder. This test should not be used on pregnant women or patients with kidney failure. There is a risk for an allergic reaction to standard dyes, although newer, less allergenic ones are becoming available.

Ultrasound. Ultrasound plays a role in many cases of incontinence. For example, it is useful for men with prostate problems. It is helpful in measuring urine volume in the bladder. Ultrasound may also be useful in many cases of female stress incontinence, by identifying abnormalities in the bladder neck, and in assessing the urinary tract before and after surgery. It also may eventually be useful in diagnosing detrusor instability.

Chain Cystogram. In cases of stress incontinence, a chain cystogram may also be performed. With this procedure, a beaded chain is positioned in the bladder and urethra. The x-ray image of the chain reveals the angle of the bladder neck. This test should not be performed on pregnant women.

Electrophysiologic sphincter testing, also referred to as electromyography (EMG), evaluates two important factors:

The function of the nerves serving the sphincter and pelvic floor muscles.
The patient's ability to control these muscles.

Using a technique similar to that of an electrocardiogram, the doctor places electrodes on the affected areas to observe electrical activity in the muscles.

Urethral pressure profile is used to investigate urethral blockage. A probe is placed in the urethra to determine pressure at different points along this pathway during urination and the exact location of any obstruction in the urethra.

Prognosis

Incontinence is rarely life threatening. In most cases, if treated promptly, physical complications are not serious.

Urinary incontinence can have severe emotional effects. Depression is very common in women with incontinence. For example, in a 2003 study, 82% of women with severe incontinence and 41% of those with moderate incontinence reported at least 2 weeks of depression during the preceding year. Incontinence also has emotional effects on men. A number of studies of prostate cancer patients suggest that incontinence is a much more distressing side effect for men than impotence (also a side effect of prostate cancer treatment).

Other negative emotional effects reported include:

Loneliness and humiliation. Because little public attention has been paid to this problem, the incontinent person often feels alone and humiliated. Many people with incontinence do not even seek medical advice for the problem. In one survey of doctors, nearly all of them reported that a patient's embarrassment and reluctance to discuss bladder problems is a major barrier to successful treatment.
Shame. Many people experience a sense of personal failure.
Helplessness. Patients often feel helpless and angry.
Introversion. Patients may eventually curtail social activities, or even give them up entirely.
Lack of confidence. Many people with incontinence believe that they are unemployable.

To prevent humiliation due to wetness or odors, people with incontinence may have to alter their way of life.

Errands become very difficult and need advanced planning.
Public bathrooms may difficult to locate or unavailable. The problem is particularly severe for those with urge incontinence who have little time to reach a bathroom and have large volume spills.

Incontinence is particularly serious in older adults:

Older adults who are otherwise healthy may stop exercising because of leakage, which can increase their impairment.
Incontinence can result in loss of independence and quality of life.
It is a major reason for nursing home placement.
Severe incontinence may require catheterization. This is the insertion of a tube that allows urine to continually pass into an external collecting bag. In such cases, complications are common, particularly infections.
There is a strong association between urge incontinence and falls and injuries. In one large study, over half of women who reported incontinence experienced at least one fall over a 3-year period. This high incidence of falls may be due in part to the rush to the toilet in the middle of the night. Keeping a pan or portable commode near the bed may prevent injuries as well as improve sleep and general convenience.

Treatment

The treatment for temporary incontinence can be rapid, simple, and effective. If urinary tract infections are the cause, they can be treated with antibiotics. Any related incontinence will often clear up in a short time. Medications that cause incontinence can be discontinued or changed to halt episodes.

Chronic incontinence may require a variety of treatments, depending on the cause. Treatment options are listed below in the order in which they are usually tried, from least-to-most invasive:

Behavioral techniques, which include Kegel exercises and bladder training, are sometimes all a person needs for achieving continence. A number of devices can also be used to strengthen muscles and prevent urine leakage. Bladder training is useful for urge incontinence.
Medications are tried next. These may include anticholinergics and antispasmodics. Estrogen or estrogen plus progesterone used to be recommended, but recent research has shown that these hormone treatments can actually make urinary incontinence worse.
Surgery. Surgery is the last resort; there are many effective procedures available for stress incontinence.

Lifestyle techniques to improve quality of life and improve hygiene are part of all treatments.

Lifestyle measures, including dietary recommendations, bladder training, and continent aids, are useful for anyone with incontinence. Other treatments vary depending on whether the patient has stress or urge incontinence. In people who have both, the treatment usually is aimed at the predominant form.

Treating Stress Incontinence. The general goal for women with stress incontinence is to strengthen the pelvic muscles. Typical steps for treating women with type 1 stress incontinence are:

Devices and continent aids for blocking urine in the urethra (vaginal pessaries, adhesive pads, and others).
Behavioral techniques and noninvasive devices, including Kegel exercises, weighted vaginal cones, and biofeedback.
Medications. Alpha-adrenergic agonists and possibly tricyclic antidepressants.
Surgery is a reasonable option if symptoms do not improve with noninvasive methods. Many are available, and most are designed to restore the bladder neck and urethra to their anatomically correct positions.

Treating Urge Incontinence. The goal of most treatments for urge incontinence is to reduce the hyperactivity of the bladder. The following methods may be helpful:

Behavioral methods
Medications (anticholinergics, anti-spasmodics, and alpha blockers)
Procedures that stimulate the pelvic floor or nerves in the tailbone (the sacral nerves), which help retrain the bladder

Lifestyle Changes

Many products are now available that help patients avoid embarrassment and, in some cases, prevent leakage. With recent improvements in paper technology, pads are now thin enough to be worn undetected, and a spare can be hidden in a purse or pocket. Proper hygiene is also essential for patients with incontinence.

Keeping Skin Clean. To avoid skin irritation and infection associated with incontinence, keep the area around the urethra clean. The following tips may be helpful:

After a urinary accident, clean any affected areas right away.
When bathing, use warm water and don't scrub forcefully; hot water and scrubbing can injure the skin.
A number of cleansers are available that are specially created for incontinence and allow frequent cleansing without over-drying or causing irritation to the skin. Most do not have to be rinsed off; the area is simply wiped with a cloth.
After bathing, a moisturizer plus a barrier cream should be applied. Barrier creams include petroleum jelly, zinc oxide, cocoa butter, kaolin, lanolin, or paraffin. These products are water repellent and protect the skin from urine.
Anti-fungal creams that contain miconazole nitrate are used for yeast infections.

Preventing or Reducing Odor. Certain methods may help reduce odor from accidents. They include:

Deodorizing tablets, such as Derifil, Nullo, Devrom, and Chlorofresh can be taken by mouth or used in appliances. Most contain chlorophyll.
Taking an alfalfa pill four times a day may reduce odor, and is not believed to interfere with any other medications. Alfalfa is a common grass, and some people with seasonal allergies may experience an allergic reaction. Talk to your doctor before taking any type of supplement.
Drinking more water, not less, will also reduce odors. Drinking more water may actually help reduce leakage, too.
To remove odors from mattresses, some experts recommend a solution of equal parts vinegar to water. Once the mattress has dried, baking soda can be applied on the stain, rubbed in, and then vacuumed off.

Weight Control. In women, pelvic floor muscle tone weakens with significant weight gain, so women are urged to eat healthy foods in moderation and to exercise regularly.

Fluid Intake. A common misconception among people with incontinence is that drinking less water will prevent accidents. In reality, limiting fluid intake has the following effects:

The lining of the urethra and bladder becomes irritated, which may actually increase leakage.
Concentrated urine also has a stronger pungency, so drinking plenty of fluids can help reduce odor.

Some experts recommend drinking two to three quarts a day.

Drinking plenty of cranberry juice may be particularly helpful. It is known to help prevent urinary tract infections. (Low calorie juices are available.)

People with incontinence, however, should stop drinking beverages 2 - 4 hours before going to bed, particularly those who experience leakage or accidents during the night.

Fiber-Rich Foods. Constipation can worsen urinary incontinence, so diets should be high in fiber, fruits, and vegetables.

Fluid and Food Restrictions. A number of foods and beverages may increase incontinence. Some experts suggest that people who eat or drink the following items should try eliminating one a day over a 10-day period and check to see if removing them improves continence:

Caffeinated beverages. (In one major 2003 study, tea drinking -- but not coffee drinking -- was associated with incontinence. In general, however, it might be useful to try avoiding coffee as well, including decaf coffee.)
Carbonated beverages such as soda
Alcoholic beverages
Citrus fruits and juices
Tomatoes and tomato-based foods
Spicy foods
Chocolate
Sugars and honey
Artificial sweeteners
Milk and milk products

Some otherwise healthy adults stop exercising because of leakage. There are a number of methods for preventing or stopping leakage during exercise. The following are some tips:

Limit fluid intake before exercising (but be sure not to become dehydrated)
Urinate frequently, including right before exercise
Women can try wearing pads or urethral inserts

A variety of absorbent pads and undergarments are quite effective in catching spills and leaks. Many undergarments developed for incontinence are almost indistinguishable from regular briefs and underpants.

For women, the following are available:

Normal and even attractive looking washable underwear that contains waterproof panels is available for women. Even stomach-control panties are available for women with incontinence.

For men, the following are available:

Drip collectors are available which can be worn under briefs and are not noticeable under normal clothing. Lined with absorbent material, the pouch-like collector surrounds the penis or scrotum and is fastened with a belt or pins.
Washable briefs made from polyester have a fully functional fly and waterproof panel and look and feel like normal underwear. Boxer shorts are also available that look regular but have a protective pouch.

Even for men and women with severe incontinence, disposable undergarments can be purchased that have a normal look to them.

All absorbent undergarments should be changed when wet to limit problems of chafing or infection.

A specially shaped plastic urinal (Feminal) is available for women. It avoids the use of a bedpan, and can be used while the woman is lying down, seated, or even standing.

Urinals for men are available that attach to athletic-like supporters.

Other Treatments

Foam pads (Miniguard, UroMed, Impress, Softpatch) with an adhesive coating have been developed for women with stress incontinence. They work as follows:

The pad is placed over the opening of the urethra where it creates a seal, preventing leakage.
It is removed before urinating and replaced with a new one afterwards.
The pad can be worn up to 5 hours a day and through the night.
It can be used during physical activity, although it may change position during vigorous exercise.
It should not be worn during sexual intercourse.

In one study of women who used these products, the average number of leaks per week dropped from 14 to 5. Women with more severe incontinence (an average of 34 leaks a week) had only 10 events, and when leakage occurred, it was slight.

Adhesive pads should not be used by women with the following conditions:

Urinary tract or vaginal infections
Urge or other forms of nonstress incontinence
A history of surgery for incontinence

Urethral Shields. Shields or caps (CapSure, Bard Cap Sure, FemAssist) that fit over the urethral opening are safe and effective in managing many forms of incontinence.

In a study of patients with stress incontinence, CapSure reduced urine loss by 96% within a week, and 82% of patients were completely dry. Side effects include irritation and urinary tract infections, although they are not severe.
In another study, 47% of women who used FemAssist reported complete continence, and 33% of the women reported continence was improved by more than half. FemAssist offered equal benefits for women with stress, urge, or mixed incontinence.

Urethral Tubes or Sleeves. Tubes or sleeves (Reliance Urinary Control Device, FemSoft) that fit into the urethra are also available for female incontinence.

The Reliance Urinary Control Device for women is a small tube inserted into the urethra using a reusable syringe. The device must be prescribed by a doctor, who measures the woman's urethra to determine the right size. The tip of the tube contains a balloon that is inflated against the urethra and blocks urine, preventing leakage. Every time a woman urinates, she pulls a string that deflates the balloon, then throws the old device away and replaces it with a new one. It is effective, but carries a high risk for urinary tract infections and most women report discomfort and irritation.
FemSoft is a silicone tube insert surrounded by a liquid-filled sleeve. When the tube is inserted into the urethra, the sleeve conforms to its shape and creates a seal at the bladder neck, preventing leakage. It is intended for one-time use and is replaced after voiding. This is a relatively new product and information is lacking on its comfort and risk for urinary tract infections.

Vaginal Devices. Devices that support the vaginal wall also help support the urethra that is located next to it:

Tampons. Mild stress incontinence in women, particularly when induced by exercise, may be managed by using a tampon. Specially designed tampons (such as the Contrelle Continence Tampon) are available, but even simple menstrual tampons may be helpful. (Keep in mind that tampons can only be worn for a few hours.) As tampons push on the vaginal wall, it compresses the urethra. In one study, 86% of women with mild incontinence remained continent during exercise sessions when using tampons. Out of this group, however, only 29% with severe incontinence remained dry.
Vaginal Pessaries. Vaginal pessaries are devices inserted into the vagina that support the inside of the vaginal walls. Pessaries are usually made of silicon and come in various forms, including donut or cube-shapes. They must be fitted by a health professional and are effective for vaginal prolapse or other vaginal structural problems. Serious complications are rare but can occur if the pessary is not replaced periodically.
Introl Bladder Neck Support. The Introl bladder neck support prosthesis is a flexible ring that is inserted into the vagina and has two ridges that press against the walls, supporting the urethra. Sizing the Introl is difficult, but success rates of 83% have been reported in women with stress incontinence. It can be left in during urination but must be removed and cleaned afterward. Introl can cause vaginal or urethral infections and may also be uncomfortable.

Behavioral Treatments

With the exception of functional incontinence, most cases of incontinence will almost always improve with behavioral techniques. There are a variety of methods, but the focus is usually on strengthening or retraining the bladder. Studies indicate that such exercises are very effective, even for men recovering from surgery for prostate cancer.

To enhance bladder training for incontinent patients who are in nursing rooms, nurses may need to check patients for dryness and regularly remind them to urinate. As an extra tip for older people with severe incontinence, keeping a pan or portable commode near the bed may prevent injuries from falling as well as improve general convenience.

Perhaps the best first-line approach for any form of incontinence is a combination of Kegel exercises and bladder training. In one study, women who used this combination approach experienced an average 50% reduction in incontinence episodes, with nearly 40% of them achieving complete continence. It was equally effective for urge, stress, or mixed incontinence.

Studies also report that between 50 - 75% of patients who perform only Kegel exercises experience a substantial improvement in their symptoms, including elderly people who have had the problem for years. A 2006 review suggested that Kegel exercises are especially helpful for women in their 40s and 50s who suffer from stress incontinence. The women participated in a supervised Kegel exercise program for at least 3 months.

Pelvic Floor Muscle (Kegel) Exercises. Kegel exercises are designed to strengthen the muscles of the pelvic floor that support the bladder and close the sphincters.

Stress incontinence is an involuntary loss of control of urine that occurs at the same time abdominal pressure is increased as in coughing or sneezing. It develops when the muscles of the pelvic floor have become weak.

Dr. Kegel first developed these exercises to assist women before and after childbirth, but they are very useful in helping to improve continence for both men and women. Kegel exercises are particularly useful for the following conditions:

Stress incontinence. Some experts believe that Kegel exercises should be the primary treatment for stress incontinence.
Urge incontinence. They can also be helpful for urge incontinence in cases that are not caused by nerve damage. In one study, 85% of women reported satisfaction with this program.

The general approach for learning and practicing Kegel exercises is as follows:

Since the muscles are sometimes difficult to isolate, the best method is to first learn while urinating. The patient begins to urinate and then contracts the muscle in the pelvic area with intention of slowing or stopping the flow of urine. Women should contract the vaginal muscles as well. They can detect this by inserting a finger inside the vagina. When the vaginal walls tighten, the pelvic muscles are being correctly contracted.
An alternate approach is to isolate the muscles used in Kegel contractions by sensing then squeezing and lifting the muscles in the rectum that are used in passing gas. (Again, women should contract the vaginal muscles as well.)
Patients should place their hands on their abdomen, thighs, and buttocks to make sure there is no movement in these areas while exercising.
In order to achieve success, some experts recommend performing two exercises that have different timing for the hold and release of the contraction. Both should be done regularly.
The first method is used for strengthening the pelvic floor muscles. The patient slowly contracts and lifts the muscles and holds for 5 seconds, then releases them. There is a rest of 10 seconds between contractions.
The second method is simply a quick contraction and release. The object of this exercise is to learn to shut off the urine flow rapidly.
In general, patients should perform 5 - 15 contractions, three to five times daily.

Some notes of caution:

Once learned, Kegel exercises should not be performed while urinating more than about twice a month, since this practice may eventually weaken the muscles.
In women, incorrect or overly vigorous exercises may cause vaginal muscles to tighten excessively, resulting in pain during sexual intercourse.
Over-exercise can also tire muscles and cause more leakage.
Incontinence will return to its original severity if these exercises are discontinued, so commitment to the program must be high and possibly life-long.
It may be several months before the patient sees significant improvement.

Bladder Training. Bladder training involves a specific, graduated schedule for increasing the time between urinations:

Patients start by planning short intervals between urinations, then gradually progressing with a goal of voiding every 3 - 4 hours.
If the urge to urinate arises between scheduled voidings, patients should remain in place until the urge subsides. At the time, the patient moves slowly to a bathroom. (In a small study, 73% of women with stress incontinence were helped by an absurdly simple and obvious movement: crossing the legs whenever a cough or sneeze was coming on.)

This system uses a set of weights to improve pelvic floor muscle control. The cones are inexpensive, relatively simple to use, and evidence suggests that they are as effective as Kegel exercises or electrostimulation:

The typical set includes five cones of graduated weights ranging from 20 grams (less than 1 ounce) to 65 grams (slightly over 2 ounces).
Starting with the lightest, the woman places the cone in her vagina while standing and attempts to prevent the cone from falling out. The muscles used to hold the cone are the same ones needed to improve continence.

As with standard Kegel exercises, frequent repetition is required, but most women will eventually be able to use the heavier weights and build up the ability to prevent stress and urge incontinence.

Women who are unable to learn Kegel muscle contraction and release with verbal instructions can be helped with the use of biofeedback:

Biofeedback uses a vaginal or rectal probe inserted by the patient that relays information to monitoring equipment.
The patient isolates the pelvic floor and bladder muscles and performs Kegel exercises.
The monitor emits auditory or visual signals that indicate how strongly the patient is contracting the proper pelvic floor muscles and how effectively the bladder muscles are being released.
The apparatus is designed for home use.

As with any Kegel exercise regimen, biofeedback must be used for several months before it is effective. In one major study, 75% of women with urge incontinence reported satisfaction with biofeedback, although women who were simply given verbal cues were even more satisfied (85%). A 2005 study of older women found that biofeedback worked better than oxybutynin (Ditropan) in controlling nighttime urge incontinence. Biofeedback that teaches control of pelvic muscles may even be very helpful in children who have daytime wetting, frequent urinary tract infections, or both.

A treatment called extracorporeal magnetic innervation therapy stimulates pelvic muscles to automatically perform Kegel exercises:

The patients stay fully dressed and sit on a special chair during the treatment.
Highly focused magnetic fields penetrate the pelvic area to stimulate the nerves.
Sessions are twice a week for about 6 weeks, although it may take more than 8 weeks to build up the muscles.

Studies report that patients experience fewer leaks, need fewer pads, and have fewer voiding episodes throughout the day and night. Comparison studies of magnetic therapy and sham (or "dummy") treatments are mixed, however, with some reporting no differences. More studies are needed to determine whether extracorporeal magnetic innervation therapy has any value.

Electrical stimulation of the pelvic floor muscles has been a common treatment for years. The procedure uses a probe inserted into the anus or vagina, which produces a contraction in the pelvic floor muscles. Success rates range from 50 - 90% for urge incontinence. (It may also be useful for some patients with stress incontinence.) A recent study regarding patient-adjusted intermittent electrostimulation in women with stress or mixed urinary incontinence using a new implanted stimulator found the concept promising. Researchers, however, encouraged further investigation regarding the effectiveness and safety of the technique. The procedure requires frequent visits, and it takes 2 - 3 months before the patient feels the benefits. It is often not covered by insurance. Side effects can be distressing and include abdominal cramps, diarrhea, bleeding, and infection.

Medications

A number of medications are available that increase sphincter or pelvic muscle strength or relax the bladder, improving the ability to hold more urine. Medications are prescribed for all kinds of incontinence, but they are generally most helpful for urge incontinence.

Anticholinergics. Anticholinergics work in the following ways:

Inhibit the involuntary contractions of the bladder
Increase capacity of the bladder
Delay the initial urge to void

A major 2003 analysis reported that these drugs produce small but significant improvements. However, the medications have not been rigorously compared with behavioral methods, such as bladder training and Kegel exercises, which are very effective for most cases of urge incontinence. Anticholinergics can have distressing side effects, notably dry mouth.

Anticholinergics include:

Propantheline (ProBanthine). This drug used to be the most commonly prescribed anticholinergic, but has been largely replaced by newer anticholinergics with fewer side effects.
Oxybutynin (Ditropan, Oxytrol)
Tolterodine (Detrol)
Hyoscyamine (Levbid, Cystospaz)

Extended-release versions of oxybutynin (Ditropan XL) and tolterodine (Detrol LA) are proving to be especially effective. They improve continence and have fewer adverse effects than short-acting forms. In a major 2003 comparison study of the extended release drugs, oxybutynin was slightly better than tolterodine, but dry mouth was reported more often. A skin patch form of oxybutynin (Oxytrol) is now available. It appears to work better and have fewer side effects, such as dry mouth and constipation, than the pill form.

Oxybutynin may cause more severe central nervous side effects than previously thought, especially for children and older adults. In 2007, the FDA reviewed 202 cases of oxybutynin-related central nervous system problems. Hallucinations were reported in 27% of pediatric cases and 25% of cases involving adults age 60 and older. Eleven percent of adults age 17 – 59 years experienced hallucinations. The FDA recommends that doctors monitor patients for these symptoms.

According to one study of tolterodine, the drug also improved quality of life. A 2006 study reported that tolterodine is helpful for men with overactive bladder and urge urinary incontinence. A 2006 study, published in the Journal of the American Medical Association, suggested that a combination of tolterodine and the alpha-blocker drug tamsulosin (Flomax) may work better than either drug alone for men with lower urinary tract symptoms, including overactive bladder.

Overactive Bladder Treatments for Children

Oxybutynin (Ditropan X) is approved for pediatric use in children ages 6 and older. The recommended dose is 5 mg once a day. A 2006 study suggested that children who have fewer episodes of daytime wetting may benefit most from this drug.
A 2004 analysis found that tolterodine is also effective and well tolerated in children with urinary symptoms due to overactive bladder.

Side effects of anticholinergic drugs include:

Dry eyes (a particular problem for people who wear contact lenses; patients who wear contacts may wish to start with low doses of medication and gradually build up)
Dry mouth
Headache
Constipation
Rapid heart rate
Confusion, forgetfulness, and possible worsening of mental function, particularly in older people with dementia, such as those with Alzheimer's disease
Hallucinations, possibly, especially for children and older adults
Glaucoma, in rare cases

Antispasmodics. Antispasmodic drugs help relax the bladder muscle and are used for urge incontinence. Before bladder relaxants are prescribed, a thorough evaluation for obstructions in the ureter must be performed to avoid excessive urine retention.

Flavoxate (Urispas) and dicyclomine (Bentyl), the most common antispasmodics, have been used for years, although studies suggest that Urispas has very little benefit for the majority of patients with urge incontinence. The drugs also have anticholinergic properties. In May 2004, the FDA approved a new antispasmodic, trospium chloride (Sanctura), for the treatment of overactive bladder with symptoms or urge incontinence.

Possible side effects reported with use of antispasmodic drugs include:

Weakness
Dizziness
Drowsiness
Hallucinations
Insomnia
Dry mouth
Impotence
Restlessness

M3 selective receptor antagonists. In 2004, the FDA approved darifenacin (Enablex) for treatment of urge incontinence and overactive bladder. Some clinical trials suggested that darifenacin could help reduce weekly incontinence episodes by 83%. The drug’s most common side effects are dry mouth and constipation. For elderly patients, darifenacin may have less negative effects on memory than oxybutynin.

Capsaicin and Analogs. Studies have reported beneficial effects from instillation of capsaicin, a component of hot red chili peppers, into the bladder of people with hyperactive and hypersensitive bladders. Temporary adverse effects, however, can be distressing. A capsaicin analog called resiniferatoxin may be more effective than capsaicin and have fewer side effects.

Alpha-Blockers. Alpha-blockers are drugs that relax smooth muscles and improve urine flow. They are useful for men with benign prostatic hyperplasia who also have urge incontinence. They include terazosin (Hytrin), doxazosin (Cardura), tamsulosin (Flomax), and alfuzosin (Xatral). Tamsulosin may be particularly beneficial. A 2006 study published in the Journal of the American Medical Association reported that the combination of tamsulosin and tolterodine works better than either drug alone for men with moderate-to-severe lower urinary tract symptoms, including overactive bladder. Men in the study were age 40 years and older and had symptoms related to overactive bladder and benign prostatic hyperplasia.

Alpha-Adrenergic Agonists. Alpha-adrenergic agonists are used to strengthen the smooth muscle that opens and closes the internal sphincter. They include ephedrine and pseudoephedrine, which are common ingredients in numerous over-the-counter decongestants and appetite suppressants.

Such drugs may be helpful for patients with mild stress incontinence not caused by nerve damage, although evidence on their benefits is weak. They also can have significant side effects, particularly ephedrine. In fact, products containing a similar drug, phenylpropanolamine (PPA), have been taken off the market because of reports of a higher risk for stroke in some women who took it.

Side effects may include agitation, insomnia, and anxiety. They may have adverse effects on the heart in people with existing heart problems. People with glaucoma, diabetes, hyperthyroidism, heart disease, or high blood pressure should avoid alpha-adrenergic agonists.

Nitrovasolidators. Deficiencies in nitric oxide, a gas that keeps blood vessels open, have been associated with many disorders, including incontinence. Drugs that release nitric oxide, such as nitroflurbiprofen, are being investigated for urinary incontinence.

Evidence indicates that both urge and stress incontinence are affected, in part, by central nervous system processes, particularly signal transmission. Investigators are particularly interested in serotonin and noradrenaline, which are chemical messengers (called neurotransmitters) that affect pathways involved with urination. (These neurotransmitters are also important for many other emotional and physical functions.) Antidepressants targeting one or both of these neurotransmitters are sometimes used for urge incontinence and may also be helpful for some people with stress incontinence.

Tricyclic Antidepressants. Tricyclic antidepressants include imipramine (Janimine, Tofranil), doxepin (Sinequan), desipramine (Norpramin), and nortriptyline (Pamelor). They provide multiple benefits for both urge and stress incontinence. They act as anticholinergic drugs and relax the bladder. They also strengthen the internal sphincter. These drugs should be used carefully. They pose some risk for adverse effects on the heart and possibly the lungs, and they have other severe side effects in older adults. These antidepressants produce side effects similar to anticholinergic drugs, and may cause drowsiness. They may also backfire and actually cause overflow incontinence in some people.
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs). SNRIs are specially designed antidepressants that are similar to tricyclics but do not have the same side effects. The neurotransmitters serotonin and norepinephrine are thought to play key roles in the normal action of bladder muscles and nerves. Increased neurotransmitter activity stimulates the nerve that controls the urethral sphincter. The SNRI duloxetine (Cymbalta) is approved in Europe for treatment of stress urinary incontinence. (It is approved in the U.S. for other conditions, but not stress urinary incontinence.) In 2005, the manufacturer of duloxetine withdrew its drug application after a small number of women in duloxetine urinary incontinence trials tried to commit suicide. The FDA is investigating whether duloxetine can cause suicidal behavior.

Desmopressin. Studies have reported that desmopressin (DDAVP), a drug used for bedwetting in children, may be helpful in treating adults with urinary incontinence that occurs during sleep. The drug affects sodium levels, and there is a slight risk for water intoxication with this drug.

Botulinum (Botox). Botulinum, the deadly toxin that sometimes contaminates improperly cooked foods, is also a powerful muscle-relaxant. Tiny injected amounts of a purified form (Botox) can relax the muscles and may help control overactive bladder that causes urge incontinence. It may also help relieve urinary retention that might occur after incontinence surgeries.

Stem Cells. Researchers are investigating muscle stem cell injections as a treatment for stress incontinence. Several small studies have indicated promising results. In these experiments, a doctor took a biopsy of skeletal muscle tissue from a patient’s arm. Stem cells were cultured and isolated from the biopsy sample. The doctor then injected the muscle-derived stem cells into the area surrounding the patient’s urethra that is close to the damaged sphincter muscle. In research results presented at the 2007 American Urological Association annual meeting and the 2006 Radiological Association of North American Meeting, patients experienced sustained improvements in bladder control and quality of life.

Surgery

There are nearly 200 procedures for incontinence. Most are designed to restore the bladder neck and urethra to their anatomically correct positions in patients with stress incontinence.

The American Urological Association suggests that surgery should actually be considered as initial therapy for women with severe stress incontinence. It is an effective and safe alternative when conservative treatments fail. Many of the procedures are safe even for women up to 80 years old who do not have serious medical conditions. Potential complications of all procedures include obstruction of the outlet from the bladder, causing difficulty in urination and irritation.

Deciding which procedure to choose is difficult and often depends on the factors causing the incontinence and whether anatomical abnormalities are involved. It should be noted that although hysterectomy has been shown to improve incontinence, it must not be performed only as a cure for incontinence.

In general, patients should weigh all options carefully. They should discuss the situation with their doctor, and ask about their surgeon's experience. As a general rule, the more times a surgeon has successfully performed a procedure, the better.

Retropubic Colposuspension Surgery. Retropubic colposuspension using standard "open" surgery is an effective treatment for stress incontinence, especially over the long term. ("Open" surgery implies the use of a wide incision in order to "open" the area.) Long-term continence rates can range from 85 - 90%.

The goal of colposuspension is to correct the position of the bladder and urethra by sewing the bladder neck and urethra directly to the surrounding pelvic bone or nearby structures. There are many variants, but, in general, they are effective only for women with urethral hypermobility. Most procedures require a general or spinal anesthetic and a 2-day hospital stay.

Burch colposuspension (sometimes called colpocystourethropexy) is a standard approach. It requires a wide abdominal incision and is often performed during abdominal surgeries such as hysterectomy or hernia operations. It is also performed along with sacrocolpopexy, a surgical procedure used to repair pelvic organ prolapse. (Pelvic organ prolapse occurs when the uterus or bladder slips from the pelvic cavity into the vagina. It is often due to pelvic muscle weakness that develops after childbirth.) Prolapse can lead to stress incontinence. However, prolapse surgery itself sometimes causes incontinence. A 2006 study suggested that a Burch colposuspension performed at the same time as sacrolpopexy can help reduce postsurgical stress incontinence.

The surgeon secures the urethra and bladder neck with lateral (sideways) sutures that pass through thick bands of muscle tissue running along the pubic bones. Unlike an older suspension procedure, this procedure poses a much lower risk for obstruction of the urethra. It is more effective in premenopausal than postmenopausal women and may not be appropriate for all women.

A rigorous 2007 study published in the New England Journal of Medicine compared the effectiveness of the Burch colposuspension to the sling procedure, another type of surgical treatment for stress incontinence. The study found that the sling procedure had better results for achieving dryness. However, more women who had the sling procedure had post-operative urinary problems, especially urinary tract infections. Overall, women were satisfied with the outcomes of both procedures. Eighty-six percent of women who had a sling procedure and 78% of women who had a Burch colposuspension reported satisfaction with their treatment.

Marshall-Marchetti-Krantz (MMK). The MMK approach requires a wide abdominal incision. The surgeon then elevates the urethra and bladder neck using sutures. These structures are then secured and anchored in nearby cartilage. This approach is one of the most reliable, but is used less often because of the risk for scarring and because the incision limits the surgeon's ability to correct any potential hernias (cystoceles).

Click the icon to see an illustrated series detailing bladder neck surgery.

Laparoscopy. Other less invasive procedures use laparoscopy, which requires only one or two small incisions over the pubic bone. Evidence suggests that laparoscopy, performed by an experienced surgeon, works just as well as standard surgery. While laparoscopy has a higher complication rate, it also has a faster recovery time and less postoperative pain. Still, well-conducted long-term studies are needed for an accurate comparison with standard colposuspension.

Needle Suspension. Needle suspensions include a number of approaches, including the Pereyra, Stamey, Raz, and Gittes procedures. The basic approach places stitches on either side of the bladder and ties them to muscle tissue or the pubic bone. Some of these procedures use transvaginal suspension, which requires only a small abdominal incision or no incision at all. In this case, the surgeon works through the vagina and places sutures through the vaginal walls. Transvaginal suspension works only if the walls of the vagina are strong enough to withstand the procedure. Some studies report poor long-term results, particularly compared to colposuspension. In one study, only 35% of patients who had transvaginal suspension reported success after 6 years. In another study, the failure rate was 83% after 4 - 5 years. Additional research has indicated that 20% of women have worse sexual function after the procedure.

Postoperative Considerations for Most Procedures. Following most standard procedures, patients usually leave the hospital on the second or third day, but need a urinary catheter for about 10 days. Newer procedures may require shorter stays and less intensive postoperative care.

Complications after surgery include:

Some risk of damage to the surrounding nerves or vessel. This can result in internal sphincter deficiency. (In some cases it may already have been present before the operation.)
Difficulty in urinating from surgical overcorrection. (This may require additional surgery.)
Poor wound healing.
Adhesions (scar tissue) that obstruct the urethra. This complication is higher with older standard procedures.
Vaginal abnormalities (prolapsed vagina).

A sling procedure may be a good option for severe stress incontinence in women who have either intrinsic sphincter deficiency or urethral hypermobility. The method is even proving to help women with mild-to-moderate incontinence and young girls with severe incontinence. It may also be useful for managing female urge incontinence. Sling procedures are also available for men who experience incontinence after prostatectomy.

Until recently, there were few clinical trials that directly compared the sling procedure with Burch colposuspension. In 2007, the New England Journal of Medicine published the results of the largest and most rigorous clinical trial conducted on these two types of surgery. In this study of 655 women with stress incontinence, half of the women underwent the sling procedure and half had open surgery with the Burch colposuspension.

Two years after surgery, success rates were highest for women who had the sling procedure. Forty-seven percent of women who had the sling procedure reported no urinary incontinence (either stress or urge) compared to 38% of women who had the Burch procedure. For stress-only incontinence, 66% of women who had the sling procedure and 49% of women who had the Burch procedure were dry. Eighty-six percent of women who had the sling procedure and 78% of the Burch group reported satisfaction with their treatment.

However, women who had the sling procedure did experience more post-operative urinary problems. The most common complication was urinary tract infections, which affected 63% of women who had a sling procedure compared with 47% of women who had the Burch procedure. A small number of women who had a sling procedure also reported difficulty voiding and urge incontinence.

The Percutaneous Sling Procedure for Women. The procedure generally works as follows:

The surgeon makes an incision above the pubic bone and removes a layer of abdominal fasci (tissue that covers muscle fibers). This muscle strip is set aside and later serves as the sling. (The uses of fasci taken from a cadaver or synthetic slings are also being investigated. However, the natural muscle strip may last longer than some of the common synthetic materials.)
The surgeon makes an incision in the vaginal wall. The piece of muscle fiber or material is attached under the urethra and bladder neck, somewhat like a hammock, and secured to the abdominal wall and pelvic bone.
This sling then compresses the urethra back to its original position. The sling must be supportive without being too tense, which can cause urinary obstruction.

Complications can include infection, bleeding, and the formation of fistulas (holes that form and are usually infected).

Vaginal Sling and Tape Procedures for Women. Newer outpatient procedures do not use abdominal incisions. Instead, they are performed through a small incision in the vagina. Typically, two small tacks are placed in the pubic bone. A sling is inserted into the vagina and is attached to the tack.

The tension-free vaginal tape (TVT) procedure uses a special gauze tape covered by a polypropylene coating, which is attached on each side of the urethra. The patient remains conscious and is asked to cough during the procedure so that the surgeon can determine if the tape is secure. Small early studies showed that the procedure worked as well as colposuspension (the standard suspension procedure), with stress incontinence cure rates of 84 - 100%. According to a 2005 study, the benefits of TVT can last for up to 8 years for women with stress incontinence. However, women with mixed incontinence (a combination of stress and urge) did not fare as well. Women with mixed incontinence had a 60% cure rate during the first 4 years following surgery, but the cure rate declined to 30% within 4 - 8 years post-surgery.

Sling Procedures in Men. For some men who have prostatectomy-induced incontinence, sling procedures may be a good option. Researchers have reported an 80% success rate, the same as an artificial urinary sphincter, which is the standard surgical treatment for such patients. The sling procedure has been less effective in men who have had radiation therapy, although improved techniques are making this approach useful even for these patients. Minimally invasive procedures are also being tested.

Artificial Sphincter. In cases of sphincter incompetence, or complete lack of sphincter function, an artificial internal sphincter may be implanted. This procedure is useful for appropriate male and female candidates of any age, including children. It is particularly helpful for men after radical prostatectomy. Studies have found poor results for patients with incontinence due to radiation therapies, although a 2001 study of men with prostatectomy indicated that it was useful regardless of previous radiation therapy.

Click the icon to see an illustrated series detailing artificial sphincter surgery.

This device uses a balloon reservoir and a cuff around the urethra that is controlled with a pump. The patient opens the cuff manually by activating the pump. The urethra opens and the bladder empties. The cuff closes automatically several minutes later. The two major drawbacks of the internal sphincter implant are:

Malfunction. If the implant malfunctions, the surgery must be performed again.
Infection. Infection is more serious as it can cause erosion of the urethra or bladder neck underneath the implant. Such infections not only require removal of the device, but also may worsen the incontinence. Fortunately, techniques have improved so that infection is uncommon.

In a 2001 study, after an average of 7 years, 70% of female patients with stress incontinence had either the original implant or a replacement, and 82% had urination properly restored. (Only 37% still had the original implant, however.) Studies on men have reported similar findings, although newer devices that use narrow cuffs may significantly improve re-implantation rates. Nearly all patients still need to use pads for leakage.

Injections of materials, such as collagen, that provide bulk to help support the urethra are proving to be beneficial for the following patients:

Women (even the elderly) with severe stress incontinence who cannot or do not wish to have surgery that involves anesthesia.
Men who have slight incontinence caused by prostate surgery. Men who have bulking injections after TURP (transurethral resection of the prostate) have a continence rate that is equal to the rate in women. After radical prostatectomy (removal of the prostate gland in prostate cancer), collagen injections can achieve some level of continence in up to nearly half of men. (Collagen injections are not beneficial after radiation therapy for prostate cancer.)

The Procedure.

First, bladder instability or hyperactivity should be medically treated and managed to control muscle activity before having the procedure. Otherwise it is likely to fail.
The basic procedure involves injecting bulking material into the tissue surrounding the urethra.
The material used is usually animal or human collagen. (Collagen is the basic protein in bones, muscles, and all connective tissue.) Synthetic bulking materials, such as carbon-coated beads, are also being used.
The doctor passes the collagen-containing needle through a cystoscope, a tube that has been inserted into the urethra. The collagen can also be injected into the skin next to the sphincter.
The injected collagen tightens the seal of the sphincter by adding bulk to the surrounding tissue.
The procedure takes about 20 - 40 minutes, and most people can go home immediately afterward.
Two or three additional injections may be needed to achieve satisfactory results.

Postoperative Care. People may experience immediate improvement followed by a temporary relapse after a week or so. Patients must be taught to use a catheter tube for withdrawing urine for a few days following the procedure. In general, it takes about a month for the full benefits to be apparent.

Complications.

There is a risk for infection and urinary retention, although these conditions are temporary.
An increase in autoimmune disease has been reported in a small number of cases.
The procedure may not be appropriate for patients with certain cardiac conditions.

Duration of Effectiveness. Collagen is absorbed over time, so injections generally need to be repeated every 6 - 18 months. According to one study, however, after a year 44% of women who had the implants still experienced the same level of improvement. (Synthetic materials may last longer than collagen from other sources, but they pose a risk for rejection as well as migration to the lymph nodes and other parts of the body.)

Anterior vaginal repair procedures that correct a prolapsed (fallen) uterus or vagina can often correct incontinence in women who have these conditions. The anterior vaginal repair (also called a bladder tuck) requires an incision to be made through the vagina. This releases part of the anterior (front) vaginal wall, which is attached to the base of the bladder. The pubocervical fascia (the supportive tissue between the vagina and bladder) is folded and stitched to bring the bladder and urethra into proper position. Several variations on this procedure may be necessary, depending on the severity of the prolapse. It is not as effective as retropubic suspension procedures, however, and should not be used as the primary method for correcting incontinence.

An interesting investigative approach uses radiofrequency energy to shrink tissue that supports the bladder neck and reduces hypermobility. Early studies are promising. In one, for example, the cure rate was nearly 80% at the end of a year, and 83% of patients reported satisfaction with the procedure.

Other Procedures

The sacral nerves, located in the tail bone, appear to play an important role in regulating bladder control. A sacral nerve stimulation system (InterStim) is now available for patients with urge incontinence. The system sends electrical pulses to the sacral nerves to help retrain them. InterStim is reserved for the treatment of urinary retention and the symptoms of overactive bladder in patients who have failed or cannot tolerate less invasive treatments. The system works as follows:

A stopwatch-size device is implanted under the skin in the abdomen.
A wire connected to it runs to the sacral nerves in the lower back.
The device, a battery-operated generator, produces electrical pulses.
The pulses are sent to the sacral nerves and reduce the hyperactivity of the bladder.
The sensation of the electrical pulse is similar to a slight pulling sensation in the pelvic area. Sometimes it can cause a small jolt or shock if the patient changes posture quickly. It should not cause pain. (If it does, something is wrong with the device.)

Complications include infection, lower back pain, and pain at the implant site. The system, however, does not cause nerve damage and can be removed at any time.

Patients have reported improvement in the frequency and volume of urination, as well as the intensity of urgency and their quality of life. Studies report complete dryness in nearly half of patients, with about 75% of patients experiencing relief from heavy leaking.

Transcutaneous Neuromodulation. The use of electrodes on the surface of the skin, called transcutaneous neuromodulation, may prove to be beneficial and particularly attractive for children.

Percutaneous Stoller Afferent Nerve Stimulation. The percutaneous stoller afferent nerve system (PerQ SANS System) has also been approved for urge incontinence.

In this therapy, a very thin needle is inserted a short distance above the ankle bone.
The needle is applied to the tibial nerve in the ankle, which connects with the sacral nerve complex.
Low-frequency electrical stimulation is applied for 30 minutes once a week for about 3 months.
After that, depending on the patient's response, treatments are given every week to every other week.
Short-term results are promising, but more research is needed.

Catheters and Collection Devices

A catheter is a slim flexible tube inserted into the urethra. They are mainly used for cases of severe urge incontinence.

A catheter (a hollow tube) may be inserted into the urinary bladder when there is a urinary obstruction, following surgical procedures to the urethra, in unconscious patients (due to surgical anesthesia, coma, etc.), or for any other problem in which the bladder needs to be kept empty (decompressed) and urinary flow assured.

Click the icon to see an image of male bladder catheterization.

Temporary Catheterization. For people who are still active, catheterization is often very distressing. If possible, temporary, also called intermittent, catheterization is usually the best choice. Patients insert the catheter tube into their urethras, generally every 3 - 4 hours. This type of catheterization carries few risks and empties the bladder completely. Some patients report that they can maintain an active life with no significantly increased risk for infection with some simple precautions:

Sterilize catheters at home.
Use a Zip Lock plastic bag for carrying them when leaving home.
Use another plastic bag for antiseptic cleansing solution.
When using public bathrooms, wash before and after catheterization. Touch as few places in the bathroom as possible.

Permanent Catheterization. People who are mentally or physically incapable of self-catheterization may need permanent catheterization.

The permanent catheter is inserted by a doctor or nurse into the opening of the bladder and a cuff is inflated to hold the tube in place.
Urine drains to an external collection device, which is generally strapped to the leg and must be emptied periodically.

The procedure is not painful, but there is a substantial increased risk of infection. Many experts feel that the catheter is overused, especially in the elderly.

Condom Catheters. Condom catheters are much more satisfactory than standard catheters for many male patients, although there is more spillage.

The condom is worn all day.
At night it is removed and washed for reuse the next day.

Collection Devices Attached to the Leg. For chronic or severe incontinence, collective devices drain urine into a bag that is attached to the lower leg and emptied periodically. These are generally more successful for men. Urine can be funneled into the tube by a pouch surrounding the penis. The positioning of the collecting device is difficult for women, and more accidents occur. For both men and women, irritation of the area around the urethral opening is a problem, since urine is in contact with the area for long periods.

Resources

www.nafc.org -- National Association for Continence
www.simonfoundation.org -- The Simon Foundation for Continence
www.niddk.nih.gov -- National Kidney and Urologic Diseases Information
www.acog.org -- American College of Obstetricians and Gynecologists
www.augs.org -- American Urogynecologic Society
www.kegel-exercises.com -- Information on Kegel Exercises
www.urologyhealthy.org -- Urology Health from the American Urological Association

References

Albo ME, Richter HE, Brubaker L, et al. Burch colposuspension versus fascial sling to reduce urinary stress incontinence. N Engl J Med. 2007 May 24;356(21):2143-2155. Epub 2007 May 21.

Harris SS, Link CL, Tennstedt SL, Kusek JW, McKinlay JB. Care seeking and treatment for urinary incontinence in a diverse population. J Urol. 2007 Feb;177(2):680-4.

Kaplan SA, Roehrborn CG, Rovner ES, Carlsson M, Bavendam T, Guan Z. Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. JAMA. 2006 Nov 15;296(19):2319-28.

Litwin MS, Saigal CS, editors. Urologic Diseases in America. US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, DC: US Government Printing Office, 2007; NIH Publication No. 07–5512.

Review Date:
6/15/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Headaches - cluster

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

In This Report

Highlights
Introduction
Cluster Headaches
Causes
Prognosis
Risk Factors
Diagnosis
Managing Cluster Headaches...
Treatment for Acute Attacks...
Preventive Medications
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Verapamil May Cause Heart Problems

Verapamil (Calan) is a blood pressure medication that is used "off-label" as a first-line preventive treatment for cluster headaches. However, when used for cluster headache, this drug may sometimes cause dangerous disturbances in heart rhythms (arrhythmia), according to a 2007 study in Neurology. The researchers recommend that patients who take verapamil should receive regular electrocardiograms to monitor for any signs of potential heart problems.

Zolmitriptan for Cluster Headache Treatment

Zolmitriptan (Zomig) nasal spray is a safe and effective treatment for cluster headache pain, indicates a 2007 study in Neurology. Because cluster headache pain can quickly become excruciating, researchers would like to find a treatment that can provide rapid pain relief. In a small study, patients who administered either 5 mg or 10 mg of zolmitriptan during a cluster headache attack received relief within 30 minutes. For some patients, the higher dose took effect within 10 minutes. Zolmitriptan is a triptan drug that is commonly used to treat migraine headaches.

Occipital Nerve Stimulation

Occipital nerve stimulation may be a safer alternative to deep brain (hypothalamus) stimulation. Both investigational neurostimulation techniques involve surgically implanting a wire in the brain. The wire is then attached to a small pacemaker-like device. Neurostimulation is used only for patients with intractable cluster headaches who have not responded to drug therapy. In studies published in 2007 in Lancet and Lancet Neurology, several patients who received occipital nerve stimulation became pain-free or had a reduction in the frequency of their cluster headache attacks.

Introduction

Most people have had headaches. There are many different kinds of headaches, and they range from being an infrequent annoyance to a persistent, severe, and disabling medical condition.

The brain is insensitive to pain, so that is not what hurts when you have a headache. Rather, the pain occurs in the following locations:

The tissues covering the brain
The attaching structures at the base of the brain
Muscles and blood vessels around the scalp, face, and neck

Doctors categorize headaches as either primary or secondary. The category helps to distinguish the many different kinds of headaches and to determine right treatments for each.

A headache is considered primary when a disease or other medical condition does not cause it. Most primary headaches fall into three main types: tension-type, migraine, and cluster headaches.

Tension headache is the most common primary headache and accounts for 90% of all headaches.
Migraines are the second most frequently occurring primary headaches. Migraine is referred to as a neurovascular headache because it is most likely caused by an interaction between blood vessel and nerve abnormalities.
Cluster headache is a less common type of primary headache. Although it is sometimes referred to as a neurovascular headache, evidence now suggests that its cause lies in the hypothalamus, a region deep in the brain that regulates, among other functions, the biologic rhythms of the body.

Headaches are usually caused by muscle tension, vascular problems, or both. Migraines are vascular in origin, and may be preceded by visual disturbances, loss of peripheral vision, and fatigue. Most headaches can be relieved by over-the-counter pain medications.

Secondary headaches are caused by other medical conditions, such as sinus infections, neck injuries, and strokes. About 2% of headaches are secondary to abnormalities or infections in the nasal or sinus passages, and they are commonly referred to as sinus headaches.

The International Headache Society has developed a classification system that includes a category called chronic daily headaches. They may originate as tension headaches, migraines, or a combination of these or other headache types. Chronic daily headaches affect 4 - 5% of the population.

Chronic daily headaches are defined as any benign headache that occurs at least 15 days a month and is not associated with a serious neurologic abnormality. Most people with these headaches have them daily or almost daily and they can be quite debilitating.

Chronic daily headaches are, in turn, subdivided into two categories:

Short-duration headaches, or those lasting fewer than 4 hours. The most common short-acting chronic headaches are cluster headaches.
Long-duration headaches, which last more than 4 hours. Tension-type headaches are the most common type of long-duration chronic (recurring) headaches and, in fact, the most common type of chronic headaches in general.

Click the icon to see an image of the different types of headache.

Cluster Headaches

Cluster headaches are among the most painful, and least common, of all headaches. The pain can be so excruciating that they are sometimes referred to as “suicide headaches." Their signature is a pattern of periodic cycles (“clusters”) of headache attacks, which may be either:

Episodic. Attacks occur regularly for 1 week to 1 year, separated by long pain-free periods that last at least 1 month. Between 80 – 90% of patients have episodic cycles. A significant percentage of people who experience a first cluster attack do not have another one.
Chronic. Attacks occur regularly for more than 1 year, with pain-free periods lasting less than 1 month. Between 10 – 20% of patients have chronic cluster headaches. The chronic form is very difficult to treat.

Cluster headaches usually strike suddenly and without warning, although some people experience a migraine-type aura before the attack. A stabbing pain quickly develops behind one eye or on the temple of one side of the head. The pain then spreads to the forehead, jaw, upper teeth, or neck. The pain and other symptoms usually remain on one side of the head.

Other typical symptoms include:

Swollen or droopy eyelid
Watery, tearing eye
Contraction of the eye pupil
Stuffy or runny nose
Forehead and facial sweating
Restlessness and agitation
Nausea and vomiting
Intolerance to light and sound

The symptoms of a cluster headache include stabbing severe pain behind or above one eye or in the temple. Tearing of the eye, congestion in the associated nostril, and pupil changes and eyelid drooping may also occur.

Typical Cluster Cycles

Timing of an Attack. Headache attacks tend to occur with great regularity at the same time of day. (For this reason, cluster headaches are sometimes referred to as “alarm clock” headaches.) About 75% of attacks occur between 9 p.m. - 10 a.m. Attacks may also peak between 1 - 3 p.m.

Duration of an Attack. A single cluster attack is usually brief but extremely painful, lasting about 15 minutes – 1.5 hours if left untreated.

Number of Attacks per Day. During an active cycle, people can experience as few as 1 attack every other day to as many as 8 attacks a day.

Duration of a Cycle. Attack cycles typically occur seasonally -- most often in spring and autumn. Usually a patient has one or two cycles per year that each last 1 - 3 months.

Headache-Free Remissions Between Cycles. Such cycles are followed by headache-free periods lasting at least several weeks, and often for many months. Sustained remissions can last for 20 years.

Migraine Headache: General Description of Its Course

Migraine is now recognized as a chronic illness, not simply as a headache. Migraines are often classified by whether they are accompanied by auras:

Common migraines are without auras; about 75% of migraines are the common type.
Classic migraines are those with auras.

A person may experience one or the other at different times. In general, there are four symptom phases to a migraine (although they may not all occur in every patient): the prodrome, auras, the attack, and the postdrome phase.

Prodrome. The prodrome phase is a group of vague symptoms that may precede a migraine attack by several hours, or even a day or two. Such prodrome symptoms can include:

Sensitivity to light or sound
Changes in appetite
Fatigue and yawning
Malaise
Mood changes
Food cravings

Auras. Auras are sensory disturbances that occur before the migraine attack in 20 - 25% of patients. Visually, auras are referred to as being positive or negative:

Positive auras include bright or shimmering light or shapes at the edge of their field of vision called scintillating scotoma. They can enlarge and fill the line of vision. Other positive aura experiences are zigzag lines or stars.
Negative auras are dark holes, blind spots, or tunnel vision (inability to see to the side).

Patients may have mixed positive and negative auras. This is a visual experience that is sometimes described as a fortress with sharp angles around a dark center.

Other neurologic symptoms may occur at the same time as the aura, although they are less common. They include:

Speech disturbances
Tingling, numbness, or weakness in an arm or leg
Perceptual disturbances such as space or size distortions
Confusion

Migraine Attack. If untreated, attacks usually last from 4 - 72 hours. A typical migraine attack produces the following symptoms:

Throbbing pain on one side of the head. The word migraine, in fact, is derived from the Greek word hemikrania, meaning "half of the head" because the pain of migraine often occurs on one side. Pain also sometimes spreads to affect the entire head.
Pain worsened by physical activity
Nausea, sometimes with vomiting
Visual symptoms
Facial tingling or numbness
Extreme sensitivity to light and noise
Looking pale and feeling cold

Less common symptoms include tearing and redness in one eye, swelling of the eyelid, and nasal congestion, including runny nose. (Such symptoms are more common in certain other headaches, notably cluster headaches. In one study, however, they occurred in over 40% of migraine sufferers.)

Postdrome. After a migraine attack, there is usually a postdrome phase, in which patients may feel exhausted and mentally foggy for a while.

Tension-Type Headache

Tension-type headaches, also called muscle contraction headaches or simply tension headaches, are the most common of all headaches. Tension-type headaches can last minutes to days and may have the following characteristics:

The pain is commonly described as a tight feeling, as if the head were in a vise. It usually occurs on both sides of the head and is often experienced in the forehead, in the back of the head and neck, or in both regions. Soreness in the shoulders or neck is common.
Depression, anxiety, and sleeping problems may accompany persistent headaches.

People who suffer from tension-type headaches may also have migraine-like symptoms, including being sensitive to light or noise (but not both). Some patients also may suffer from visual disturbances. (Such symptoms in tension headaches, however, tend to be less severe than in migraine. Tension headaches also do not cause nausea or limit activities to the degree that migraines do.)

Other Primary Headaches

Chronic Paroxysmal Hemicrania. Chronic paroxysmal hemicrania is a close relative of cluster headache and very similar. It causes multiple, short, and severe daily headaches with similar symptoms. Unlike cluster headaches, the attacks are shorter (1 - 2 minutes) and more frequent (occurring an average of 15 times a day). This headache is even rarer than cluster headache, tends to occur in women, and always responds to treatment with indomethacin.

Hemicrania Continua. Hemicrania continua occurs mostly in women. The patient generally experiences continuous low-level headache always on one side of the face. Periodic attacks can last days to weeks, which can be mild to severe, and may resemble migraines. (About 10% of patients experience remissions.) The headaches can usually be treated successfully with indomethacin, which helps differentiate if from other headaches, notably migraines.

SUNCT Syndrome. A disorder called SUNCT syndrome (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) causes stabbing or burning eye pain that may resemble cluster headaches, but attacks are very brief (lasting about a minute) and may occur more than 100 times per day. Red and watery eyes, sweating forehead, and congestion are typical. This rare headache is more common in men and does not respond to other headache treatments.

Causes

Cluster headaches, like migraines, are likely due to an interaction of abnormalities in the blood vessels and nerves that affect regions in the face.

Evidence strongly suggests that abnormalities in the hypothalamus, a complex structure located deep in the brain, may play a major role in cluster headaches. Advanced imaging techniques have shown that a specific area in the hypothalamus is asymmetrical in these patients and is activated during a cluster headache attack.

The hypothalamus is involved in the regulation of many important chemicals and nerve pathways, including:

Click the icon to see an image of the hypothalamus.

Nerve clusters that regulate the body's biologic rhythms (its circadian rhythms)
Serotonin and norepinephrine. These are neurotransmitters (chemical messengers in the brain) that are involved with well-and appetite.
Cortisol (stress hormones)
Melatonin (a hormone related to the body's response to light and dark)
Beta-endorphins (substances that modulate pain)

Circadian Abnormalities. Cluster attacks often occur during specific sleep stages. They also often follow the seasonal increase in warmth and light, beginning in summer and ending in the fall. Researchers have therefore focused attention on circadian rhythms, and in particular small clusters of nerves in the hypothalamus that act like biologic clocks.

The most important nervous cluster is the suprachiasmatic nuclei (SCN), which appears to help coordinate the body's activities (sleep/wake) with the environment (dark/light). Some studies support the idea that some failure in this biologic pacemaker may impair the pain control system and cause these terrible attacks.

The hormone melatonin is also involved in the body's biologic rhythms.

Alterations in Serotonin. The brain chemical serotonin is of particular interest in the study of headaches, particularly migraine and cluster headaches. This neurotransmitter (chemical messenger) affects, among other functions, well-being, sleep, and appetite. Some research has also suggested that serotonin may play an important role in the way circadian rhythms are expressed. There is some evidence of abnormal regulation of brain serotonin levels in patients with cluster headaches (although it is not as pronounced as in patients with migraine).

Cluster headaches are associated with dilation (widening) of blood vessels and inflammation of nerves behind the eye.

Cluster headaches may be caused by blood vessel dilation in the eye area. Inflammation of nearby nerves may give rise to the distinctive stabbing, throbbing pain usually felt in one eye. The trigeminal nerves branch off the brainstem behind the eyes and send impulses throughout the cranium and face.

In both cluster and migraine headaches blood vessels dilate, but in cluster headaches only the blood vessels behind the eyes pulsate. What causes these events and how they relate to cluster headaches are still unclear:

Because blood vessel dilation appears to follow, not precede, the pain, some action originating in the brain is likely to be part of the primary process.
Some experts believe that at least some of the pain is caused by dilation in branches of the carotid artery (a major artery that supplies the brain with blood).
Certain substances, such as histamine and a protein called endothelin-1 that widens blood vessels and are being investigated for a possible role in cluster headaches.

Nitric Oxide. Nitric oxide is a small molecular messenger that activates nerve pathways in the brain, muscles, or elsewhere. It may contribute to major primary headaches (tension-type, cluster, and migraines) by specifically triggering inflammation and overactivity in the trigeminal nerves. (This is a major nerve pathway that runs from the brain stem to the head and face.) However, other factors must be present that make patients with cluster headaches susceptible to the actions of nitric oxide.

Immune Abnormalities. Researchers are also investigating whether overproduction of certain immune factors called cytokines may contribute to cluster headaches. Cytokines, such as interleukins, are known to cause inflammation and injury in high amounts. To date, however, there is no evidence that they play any role.

Abnormalities in the Sympathetic Nervous System. Some evidence suggests that abnormalities in the sympathetic (also called autonomic) nervous system may contribute to cluster headaches. This system regulates non-voluntary muscle actions in the body, such as in the heart and blood vessels.

About 90% of people seeking help for headaches have a primary headache. The rest have secondary headaches, caused by an underlying disorder that produces headache as a symptom. More than 300 conditions can cause headaches. Some of the most common are listed below.

Sinus Headaches. Many primary headaches, including migraines, are misdiagnosed as sinus headaches. Sinus headaches can occur in the front of the face, usually around the eyes, across the cheeks, or over the forehead. They are usually mild in the morning and increase during the day and are usually accompanied by fever, runny nose, congestion, and general debilitation. Sinus headaches spread over a larger area of the head than migraines, but it is often difficult to tell them apart, particularly if headache is the only symptom of sinusitis. Both types of headache even coexist in many cases. Often, the visual changes associated with migraine can rule out sinusitis, but such visual changes do not occur with all migraines. (In rare cases, sinusitis can cause double vision and even vision loss, a sign of very serious infection.)

Headaches that Originate in the Neck. Some headaches may be caused by abnormalities of the neck muscles (called cervicogenic headaches). Nerves in the neck converge in the trigeminal nerve, which is the largest nerve in the skull. It originates in the brain stem and supplies sensation to the face. This nerve can generate pain signals to the facial area that the brain may interpret as headache. Pain is usually on one side. Even if pain affects both sides of the head, it is usually more severe on one side. The quality of the headache may be difficult to distinguish from an aching tension headache or a mild migraine without aura. Cervicogenic headaches can result from prolonged poor posture (such as that caused by sitting in front of a computer keyboard or driving daily for long periods), arthritis, injuries of the upper spine, or abnormalities in the cervical spine (the spinal bones in the neck).

Temporomandibular Joint Disorder. Muscle contractions that cause headaches may be a result of temporomandibular joint dysfunction (TMJ, also called TMD), which is caused by clenching the jaws or grinding the teeth (usually during sleep), or by abnormalities in the jaw joints themselves. The diagnosis is easy if chewing produces pain or if jaw motion is restricted or noisy. TMJ pain can occur in the ear, cheek, temples, neck, or shoulders. This condition often coexists with chronic tension headache.

Glaucoma. Acute glaucoma is caused by increased pressure in the eye and requires immediate medical attention. Throbbing pain may be felt around or behind the eyes or in the forehead. Patients have redness in the eye and may see halos or rings around lights.

Click the icon to see a depiction of glaucoma.

Click the icon to see an image of the slitlamp test.

Click the icon to see an image of the visual field test.

Brain Tumor. Fear of brain tumor is common among people with headaches, but headache is almost never the first or only sign of a tumor. Changes in personality and mental functioning, vomiting, seizures, and other symptoms are more likely to appear first. When the headache does develop, it is often worse early in the morning or may awaken sufferers during the night.

Neuralgia. Neuralgia is pain due to nerve abnormalities, which can occur in the facial area and resemble migraines or sinus headaches.

Hypertension. Although many people attribute headaches to high blood pressure, the weight of evidence suggests that hypertension does not cause head aches. An exception is malignant hypertension, an uncommon medical emergency in which the blood pressure abruptly rises to extreme levels, causing damage to blood vessels in the brain, heart, and kidneys.

Strokes Caused by Blood Clots or Hemorrhages. A blood clot or hemorrhage in the brain leading to a stroke can cause a severe headache, sometimes referred to as a thunderclap headache when it is very sudden and severe. The onset of such a headache, particularly if it is associated with confusion, stupor, or other neurologic symptoms, mandates prompt medical attention.

Epilepsy. Severe headaches that can last 12 hours or longer are very common in epilepsy. Migraine is particularly associated with epilepsy.

Head Injuries. It is obvious that a significant blow to the head will cause pain. In most cases, the pain is similar to tension-type headache and is treated in the same way as the primary headache. Post-injury headaches, however, can reflect serious damage, ranging from skull fractures to internal bleeding, and monitoring is important.

Disorders of the Meninges. The meninges are the membranes covering the brain and the spinal cord. Meningitis, which is an infection or irritation of these membranes, is an uncommon but potentially serious cause of severe headache. Other symptoms include nausea and stiffness or pain in the neck.

Gynecologic Problems. Many clinicians have anecdotally linked gynecologic problems, such as ovarian cysts and menstrual disorders, to chronic headaches, and new data are emerging to support this association.

Temporal (Giant Cell) Arteritis. Certain causes of headaches are unique to the elderly, such as temporal arteritis, also called giant cell arteritis. Inflammation in arteries that carry blood to the head, neck, and sometimes the upper part of the body can cause very severe headaches. The risk for this headache is highest in people over age 70, especially among women, people of European heritage, and patients with polymyalgia rheumatica.

Miscellaneous Causes of Benign Headaches. Rapid consumption of ice cream or other very cold foods or beverages is the most common trigger of sudden headache pain, which may be prevented by warming the food or drink for a few seconds in the front of the mouth before swallowing. Other common benign causes of headache include eyestrain, dental problems, allergies, systemic infections, and caffeine withdrawal. Headaches may be induced by sexual activity or intense physical exertion. Leakage from spinal cord fluid is rare but can cause headaches that may be mistaken for brain tumors.

Prognosis

The pain of cluster headaches can be intolerable. In fact, a higher-than-average rate of suicide has been reported in men with these headaches. Eventually, the attacks cease, but experts cannot predict when or how they will end.

People with episodic cluster headaches tend to have low sexual appetites and impaired verbal memory and are more likely to suffer from anxiety. According to one study, nearly a quarter of patients with cluster headaches met the criteria for having anxiety disorders. Furthermore, the anxiety disorders occurred more frequently within the year before the onset of their cluster headaches. (None of these patients had depression or abused alcohol or drugs.) Some studies suggest that the biologic abnormalities in the hypothalamus of the brain that are associated with episodic cluster headaches may also contribute to these emotional and mental difficulties.

In rare cases, patients with cluster headaches have migraine-like aura. Headaches that are accompanied by aura may increase the risk of stroke or transient ischemic attack (TIA). A 2005 study found that patients who had headaches with auras were about four times more likely to have a stroke or TIA than patients who had headaches without aura. TIA symptoms are similar to those of stroke, but last only briefly. A TIA is often a warning sign that a person is at risk for a more severe stroke.

Headaches with auras may also increase the risk for eye retinal damage (retinopathy), which can lead to severe vision problems or blindness. The risks for stroke and retinopathy are associated with the effects of aura-related headaches on small blood vessels in the brain and the eyes.

Risk Factors

Cluster headaches are rare, affecting less than 1% of the population.

Cluster Headaches in Men. Cluster headaches are much more common in men than in women, about 85% of cluster headache sufferers are men. The peak age of onset for men is the 20s to early 30s.

Cluster Headaches in Women. Studies of cluster headaches in women report that there are two ages of peak onset, the 20s and 50s. In some studies, attacks in women were of shorter duration than in men, but the duration of the episodes and length of remission were similar. Unlike with migraines, fluctuations in estrogen and other female hormones do not appear to influence the onset of attacks, although attacks may be less frequent during pregnancy.

Cluster headaches typically start in the late twenties. In rare cases they begin in childhood, and about 10% of cases develop after age 60.

Lifestyle factors, including smoking, alcohol abuse, and stress (in particular stressful work situations), appear to play a very strong role in cluster headaches. Smoking or alcohol use can trigger attacks. In a 2006 study, 70% of people with cluster headaches were current smokers. About half reported that alcohol (most commonly red wine) triggered an attack.

Evidence for genetic factors has been weak, but there is a growing body of research suggesting a family history in about 5 - 10% of patients. Some evidence suggests that cluster headaches in women may be more likely to be genetically based, particularly when they first occur at younger ages.

One study reported that 26% of cluster headache sufferers also had a personal history of migraines, and 33% had a family history of this headache. Studies have reported that about 15% of patients have both kinds.

Head injury may also increase the risk of cluster headaches. In one study, over 13% of patients reported a history of a head injury that caused loss of consciousness, and nearly a quarter had experienced a head injury without loss of consciousness.

Cluster headaches tend to occur during specific sleep stages and have been associated with several sleep disorders, including narcolepsy, insomnia, and sleep apnea.

Sleep apnea, a disorder in which a person stops breathing during the night, perhaps hundreds of times, is of particular interest. Studies have reported sleep apnea in 30 - 80% of patients with cluster headaches. One study suggested that in some people apneas may trigger cluster headache during the first few hours of sleep, making patients susceptible to follow-up attacks during the following midday to afternoon periods. Treating patients who have both disorders with a device called CPAP, which opens the airways, may help improve both conditions. [See In-Depth Report #65: Sleep apnea.]

The following conditions and substances might trigger cluster attacks:

Alcohol
High altitudes (trekking, air travel)
Bright light (including sunlight)
Exertion
Heat (hot weather, hot baths)
Foods high in nitrites (such as bacon and preserved meats)
Certain medications (including those that cause blood vessel dilation, such as nitroglycerin, and various blood pressure medications)
Cocaine

Triggers usually have an effect only during active cluster cycles. When the disorder is in remission, such triggers rarely set off the headaches.

Diagnosis

In two surveys, patients reported a delay of 1 - 6 years in the diagnosis of their headaches. In one of the surveys, migraine-like symptoms (light and sound sensitivity and nausea) were major reasons for the frequent misdiagnosis by family doctors. About a third of the patients sought help from dentists and another third from ear-nose-throat specialists. In most cases, patients were inappropriately treated for other types of headaches (including having sinus surgery).

For an accurate diagnosis, the patient should describe:

Duration and frequency of headaches
Recent changes in their character
Location of the pain
Type of pain (throbbing or steady pressure)
Pain intensity
Associated symptoms (visual disturbances or nausea and vomiting)
Behaviors during a headache
Snoring, sleep disturbances, and daytime sleepiness (which could relate to sleep apnea, a possible risk factor for cluster headaches)

The patient should try to recall what seems to bring on the headache and anything that relieves it. Keeping a headache diary is a useful way to identify triggers that bring on headaches:

Be sure to include all events preceding an attack. Often two or more triggers interact to produce a headache.
Tracking medications is an important way of identifying so-called rebound headaches, which can arise when drugs that are taken frequently are discontinued.
Be sure to attempt to define the intensity of the headache. It may be indicated by using a number system:

1 = Mild, barely noticeable

2 = Noticeable, but does not interfere with work or activities

3 = Distracts from work or activities

4 = Makes work or activities very difficult

5 = Incapacitating

To diagnose a chronic headache, the doctor will examine the head and neck and usually perform a neurologic examination, which includes a series of simple exercises to test strength, reflexes, coordination, and sensation. The doctor will also examine the eyes to rule out pressure build-up in the eye as a cause of headache. The doctor may ask questions to test short-term memory and related aspects of mental function.

As part of the diagnosis, a doctor should rule out other headaches and disorders. If the results of the history and physical examination suggest other or accompanying causes of headaches or serious complications, extensive imaging tests are performed.

Migraines. Cluster headaches are often misdiagnosed as migraines but they are quite different:

Frequency and Duration. Cluster headaches generally last 15 minutes to a few hours and can occur several times a day. A single migraine attack is continuous over the course of one or several days.
Behavior. Cluster headache sufferers tend to move about while migraine sufferers usually want to lie down.

Nevertheless, in both cases, the headache suffers can be highly sensitive to light and noise, which may make it difficult to distinguish between them.

Other Headaches. Other headaches that resemble migraines include SUNCT (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) and chronic paroxysmal hemicrania, which are other primary headaches, and some secondary headaches notably trigeminal neuralgia (TN), temporal arteritis, and sinus headaches. Cluster symptoms, however, are usually precise enough to rule out these other types of headaches.

Tear in the Carotid Artery. A tear in the carotid artery (which leads to the brain) can cause pain that resembles a cluster headache. People with this condition may even respond to sumatriptan, a drug used to treat a cluster attack. Doctors should consider imaging tests for patients with a first episode of cluster headache in which this event is suspected.

Orbital Myositis. An unusual condition called orbital myositis, which produces swelling of the muscles around the eye, may mimic symptoms of cluster headache. This condition should be considered in patients who have unusual symptoms such as protrusion of the eyeball, painful eye movements, or pain that does not dissipate within three hours.

Imaging tests of the brain may be recommended under the following circumstances:

If the results of the history and physical examination suggest neurologic problems
If headaches wake patients during the night
If new headaches develop in the elderly. In this age group, it is particularly important to first rule out age-related disorders, including stroke, hypoglycemia, hydrocephalus, and head injuries (usually from falls)
If headaches are becoming worse

Imaging tests are not recommended for patients with migraines and no other abnormal indications.

The following tests may be used:

A CT (computed tomography) scan may help rule out brain disorders or headaches caused by chronic sinusitis.
X-rays and other tests may also be used if sinusitis is strongly suspected.
A neck x-ray can reveal arthritis or spinal problems.
Other tests include an MRI (magnetic resonance imaging), EEG (electroencephalogram), lumbar puncture, ultrasound testing, and cerebral angiography, which are only performed if there is reason to suspect an underlying disease.

Headaches indicating a serious underlying problem, such as cerebrovascular disorder or malignant hypertension, are uncommon. (It should be emphasized that a headache is not a common symptom of a brain tumor.) People with existing chronic headaches, however, might miss a more serious condition believing it to be one of their usual headaches. Such patients should immediately call a doctor if the quality of a headache or accompanying symptoms has changed. Everyone should call a doctor for any of the following symptoms:

Sudden, severe headache that persists or increases in intensity over the following hours, sometimes accompanied by nausea, vomiting, or altered mental states (possible hemorrhagic stroke).
Sudden, very severe headache, worse than any headache ever experienced (possible indication of hemorrhage or a ruptured aneurysm).
Chronic or severe headaches that begin after age 50.
Headaches in the back of the head accompanied by other symptoms, such as memory loss, confusion, loss of balance, changes in speech or vision, or loss of strength in or numbness or tingling in arms or legs (possibility of small stroke in the base of the skull).
Headaches after head injury, especially if drowsiness or nausea are present (possibility of hemorrhage).
Headaches accompanied by fever, stiff neck, nausea and vomiting (possibility of spinal meningitis).
Headaches that increase with coughing or straining (possibility of brain swelling).
A throbbing pain around or behind the eyes or in the forehead accompanied by redness in the eye and perceptions of halos or rings around lights (possibility of acute glaucoma).
A one-sided headache in the temple in elderly people; the artery in the temple is firm and knotty and has no pulse; scalp is tender (possibility of temporal arteritis, which can cause blindness or even stroke if not treated).
Sudden onset and then persistent, throbbing pain around the eye possibly spreading to the ear or neck unrelieved by pain medication (possibility of blood clot in one of the sinus veins of the brain).

Managing Cluster Headaches

Patients with cluster headaches face significant difficulties in the management and treatment of their problems:

In two surveys, patients reported a delay in the diagnosis of their headaches of 1 - 6 years. In most of these cases, patients were inappropriately treated for other headaches (including having sinus surgery).
Treatment for cluster headaches is problematic because most attacks come on suddenly and occur daily, while episodic cycles may continue for weeks or months. Most oral medications used for other headaches act too slowly to have much effect on a cluster headache, which typically lasts about an hour. Injected or intravenous headache medications may work but they cannot be used on a daily basis. The emphasis in managing cluster attacks, therefore, is in preventing them. Verapamil and corticosteroid drugs are most commonly used for prevention.
Cluster headaches are difficult to study. First, they are very uncommon, so there are few well-controlled investigations of this problem. Second, the placebo response is very high in studies on cluster headaches, with 7 - 43% of patients responding to dummy treatments.

The most effective treatments for a cluster attack are:

Oxygen inhalation
Triptan drugs (injections of sumatriptan)

Relief can occur in 5 - 10 minutes.

Because effective therapy for cluster headaches is limited, most research efforts focus on the prevention of attacks during cluster cycles. A number of treatments are available and may be used alone or in combination. In general, the steps for preventive management are:

Transitional Medications. Patients should use headache medications (typically a triptan, a corticosteroid, or ergotamine) to control any attacks during the transition to on-going maintenance drugs.

Maintenance Drugs. Prevention of attacks during a cluster cycle is extremely important. Although patients with episodic or chronic cluster headaches may take different medications, there does not appear to be much difference in their effectiveness for either type. The following are the most commonly used preventive drugs:

Calcium-channel blockers. The calcium-channel blocker verapamil is most often used for preventing cluster headaches.
Corticosteroids. Tapered doses of corticosteroids, such as prednisone, may be useful for preventing episodic cluster headaches.
Lithium. Some studies suggest that lithium is the best drug for chronic cluster headaches.
Methysergide. This drug is a serotonin inhibitor and is sometimes used for episodic cluster headaches.
Antiseizure drugs. Of the antiseizure drugs, valproic acid is most often used. Others that may be useful include carbamazepine, gabapentin, and topiramate.
Ergotamine. Some doctors start with ergotamine, which is useful as a transitional medication.

Doctors have prescribed other drugs, including indomethacin, melatonin, beta blockers, tricyclic and other antidepressants, and capsaicin. Some patients may need a combination of medicines.

Lifestyle Changes. Patients should avoid the following:

Alcohol.
Foods containing nitrates or nitrites (such as smoked meats). No other dietary factors appear to play a role, for good or ill, in this disease.
Medications containing nitrates (such as nitroglycerin).
Smokers who can't quit should at least stop at the first sign of an attack and not smoke throughout a cycle.

One study suggested that vigorous physical exertion at the sign of an attack onset may help reduce or even abort an attack.

Treatment for Acute Attacks

Breathing pure oxygen (by face mask, for 15 minutes or less) is one of the most effective and safest treatments for cluster headache attacks. It is often the first choice. Inhalation of oxygen raises blood oxygen levels, therefore relaxing narrowed blood vessels.

Triptans are drugs that are usually used to treat migraine headaches. They can also help stop a cluster attack. Injections of sumatriptan (Imitrex) are the standard triptan treatment. Sumatriptan injections work within 15 minutes in about three quarters of cluster attacks. The nasal spray form is also effective, and generally provides relief within 30 minutes. The spray seems to work best for attacks that last at least 45 minutes, although some people find it does not work as well as the injectable form.

Newer triptans used for cluster headache treatment include rizatriptan (Maxalt), naratriptan (Naramig, Amerge), and zolmitriptan (Zomig). Several 2006 and 2007 studies of zolmitriptan nasal spray indicated it was effective for cluster headache relief with few side effects.

Side Effects. Many of the newer triptans may have fewer severe side effects than sumatriptan. Side effects of most triptans, however, may include:

Nausea
Dizziness
Muscle weakness
Heaviness or pressure in the chest
Tingling and numbness in the toes
Rapid heart rate

Complications of Triptans. The following are potentially serious problems with triptans.

Complications on the Heart and Circulation. Triptans narrow (constrict) blood vessels. Because of this action, spasms in the blood vessels may occur, which can cause stroke and heart attack. This is a rare but very serious side effect. Patients with a history of heart attack, stroke, angina, uncontrolled high blood pressure, peripheral artery disease, or heart disease should not use triptan drugs.
Serotonin Syndrome. Serotonin syndrome is a life-threatening condition that occurs from an excess of the brain chemical serotonin. Triptans, as well as certain types of antidepressant medications, can increase serotonin levels. These antidepressant drugs include serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft) and selective serotonin/norepinephrine reuptake inhibitors (SNRIs) such as duloxetine (Cymbalta) and venlafaxine (Effexor). It is very important that patients not combine a triptan drug with an SSRI or SNRI drug. Serotonin syndrome is most likely to occur when starting or increasing the dose of a triptan or antidepressant drug. Symptoms include restlessness, hallucinations, rapid heartbeat, tremors, increased body temperature, diarrhea, nausea, and vomiting. You should seek immediate medical care if you have these symptoms.

The following groups should avoid triptans or take them with caution and only under doctor supervision:

Anyone with a history or any risk factors for stroke, uncontrolled diabetes, high blood pressure, or heart disease.
People taking antidepressants that increase serotonin levels.
Pregnant women. Studies on the effects of triptans in this group are limited. One study suggested a higher incidence of preterm deliveries in pregnant women taking sumatriptan. No higher rates of still births or birth defects were reported. In general, pregnant women should avoid any medications if possible.

Injections of the ergotamine-derived drug known as dihydroergotamine (DHE) can stop cluster attacks within 5 minutes in many patients, offering benefits similar to injectable sumatriptan. Ergotamine is also available in the form of a nasal spray, rectal suppositories, and tablets. Ergotamine can have dangerous drug interactions with many medications. All ergotamine products approved by the Food and Drug Administration (FDA) contain a "black box" warning in the prescription label explaining these drug interactions. In 2007, the FDA pulled 15 unapproved older ergotamine products off the market, in part because they lacked this warning label.

Methysergide (Sansert) is another ergot-based drug that is used for preventing episodic cluster headaches. (It is not very effective for chronic cluster headaches.) Improvement usually occurs within a few days, although it may be delayed for up to 2 weeks. Prolonged methysergide therapy can cause serious side effects, including scarring of internal organs, so it cannot be used long term. This is not usually a problem for patients with cluster headaches, since they need the drug only for about 4 - 6 weeks. Nevertheless, patients should immediately report to their doctors any of the following symptoms: cold, numb, and painful hands and feet; leg cramps on walking; any type of back or chest pain.

Lidocaine, a local anesthetic, may be useful in nasal-spray or nasal-drop form for stopping cluster attacks. Some reports suggest that it is helpful for most patients within about 40 minutes.

Preventive Medications

Calcium-channel blockers, commonly used to treat heart disease, are important drugs for preventing cluster headaches. Verapamil (Calan) is the standard calcium-channel blocker used for headache prevention. Constipation is a common side effect. Verapamil can also cause irregular heartbeats (arrhythmia), according to a 2007 study in Neurology. Patients who take verapamil for cluster headaches should have frequent electrocardiograms (EKGs) to monitor any potential development of arrhythmia.

People taking calcium-channel blockers should not stop taking the drug abruptly. Doing so can dangerously increase blood pressure. Overdose can cause dangerously low blood pressure and slow heart beats. Drinking grapefruit juice or eating grapefruit with these drugs can enhance their potency, sometimes to toxic levels that can cause heart failure in patients with heart disease.

Lithium (Eskalith, Lithane, Lithobid, Lethonate, Lithotabs), commonly used for bipolar disorder, can also help prevent cluster headaches. The patient usually receives benefit within 2 weeks of starting to take the drug, and often within the first week. Lithium may be used alone or with other drugs.

Side Effects. Side effects include:

Trembling hands
Nausea
Increased urine output
Some loss of coordination

More severe reactions, which occur at higher blood levels, are:

Convulsions
Uncontrolled jerky movements in arms and legs
Blurred vision
Vomiting
Stupor
Coma

Very high blood levels of lithium can be fatal.

Long-Term Side Effects. Even for patients who do not have a toxic response, long-term use of lithium is not without problems. Some patients may experience:

An unpleasant taste in the mouth
Hair loss
Weight gain (a frequent reason why many patients stop taking lithium)
Skin eruptions that can resemble acne (lithium can also worsen psoriasis in patients who have this condition)
Thyroid problems -- Up to 20% of patients who take lithium develop symptomatic hypothyroidism (low thyroid), and another 20 - 30% develop hypothyroidism without symptoms
Increased risk for diabetes
Blunted sexual drive
Dulled emotions and mental acuity
Memory loss
Lack of motor coordination
Reduced sensitivity to light -- This may slightly affect color recognition and cause problems with night driving; patients wear sunglasses outside and avoid extensive exposure to bright light

Drug Interactions. Because lithium is eliminated from the body by the kidneys, any drugs or dietary factors that slow the kidneys' actions may increase lithium blood levels and should be used with great caution. Such drugs include:

Nonsteroidal anti-inflammatory drugs (NSAIDs)
Thiazide diuretics
ACE inhibitors

There have been reports of interactions between lithium and certain drugs commonly used in combination, including:

Antipsychotics
Anticonvulsants
Calcium-channel blockers

Other Factors That Affect Lithium Levels. In addition to drugs, other factors may affect lithium levels, including:

Seasonal change
Menstrual cycle (lithium levels may drop during the premenstrual phase)
Weight loss
Changes in salt intake
Dehydration
Diarrhea

Patients should contact their doctor if they have any suspicious symptoms or illnesses.

Valproate. The anti-epileptic drug valproate (valproic acid, divalproex sodium, Depakene, Depakote) has been used with some success for preventing cluster headaches. It controls pain and reduces the frequency of attacks by more than half in many people with episodic or chronic cluster headaches. Side effects include nausea, vomiting, heartburn, increased appetite with weight gain, hand tremors, irritability, and temporary hair thinning and loss (taking zinc and selenium supplements may help reduce this effect). It can also cause birth defects and, in rare cases, liver toxicity.

Topiramate. Other, newer anti-seizure drugs that have fewer side effects are being investigated for chronic headaches. Studies on topiramate (Topamax) are promising. In small trials of topiramate, up to 87% of patients achieved remission, and 60% achieved a complete response. Still, about 25% of patients stop using it, either because it doesn't work or because the side effects are intolerable. They can include drowsiness, mood changes, tremor, and confusion.

Gabapentin. Another anti-seizure drug that has shown some benefit in isolated cases is gabapentin (Neurontin). Research on this drug in patients with cluster headaches, however, remains very limited.

Side Effects of Valproate and Other Anti-Seizure Drugs. The side effects given here are mostly associated with valproate. Other anti-seizure drugs have similar effects and some specific ones of their own. Most are usually minor, occurring early in therapy, and then subsiding. Those of valproate include:

Gastrointestinal problems (nausea, vomiting, heartburn)
Visual disturbances
Ringing in the ear
Hair loss
Weight changes (weight gain is a significant problem with valproate, while weight loss occurs with topiramate)
Agitation
Odd movements
In women, menstrual irregularities and a higher risk for polycystic ovary syndrome (PCOS)

Very serious side effects are rare but include the following:

Liver damage
Convulsions
Coma
Pancreatitis (inflammation of pancreas) in adults and children
Significant increase in risk for birth defects in pregnant women

A nasal spray form of capsaicin called civamide (Zucapsaicin) has shown promise in the prevention and treatment of cluster headaches. Capsaicin is a component of hot red peppers that seems to reduce substance P, a chemical in the body that contributes to inflammation and the delivery of pain impulses. In a small study, daily use of intranasal civamide resulted in more than a 50% reduction in headaches. Side effects include a burning sensation and excessive tearing.

Transitional medications are used after cluster episodes to stabilize the patient until preventive maintenance becomes effective.

Corticosteroid drugs (also called steroids) are very useful as transitional drugs for stabilizing patients after an attack until a maintenance drug, such as a calcium-channel blocker, begins to take effect. Prednisone (Deltasone) and dexamethasone (Decadron) are the standard steroid drugs used for short-term cluster headache transitional treatment. These drugs are typically taken for a week and then gradually tapered off. If headaches return, the patient may start taking the steroid again. Unfortunately, long-term use of steroids can lead to serious side effects so they cannot be taken for on-going prevention.

Angiotensin Receptor Blockers. Angiotensin receptor blockers (ARBs) are used to treat high blood pressure. Candestan (Atacand) is being investigated as a potential preventive medication for cluster headache.

Botulinum. Botulinum toxin A (Botox) injections are being used for several conditions requiring muscle relaxation, including smoothing wrinkles. (This potentially deadly toxin is very safe when minuscule amounts are injected into small muscles.) Botox has shown promise for migraine and tension headache sufferers and is now being studied for cluster headaches as well.

Melatonin. Small reports indicate that melatonin, a brain hormone that helps to regulate the sleep-wake cycle, may help prevent episodic or chronic cluster headaches. Melatonin supplements are sold in health food stories, but as with most natural remedies, the quality of different preparations varies, and they have not been rigorously tested for safety or effectiveness. Hormones such as melatonin are powerful substances, and additional studies are needed.

Glucosamine. There have been some reports that glucosamine, an alternative remedy commonly used for osteoarthritis, may prevent migraine attacks. Some researchers theorize this substance may reduce inflammation that affects nerves involved in vascular headaches. Whether it has any effect on cluster headaches is unknown.

Additional Therapies. Many patients with cluster headaches try alternative remedies for relief of pain. Treatments may include acupuncture, herbs, chiropractic, homeopathic remedies, reflexology, hypnosis, spiritual therapies, massage, aromatherapy, relaxation techniques, and yoga.

Surgery

Surgical intervention may be considered for patients with chronic cluster headaches that do not respond to treatments. Patients whose headaches have not gone into remission for at least a year may also be candidates for surgery. Most surgical approaches for cluster headache are still considered experimental. Surgy has shown limited success and can have distressing side effects. However, some surgical techniques, such as deep brain electrical stimulation, are showing promise.

Deep brain stimulation (also called neurostimulation) may relieve chronic cluster headaches in some patients who do not respond to drug therapy. A similar technique is approved for treating the tremors associated with Parkinson’s disease. The surgeon implants a tiny wire in a specific part of the hypothalamus. The wire, meanwhile, receives electrical pulses from a small generator implanted under the collarbone.

Although only a handful of patients have been treated, results to date are promising. Some patients have remained completely free of pain for an average of more than 7 months when the electrode is switched on. When the device is turned off, headaches reappear within days to weeks. The procedure is reversible and appears to be generally safe, although a few cases of fatal cerebral hemorrhage have occurred.

Occipital nerve stimulation is being investigated as a less invasive alternative to hypothalamus stimulation. Two 2007 studies in Lancet and Lancet Neurology reported promising results in a small group of patients with cluster headaches. Some patients became pain-free, while others had reduced frequency of headache attacks. Researchers suggest that occipital nerve stimulation may be less risky than deep brain stimulation.

The vagus nerve runs between the brain and the abdomen. Vagus nerve stimulation (VNS) is a surgical procedure in which a small generator is placed under the skin on the left side of the chest. A surgeon makes a second incision in the neck and connects a wire from the generator to the vagus nerve. A doctor programs the generator to send mild electrical pulses at regular intervals. These pulses stimulate the vagus nerve.

VNS is sometimes used to treat epilepsy and depression that does not respond to drugs. It is also being investigated as a possible treatment for chronic migraine and cluster headaches. In a 2005 study of six patients, VNS improved headache and helped a few patients return to work.

Percutaneous Radiofrequency Retrogasserian Rhizotomy. Percutaneous radiofrequency retrogasserian rhizotomy (PRFR) generates heat to destroy pain-carrying nerve fibers in the face. Small studies have reported good to excellence results in 83 - 92% patients. Unfortunately complications are common and include numbness, weakness during chewing, changes in tearing and salivation, and facial pain. In severe, but rare, cases, complications include damage to the cornea and vision loss.

Percutaneous Retrogasserian Glycerol Rhizolysis. Percutaneous retrogasserian glycerol rhizolysis (PRGR) is a less invasive technique than PRFR and has fewer complications. It involves injections of glycerol to block the facial nerves that cause the pain. In one study, 83% of patients reported immediate relief after one or two injections. Cluster headaches recurred, however, in about 40% of the patients.

Microvascular Decompression of the Trigeminal Nerve. Microvascular decompression frees the trigeminal nerve from any blood vessels that are pressing against it. In one study, over 73% of patients reported at least 50% relief. Half of these patients reported 90% relief, but the level of benefit fell to less than 50% over time. Repeat procedures are rarely successful. The procedure is risky, and possible complications include nerve and blood vessel injury and spinal fluid leakage. It does not, however, have the common nerve damage effects in the face that PRFR does.

Resources

www.i-h-s.org -- International Headache Society
www.headaches.org -- National Headache Foundation
www.americanheadachesociety.org -- American Headache Society
www.aan.com -- American Academy of Neurology
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.ouch-us.org -- Organization for Understanding Cluster Headaches
www.clusterheadaches.com -- Support group for people with cluster headaches

References

Burns B, Watkins L, Goadsby PJ. Treatment of medically intractable cluster headache by occipital nerve stimulation: long-term follow-up of eight patients. Lancet. 2007 Mar 31;369(9567):1099-106.

Cittadini E, May A, Straube A, Evers S, Bussone G, Goadsby PJ. Effectiveness of intranasal zolmitriptan in acute cluster headache: a randomized, placebo-controlled, double-blind crossover study. Arch Neurol. November 2006. [Epub ahead of print 11 September 2006]

Cohen AS, Matharu MS, Goadsby PJ. Electrocardiographic abnormalities in patients with cluster headache on verapamil therapy. Neurology. 2007 Aug 14;69(7):668-75.

Magis D, Allena M, Bolla M, De Pasqua V, Remacle JM, Schoenen J. Occipital nerve stimulation for drug-resistant chronic cluster headache: a prospective pilot study. Lancet Neurol. 2007 Apr;6(4):314-21.

Rapoport AM, Mathew NT, Silberstein SD, Dodick D, Tepper SJ, Sheftell FD, Bigal ME. Zolmitriptan nasal spray in the acute treatment of cluster headache: a double-blind study. Neurology. 2007 Aug 28;69(9):821-6.

Rose KM, Wong TY, Carson AP, Couper DJ, Klein R, Sharrett AR. Migraine and retinal microvascular abnormalities: the Atherosclerosis Risk in Communities Study. Neurology. 2007 May 15;68(20):1694-700.

Schurks M, Kurth T, de Jesus J, Jonjic M, Rosskopf D, Diener HC. Cluster headache: clinical presentation, lifestyle features, and medical treatment. Headache. 2006 Sep;46(:1246-54.

Sostak P, Krause P, Forderreuther S, Reinisch V, Straube A. Botulinum toxin type-A therapy in cluster headache: an open study. J Headache Pain. 2007 Sep 24; [Epub ahead of print]

Van Vliet JA, Eekers PJ, Haan J, Ferrari MD; Dutch RUSSH Study Group. Evaluating the IHS criteria for cluster headache -- a comparison between patients meeting all criteria and patients failing one criterion. Cephalalgia. 2006 Mar;26(3):241-5.

Review Date:
10/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Multiple sclerosis

FitSugar — Wed, 08 Oct 2008 17:35:12 -0700

In This Report

Highlights
Introduction
The Autoimmune Disease Proc...
Symptoms
Causes
Risk Factors
Complications
Diagnosis
Treatment
Drug Treatment
Other Treatments
Treating the Complications...
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Gender and Multiple Sclerosis (MS)

MS is increasingly affecting women, according to research presented at the 2007 annual conference of the American Academy of Neurology. Researchers found that in the 1940s, women were twice as likely as men to be diagnosed with MS. By 2000, women were about four times more likely than men to develop MS. Experts are uncertain why this ratio is growing.

Family History

If MS runs in your family, there’s a chance you may develop the disease at the same age that other family members did, suggests a 2007 Neurology study. However, family history does not predict disease course or severity.

Vitamin D

Higher blood levels of vitamin D may reduce the risk for MS, at least among Caucasians, indicates a 2007 study in the Journal of the American Medical Association. (The researchers found no protective effect for African-Americans or Hispanics.) However, until further research is conducted, doctors do not recommend taking vitamin D supplements for MS prevention.

Infections and Symptom Relapse

Both viral and bacterial systemic infections can trigger relapses, according to a study in Neurology. Researchers found that relapses and new brain lesions appeared within 2 weeks after an infection.

Drug Research

Natalizumab (Tysabri) may help reduce vision loss in patients with relapse-remitting MS, indicates a 2007 Neurology study. In 2006, the FDA enforced safety restrictions on the use of this drug due to cases of progressive multifocal leukoencephalopathy (PML), a rare brain disorder. Since the restrictions were put in place, no new cases of PML have been reported.
Glatiramer acetate (Copaxone) shows little benefit for primary progressive MS, according to a 2007 study in Annals of Neurology.
Testosterone gel may help men with relapse-remitting MS, suggests a small study published in 2007 in the Archives of Neurology.

Introduction

Multiple sclerosis (MS) is a disease of the central nervous system (CNS), the nerves that comprise the brain and spinal cord. It has two major features:

Destruction of myelin, a fatty insulation covering the nerve fibers, is the main characteristic of MS. The end results of this process, called demyelination, are multiple patches of hard, scarred tissue called plaques. (Multiple sclerosis is well named. Sclerosis comes from the Greek word skleros, which means hard.)
Destruction of axons, the long filaments that carry electric impulses away from a nerve cell, is also a major factor in the permanent disability that occurs with MS.

Myelin is the layer that forms around nerves. Its purpose is to speed the transmission of impulses along nerve cells.

The symptoms, severity, and course of MS vary widely depending partly on the sites of the plaques and the extent of the demyelination. Experts generally group multiple sclerosis into two major symptom categories:

Relapsing-remitting
Chronic-progressive

Chronic-progressive MS is often subcategorized as primary-progressive, secondary-progressive, and progressive-relapsing.

Recent evidence suggests that the disease process starts long before symptoms begin. By the time symptoms appear, there are often already signs of brain and spinal cord atrophy. The cause of MS is unknown, and it cannot be prevented or cured. It is not fatal, however, and great progress is being made in treating it and identifying underlying mechanisms that trigger this disease.

Relapsing-remitting multiple sclerosis generally occurs in younger people and is the most common form of MS. It generally follows this course:

Most patients first experience a single attack of symptoms called a clinical isolated syndrome, which typically occurs between the ages of 20 - 40 years. Once a second attack occurs, the patient is considered to have relapsing-remitting multiple sclerosis.
The characteristic feature of relapsing-remitting MS is the attack (also referred to as relapse, flare-up, or exacerbation), which is a bout of specifically MS symptoms (facial pain, Lhermitte’s sign, or bladder instability) that lasts at least 24 hours and typically several days. Such attacks are fairly mild in about half of patients with this form of MS.
The disease then goes into remission (when symptoms improve or disappear), usually for about 4 - 8 weeks. To be considered in remission, attacks need to be separated by at least 30 days. Remission periods may be spontaneous or induced by immunosuppressive drugs. A person with multiple sclerosis in remission may have subtle attacks and not realize it. For example, hands may be a little numb for a few days, or there may be slight awkwardness in gait or coordination.
Remissions are almost always followed by relapses, in which symptoms flare-up or the patient experiences a period of deteriorating ability.

About 20% of patients with relapsing-remitting MS experience little or no progression after a first attack for long periods of time, although by 25 years most patients have converted to a progressive phase.

The term chronic-progressive multiple sclerosis is used to describe cases in which symptoms continue to worsen slowly without remission. About 20% of multiple sclerosis patients (usually those whose first symptoms occur after age 45) have the chronic-progressive form without first developing relapsing-remitting MS. Chronic-progressive MS generally follows a downhill course, but its severity varies widely. Three variants are commonly used to define this patient group:

Secondary-Progressive MS (SPMS). SPMS is the natural evolution of relapsing-remitting MS and develops in about half of patients during the first 10 years and nearly all of them within 25 years. It follows a progressive course of nerve and muscle deterioration with occasional acute flare-ups, remissions, and plateaus.
Primary-Progressive MS (PPMS). PPMS progresses continuously and gradually from the first onset of symptoms and has no remissions. It occasionally levels off, and minor improvement is even possible. This occurs in about 10% of patients, who tend to be older than average at the time of diagnosis.
Progressive-Relapsing MS (PRMS). PRMS is progressive from the start with acute symptom flare-ups, but may have some relapses with continued deterioration between them. It occurs in less than 5% of patients.

Because the natural courses of primary-progressive and progressive-relapsing MS are similar, some experts believe this distinction is unnecessary.

Click the icon to see an image depicting multiple sclerosis.

The Autoimmune Disease Process

Multiple sclerosis is referred to as an autoimmune disease. The general theory for the development of MS is that a genetically damaged immune system is unable to distinguish between virus proteins and the body’s own myelin and so produces antibodies that attack. In other words, the body becomes allergic to itself, a condition known as autoimmunity.

Autoimmunity may develop when the body's immune system is damaged by genetic or environmental factors or both, causing it to attack its own tissues. In the case of MS, the immune system attacks the tissues that make up myelin:

Myelin is made from layers of cell membranes that are produced in the brain and spinal cord by specialized cells called oligodendrocytes. The destruction of this myelin sheath during the disease process is the hallmark for multiple sclerosis.
The myelin coat is distributed in segments along the axons, the long filaments that carry electric impulses away from a nerve cell.
The segments are separated from each other by tiny clusters called nodes of Ranvier, which house channels for sodium ions. These sodium ions are important for boosting the electrical charge required to pass signals from one nerve to another.
As the myelin insulation is destroyed, signals transmitted from nerve cell to nerve cell throughout the central nervous system are disrupted.
Experts once believed that axons themselves were spared during the disease process. Research, however, has shown that many are severed in MS and, in fact, axon destruction appears to start at an early stage in the disease and may be a major cause of its irreversibility.

The body often makes corrective actions to offset the effects of the nerve cell destruction:

For example, researchers have observed an increase in the density of the sodium channels, which carry electric charges. By increasing their numbers, the nerve cells can continue to communicate, in spite of the loss of myelin.
The nerves also retain some capacity to remyelinate (to restore the insulating myelin).

Such processes are probably responsible for the remissions that most patients experience. Unfortunately, the disease process nearly always eventually outpaces these corrective actions.

The Normal Immune Response.

The most important critical immune factors in the disease process are white blood cells called lymphocytes, which consist of T cells and B cells. These cells are the warriors in the immune defense system.
Receptors on T cells acquire the ability to recognize specific molecules called antigens. Antigens are typically proteins from infecting organisms, such as bacteria or viruses, and perceived as a threat to the body.
Once the antigen is identified, specific T cells, called helper T cells, trigger the B cells to release antibodies. These molecules are designed to attach to and destroy the targeted antigen.

Autoimmunity.

Multiple sclerosis, and probably all autoimmune diseases, involves an error in the education of T cells, which makes them unable to distinguish self from non-self.
In multiple sclerosis, the miseducated T cells mistake molecules in the body's own myelin as a foreign antigen. Such targets are referred to as self-antigens.
In response to detection of these self-antigens, the T cells set off the usual cascading immune events, including the release of B lymphocytes, to rid the body of the perceived threat.
The B lymphocytes fire off antibodies as usual, but in this case they are referred to as autoantibodies, because they are attacking antigens that belong to the body's own self.
In MS, the immune system is tricked into targeting self-antigens that are myelin proteins, the fatty insulation covering the nerve fibers. Another autoantibody target may be the oligodendrocytes themselves -- the specialized cells that make up myelin.
To make matters worse, the process perpetuates through a cascading series of events in which the B cells and T cells continue to interact, creating numerous different self-antigens. The attacks continue and, in the process, the original self-antigen is unrecognizable.

Cytokines and the Inflammatory Response. The inflammatory response is the product of an overactive immune system and is a major destructive force in an autoimmune disease.

Once the lymphocytes have launched a response to an antigen, they also release masses of other white blood cells to gather at the injured or infected site.
The major players in this response are white blood cells called leukocytes. Researchers are particularly interested in leukocytes called cytokines. These are small powerful proteins that, in tiny amounts, are indispensable for healing. When they are overproduced, however, which occurs in MS, they play a major role in the destructive process.
Their intensive convergence on the affected area causes it to become inflamed and injurious to the very cells they are designed to protect. Under normal conditions, this inflammatory process is controlled and self-limiting, but in people with autoimmune diseases such as multiple sclerosis, the process persists and damage occurs in the surrounding tissues.

Important cytokines in MS appear to be tumor necrosis factors, interleukin-12, and interferon-gamma. Other cytokines, including interleukin-10 and transforming growth factor beta, may play a protective role and help block inflammatory activity.

The inflammatory response may trigger the disease, but afterward a progressive course takes over that does not appear to be related to inflammation. Experts have found that destruction of axons, the long filaments that carry electric impulses away from a nerve cell, is a major feature of multiple sclerosis. In fact, it may be the major cause of permanent disability that occurs with this disease. Microscopic studies reveal that axons are injured early on as "bystanders" while myelin is being peeled off. As the disease progresses, these weakened and exposed axons degenerate further. Most of the damage occurs early in the disease process and decreases over time, although some destruction can still be observed years and decades afterward. Such evidence is having significant effect on approaches to treatment and research.

Symptoms

Most patients first experience multiple sclerosis as a single attack of symptoms called a clinical isolated syndrome, which typically occurs between the ages of 20 - 40 years. Once a second attack occurs, the patient is considered to have relapsing-remitting multiple sclerosis. Much less commonly, the disease is progressive from the start and symptoms are more or less continuous.

Early symptoms may include the following:

Optic neuritis and other problems in the eye. Optic neuritis, which is inflammation of the nerves in the eye, affects over 50% of patients and is the first symptom in about 16% of patients. Symptoms include unclear or doubled vision, usually in one eye. Some people see a shimmering effect. Patients may also experience pain or involuntary jerking or movement of the eye (called nystagmus). In 20% of people with this condition, MS develops within 2 years after the onset. In 45 - 80%, MS develops within 15 years. About 17% of people eventually experience impaired eye movement.
Fatigue. Fatigue is typically worse in the afternoon and may be accompanied by an increase in body temperature. At the onset, this occurs in about 20% of patients, but as the disease progresses, this is a significant symptom in nearly all patients.
Changes in sensations in the arms and legs. Patients can experience heaviness, weakness, or clumsiness in the limbs. Tingling or loss of sensations can also occur, most commonly in the legs. The first symptoms for patients with primary progressive MS often develop slowly in the upper legs.
Muscle weakness in the legs and poor coordination.
Lhermitte’s sign. This is an electrical sensation that runs down the back and into the legs, which is produced by bending the neck forward.
Spasticity. Spasticity is the inability to control muscle tone and leads to spasms and stiffness. It is very common in MS.
Disturbances in the bladder.

In addition to the persistence of early symptoms, some patients experience the following symptoms as the disease progresses:

Imbalance and dizziness.
Tremors.
Facial pain.
Spasm-related symptoms. They include burning, itching, aching, quivering sensations. They usually occur in the extremities and last seconds to minutes.
Speech difficulties.
Difficulty swallowing.
Symptoms in the gastrointestinal, urinary, and genital tracts. Possible sexual dysfunction and loss of bowel and bladder control in severe cases.
Emotional mood swings. Depression is very common. About 10% of patients suffer from psychosis (manic depression and paranoia). About 5% of patients with severe MS experience uncontrolled and extreme mood swings called the laughing/weeping syndrome.
Problems in concentration and memory.
Hearing loss.

Infections. Viral infections have long been known to worsen MS symptoms. An important 2006 study indicated that bacterial infections can also trigger MS relapses. In the study, relapses appeared within 2 weeks of a viral or bacterial infection.

Heat. Heat, whether generated by ambient temperature, infection, or physical activity, worsens MS symptoms in about 60% of patients.

Stress. There is a strong correlation between severe stress and exacerbation of MS symptoms. For example, in one study, 85% of instances of MS exacerbations were associated with stressful events that occurred within an average of 14 days before the episode. Stress is not a cause of MS, however.

Trauma. Some experts believe that injury (trauma) to the head, neck, or upper back may trigger new or recurrent symptoms by disrupting the blood-brain barrier and allowing immunological attacks on the brain. This is a highly controversial theory, however, with very little supporting evidence.

Causes

The cause, or causes, of multiple sclerosis remains a mystery. Genetic factors certainly play a role in MS. No single gene, however, is likely to be responsible for causing MS. Rather, the current theory is that the disease occurs in people with a genetic susceptibility who are exposed to some environmental assault (a virus or a toxin) that disrupts the blood-brain barrier. Immune factors converge in the nerve cells and trigger inflammation and an autoimmune attack (a self-attack) on myelin and axons. Still, a number of disease patterns have been observed in patients, and some experts believe that MS may prove to be not a single disorder, but may represent several diseases with different causes.

Some research suggests that all autoimmune diseases are basically due to the same genetic error. A 2001 study found, for example, that the T cell immune factors in type 1 diabetes target the same self-antigens as in multiple sclerosis (MS). Many questions are unanswered, however. It is not known why the diseases develop in different locations to cause separate disorders. Nor, why some autoimmune events occur in everyone but not everyone develops an autoimmune disease.

Genetic factors probably play some role in making a person susceptible to the disease process leading to multiple sclerosis. In particular, abnormalities in the human leukocyte antigen (HLA) region located on chromosome 6 appear to be more prevalent among people with MS. Researchers theorize, however, that a combination of genes (not a single gene) is implicated in the development of MS, and the risk for someone inheriting all of these genetic factors is less than 5%. Advanced techniques called microarray technologies are now making it possible to scan hundreds of genes and identify those most likely to be contributors to MS. Genetic research may also pave the way for the development of new drugs to treat this disease. For example, researchers have recently identified the Olig1 gene as a key regulator in repairing damaged myelin-producing cells.

Infectious organisms, most likely viruses, are the top suspects for triggering the autoimmune response in people genetically susceptible to MS. There are a number of reasons for this belief:

The geographical distribution of the disease. The number of MS cases increases the further one gets from the equator in either direction.
Multiple sclerosis clusters. Four separate clusters of multiple sclerosis outbreaks occurred between 1943 - 1989 in the Faroe Islands, located between Iceland and Scandinavia. During World War II, this region was occupied by British troops. The incidence of MS increased each year for 20 years after the war, leading some researchers to think that the troops might have brought with them some disease-causing organism. In fact, one theory suggests that these findings offer evidence that MS is a sexually transmitted infection that occurs during adolescence. For example, the disease clusters observed in the Faroe Islands could be related to high sexual activity between the troops and local young women. A high incidence of MS is found in countries with a high degree of sexual permissiveness. MS is very rare in traditional cultures, but increases in people from these regions when they immigrate to industrialized Western nations.
Viral similarity to myelin. Some viruses are strikingly similar to the myelin protein and may therefore cause confusion in the immune system, causing the T cells to continue to attack their own protein rather than the viral antigen. More than one antigen may be involved; some may trigger the disease, and others may keep the process going.

Infectious Organisms Under Suspicion. Although many infectious microorganisms have been investigated, no one organism has emerged as a proven trigger. It is possible that different patients may be affected by different organisms, and that infections cause some, but not all, cases of MS. Organisms that are at the top of the suspect list are those that can affect the central nervous system. The following are three primary suspects:

HHV-6. Herpesvirus 6 (a form of herpesvirus that causes roseola, a benign disease in children) is also known to cause encephalitis (brain inflammation) in patients with impaired immune systems. A number of studies have reported higher than normal rates of HHV-6 infection in patients, and some experts believe that may be important in MS. Other experts argue, however, that nearly everyone harbors this virus and there is still no evidence of a causal relationship. Other herpes viruses can also infect brain cells. They include herpes simplex 1 and 2 (the causes of oral and genital herpes), varicella-zoster virus (the cause of chicken pox and shingles), and cytomegalovirus.
Epstein-Barr virus (EBV). Evidence suggests an association between EBV, the cause of mononucleosis, and MS. EBV is an extremely common virus and another member of the herpes virus family. Nearly all people have been exposed to EBV. However, researchers have discovered that people who are especially sensitive to the virus and have unusually high levels of EBV antibodies may have a greater risk of developing MS. Scientists are still uncertain if EBV is a cause of MS. EBV has also been linked to other autoimmune diseases such as lupus.
Chlamydia Pneumoniae. This atypical bacterium has been associated with persistent inflammation. A few studies have reported significantly higher rates of previous Chlamydia infection in patients with MS than in individuals without MS. An important group of 2000 studies reported no connection at all between Chlamydia and MS, and any experts now believe there is no strong evidence linking the microbe to MS. It is still possible, however, that the infection, which can cause widespread inflammation, plays a role early in the course of the disease in some individuals.

Other viruses that have been investigated include measles virus, adenovirus, and the retroviruses (HIV, HTLV-I, and HTLV-II), but none have emerged as having any importance.

Note on Vaccinations: Concerns about a link between the hepatitis B vaccine and MS led France to halt a major vaccination program in 1998. Subsequent research investigating whether the hepatitis B vaccine is indeed associated with an increased risk of MS has yielded mixed results. It appears that the vaccine would be, at most, a contributing -- but not the sole -- factor in MS development. At present, the evidence has not warranted any change in American immunization policies. Research has ruled out a link between any other vaccinations, such as or influenza or tetanus, and relapses of MS.

Risk Factors

An estimated 400,000 Americans and 2.5 million people worldwide suffer from MS.

Age. Onset occurs between the ages of 20 - 40 years in 70% of patients with the average age being 30 and the peak incidence occurring in the mid-twenties. The disease can still occur in both younger and older individuals. It rarely develops before age 15 or after age 60, however.

Gender. MS is more common among women than men. The gender gap is strongest among people who develop MS at a younger age. According to research presented at the 2007 American Academy of Neurology annual conference, the ratio between women to men has been growing. Researchers found that in the 1940s, the ratio of women to men with MS was 2 to 1. By 2000, the ratio had grown to 4 to 1. However, some research indicates that men may be more disabled by the disease than women.

Ethnicity. Multiple sclerosis occurs worldwide but is most common in Caucasian people of northern European origin, especially those of Scottish descent. It is extremely rare among Asians, Africans, and Native Americans. Specific groups (gypsies, Eskimos, Bantus) have never reported a case. While the risk of MS for African-Americans is around half of that for Caucasians, a recent study suggested that African-Americans are more likely to develop a more aggressive form of the disease and to suffer impaired mobility.

Geography. The risk for MS is higher in different regions of the world. In general, MS is more prevalent in temperate regions than in the tropics. Specifically, prevalence is highest in northern and central Europe (except northern Scandinavia), Italy, southern Australia, and northern regions of North America. Middle-risk areas include southern Europe (except Italy), southern US, northern Australia, and northern Scandinavia. Low-risk areas include parts of Africa and Asia, the Caribbean, Mexico, and possibly northern South America. It is unclear whether this pattern is attributable to environmental factors, genetics, or both.

Family History. A family history of the disease also puts people at risk for MS, although the risk for someone inheriting all the genetic factors contributing to MS is only about 2 - 4%. A 2007 study indicated that family members who have MS tend to develop the disease at around the same age. However, family history does not predict whether one family member will experience the same disease severity as another family member.

Cow's Milk During Early Infancy. Breast milk contains factors that may help regulate the immune response, and there is some evidence that infants fed only on cow's milk may have a higher risk for either diabetes type 1 (another type of autoimmune disease) or multiple sclerosis later in life. Studies on national differences in diabetes suggest that the risk may vary with different milk proteins, suggesting that not all cow's milk is the same and that some proteins carry higher risks than others.

The Hygiene Theory: Early Infections as Protection Against Allergies and Autoimmune Diseases. Over the past decades, there has been a dramatic increase in asthma, allergies, and autoimmune diseases, such as multiple sclerosis, Crohn's disease, and type 1 diabetes. One theory blames this rise on the reductions in childhood infections that have occurred with modern hygiene and antibiotic use. Studies supporting this have observed a higher incidence of allergies and autoimmune diseases, including MS, among populations with good hygiene and in animals that have been raised in a germ-free environment. The basic theory rests on the idea that early infections stimulate production of specific immune factors that protect against allergies and autoimmune diseases. The exact mechanisms of these effects are as yet unknown.

Vitamin D. Higher blood levels of vitamin D have been associated with a lower risk for MS, at least among Caucasians. (Studies have not shown that vitamin D has a protective effect for other racial groups.) However, there is not yet enough evidence to indicate that taking vitamin D supplements can help prevent MS.

Exposure to Sunlight. In a 2003 study, higher exposure to sunlight during childhood and early adolescence was associated with a lower risk for MS, perhaps because UV radiation produces higher levels of vitamin D, which has been associated with protection against MS. The effect of sunlight during winter seemed to be more protective than summer light. Unfortunately, higher exposure to sunlight also coincides with a higher risk for skin cancer, which is far more common than MS.

Estrogen and Oral Contraceptives. Higher estrogen levels may temporarily lower the risk of developing multiple sclerosis. Studies indicate that oral contraceptives (which contain estrogen) and pregnancy delay the onset of multiple sclerosis. The risk for a first clinical attack increases, however, in the 6 months after a woman gives birth.

Complications

Multiple sclerosis is not a fatal disease. Some data suggest that it shortens the average life span by only about 6 or 7 years. Still, in about half of MS cases, patients die of complications of the disease, and the disease has significant negative emotional and physical consequences. Suicide rates among patients with MS are higher than average.

The severity of the disease varies widely from patient to patient and is unpredictable. About 20% of patients remain asymptomatic or become only mildly symptomatic after an initial clinical event. Another 20% experience a rapidly progressive condition. Most patients, however, will experience some degree of progression.

Women tend to have a better outlook than men. Factors the determine a higher risk for a severe condition include:

Age over 40 years at the time of onset of symptoms
Initial symptoms that affect motor control, mental functioning, or urinary control, or initial symptoms affect multiple regions
Attacks in the first years that are frequent or interval between the first two attacks is short
Incomplete remissions
Rapid progression to disability
MS that is progressive from the beginning or becomes progressive shortly after the onset

Doctors and researchers often use a scale called the Kurtzke Disability Status Scale to assess and predict future disability. The system uses a score of 1 to 10 to rate the degree of walking disability. Experts have used the scale to attempt to predict average times for progression from one stage to the next depending on whether patients have relapsing-remitting or chronic progressive MS.


Score	Disability Description	Relapsing-Remitting MS: Average time until onset of symptoms*	Chronic Progressive MS: Average time until onset of symptoms*
1	No disability and minimal neurologic symptoms.	11.4 years from Score 1 to Score 4	0 years from Score 1 to Score 4
2	Minimal disability in one or two functional areas. Slight weakness or stiffness, mild walking impairment or visual disturbances
3	Moderate disability in one functional area, such as vision or the urinary tract, and possibly more than one minimal disability in several others. Either a part of one of the limbs or a whole side can be partially paralyzed. May stagger at times.
4	Disability is relatively severe but there is full ability to walk without aid. Patients are self-sufficient and can be active 12 hours a day and carry on normal activities. Can walk without aid or rest for 300 to 500 meters.
5	Disability is severe enough to impair or even preclude a full day's activities. Able to walk unaided and without rest for 100 to 200 meters.	23.1 years from Score 1 to Score 6	7.1 years from Score 1 to Score 6
6	Can walk unaided for about 100 meters only with assistance or devices, such as two canes, crutches, or braces.	23.1 years from Score 1 to Score 6	7.1 years from Score 1 to Score 6
7	Mostly restricted to wheelchair, although can manage the wheelchair and leave it unassisted. Can walk with aids no further than about five meters.	33.1 years from Score 1 to Score 7	13.4 years form Score 1 to Score 7
8	Mostly restricted to wheelchair or even bed, but still has effective use of arms remains and able to perform many self-care functions.	(Data not available)	(Data not available)
9	Bedridden. Patient can communicate or eat.
10	Fatality occurs from complications.
* Data taken from Relapses and Progression of Disability in Multiple Sclerosis, The New England Journal of Medicine, November 16, 2000, Vol. 343, No. 20

Because the effects of nerve injury are widespread, complications can be very severe and affect all parts of the body. Although not all patients experience all of the following problems, any of them can negatively impair quality of life.

Fatigue. Fatigue is one of the most common and debilitating MS symptoms and affects at least two-thirds of patients with MS. Fatigue specifically attributed to MS and not to other causes is defined as abnormal fatigue that lasts at least half of the time or more than 6 weeks. It causes a general lack of energy that significantly limits daily functioning regardless of any neurologic symptoms or specific muscle weaknesses. Up to 40% of patients describe fatigue as the most disabling MS symptom, which is higher than weakness, spasticity, motor control, or bowel or urinary problems. Many conditions that are common in MS (sleep disorders, depression, hypersensitivity to sensation, hypothyroidism, medications, heat) may contribute to fatigue. None fully explain the consistent presence or severity of this problem in MS. Researchers using imaging techniques have identified possible changes in part of the brain in MS that may play a role in the fatigue of MS.

Loss of Mobility and Spasticity. Nearly every patient loses some mobility, which may take the form of less or impaired motor control, muscle weakness, impaired balance, and, importantly, spasticity. Spasticity is one of the primary symptoms of MS. It is characterized by weakness, loss of dexterity, and the inability to control specific movements. It is usually more severe in the legs and torso. (Ironically, mild spasticity actually helps improve muscle tone in the legs, which is important in supporting the patient’s weight when walking.) Mobility can be affected by many non-physical factors, including mental well-being, social networks, fatigue, and even the weather.

Pain. About two-thirds of patients experience pain at some point during the course of the disease, and 40% are never pain free. MS causes many pain syndromes; some are acute while others are chronic. Some worsen with age and disease progression. Pain syndromes associated with MS are trigeminal (facial) pain, powerful spasms and cramps, optic neuritis (pain in the eye), pressure pain, stiffened joints, and a variety of sensations, including feelings of itching, burning, and shooting pain.

Bowel Dysfunction. Bowel dysfunction, which can include constipation or fecal incontinence, is a serious problem for many patients. Constipation may be caused by the disorder itself or by medications used to treat spasms or other symptoms.

Sexual Dysfunction. Sexual dysfunction is a common problem, occurring in over 70% of patients. Men are likely to have impotence and women, problems with vaginal lubrication. It appears to be highly associated with urinary dysfunction.

The nerves that branch off the central nervous system (CNS) provide messages to the muscles and organs for normal function. When there is CNS damage, the function of these organs and tissues may be compromised. In multiple sclerosis, the demyelinization of nerve cells may lead to bowel incontinence, bladder problems and sexual dysfunction.

Urinary Dysfunction. Urinary problems from bladder dysfunction occur in two-thirds of patients. Some patients have difficulties in urinating at will, called urinary retention. Often it takes the form of urge incontinence (also called hyperactive or irritable bladder). People with urge incontinence need to urinate frequently or are unable to reach the bathroom before leakage. In such cases, the bladder is overactive. Complications in the urinary tract also produce a high rate of urinary tract infections.

Difficulty Swallowing. A third to a half of patients experience difficulty in chewing or swallowing, problems that may be caused or made worse by many MS medications.

Speech and Hearing Problems. Problems in speech may occur because of difficulty in controlling the quality of the voice and articulating words. (Problems with language itself, however, are very rare in MS.) Hearing problems also occur in MS and may affect speech.

Problems in the Lungs. As the muscles that control breathing weaken, the ability to cough is impaired and the patient is at higher risk for pneumonia and other complications in the lungs.

Osteoporosis. Osteoporosis (loss of bone density) and subsequent fractures are common and under-recognized problems among patients. Osteoporosis is caused and worsened by immobility and by some MS medications. Fractures caused by falls can be far more serious in patients than in the normal population, leading to problems, including deconditioning or even inability to walk, obstruction of the intestines (from pain-relieving medications), and respiratory complications.

Cognitive problems, such as having trouble concentrating and solving problems, affect about half of patients. More people with MS leave work because of such cognitive difficulties than because of physical problems, according to a 2000 study. In about 10% of cases, mental dysfunction may be severe and resemble dementia. The severity of such mental changes appears to be associated with the degree of loss of brain tissue. This offers another argument for early treatment as interferon medications may improve these symptoms.

Between 40 - 60% of patients suffer from depression at some point over the course of the illness, and studies have reported risks for suicide ranging from 3 - 15%. Some evidence suggests that depression in multiple sclerosis is not only due to the social and psychologic impact of MS but also to the disease process itself. Depression may have biologic effects, such as increasing production of inflammatory cytokines, that could exacerbate the disease itself. Doctors should assess patients for depression, even if there are no obvious signs of it. The risk for suicide may be present even in patients who are not obviously depressed. People at highest risk for suicide are those who live alone, those with a history of an emotional disorder (depression, anxiety, alcohol abuse), a family history of mental illness, and people with high social stress.

Diagnosis

Multiple sclerosis is characterized by recurring neurologic episodes that are due to multiple lesions (injured areas) in different locations in the central nervous system. The diagnostic challenges in multiple sclerosis are two-fold:

Making an initial diagnosis as early as possible in order to slow down the disease progression. Most patients first seek medical help after an initial inflammatory event (known as a clinically isolated syndrome) originating from demyelination in the eye, the spinal cord, or the brain. About 30% of these individuals will develop progressive MS within the year. At this time, however, experts cannot predict who among these patients are at highest risk for rapid progression.
Predicting the severity of the disease. Once MS has been diagnosed, the pattern of the disease is uncertain. It can be very benign to rapidly progressive and severe. Magnetic resonance imaging (MRI) is able to detect lesions in the brain indicating MS. But, the severity of the disease does not appear related to the number of lesions, the rate of their appearance, or their location. Researchers are hoping to identify some biologic marker, possibly certain antibodies, that will enable doctors to accurately determine the onset and severity of the problem once a diagnosis has been made.

The McDonald Criteria. There is no single test that can accurately diagnose MS, and a number of other conditions may mimic its symptoms. Some doctors use a set of factors, called the McDonald criteria, for diagnosing multiple sclerosis in early stages. The criteria include the presence of specific symptoms, spinal fluid evaluation, and magnetic resonance imaging techniques for detecting lesions within the central nervous system and tracking them over time. The criteria show high reliability in identifying MS in patients with a variety of disease stages or states, including having only one episode, a typical relapsing-remitting course, or a slow insidious progression without clear attacks or remissions. Depending on the MRI and other findings, the patient is then categorized as having MS, possible MS, or no MS.

The symptoms of MS are similar to a number of other diseases, which must be ruled out. These include stroke, alcoholism, emotional disorders, Lyme disease, chronic fatigue syndrome, fibromyalgia, AIDS, and certain other autoimmune disorders (hypothyroidism, scleroderma, Sjögren syndrome, and systemic lupus erythematosus).

Doctors and investigators generally use a test called the Expanded Disability Status Scale (EDSS) to rate the severity of symptoms. It is also used after a diagnosis to gauge the status of the disease, and score the effectiveness of treatments. The scale ranges from 0 to 10 with higher scores indicating more severe symptoms. These are subjective ratings that require doctor observation skills.

Objections to the use of the EDSS are that it assesses only limp and walking problems and does not assess other important complications, including fatigue, sexual function, and mental function.

No reliable single laboratory procedure or test can establish the diagnosis of multiple sclerosis. Several are necessary before a diagnosis can be made.

Analysis of Cerebrospinal Fluid (CFS). Obtaining a sample of spinal fluid requires a lumbar puncture, or spinal tap. Testing spinal fluid is becoming increasingly important for detecting abnormal proteins, tiny fragments of myelin, or specific white blood cells that can help in making a diagnosis. For example, high levels of the immunoglobulin IgG is useful for making a diagnosis and may be a marker for disease progression. (Immunoglobulins are protein chains that are part of the immune system.)

A lumbar puncture, or spinal tap, is a procedure to collect cerebrospinal fluid to check for the presence of disease or injury. A spinal needle is inserted, usually between the 3rd and 4th lumbar vertebrae in the lower spine. Once the needle is properly positioned in the subarachnoid space (the space between the spinal cord and its covering, the meninges), pressures can be measured and fluid can be collected for testing.

Evoked Potential (EP) Test. This is a simple and painless electrical test of nerve function that assesses how long it takes nerve impulses from the eye, ear, or skin to reach the brain.

Magnetic resonance imaging (MRI) scans are important diagnostic tools in MS and are used for diagnosing multiple sclerosis, tracking changes over time, and helping to determine treatment effectiveness.

Click the icon to see an image of a brain MRI.

Making a Diagnosis and Tracking the Disease. Magnetic resonance imaging (MRI) scans can detect bright patches that indicate injured tissue (lesions) caused by MS. Such lesions may also indicate other conditions, such as infections, migraines, or clots. Importantly, a very sensitive MRI technique using enhancement by a contrast material called gadolinium can indicate recent activity by showing if the blood-brain barrier has been broken down (the first step in the development of MS lesions). Detecting lesions and treating MS early in the disease process may help reduce progression. Many experts therefore now advocate performing a brain MRI as soon as symptoms appear.

Once diagnosed, periodic follow-up MRIs can be used to track the disease and effectiveness of treatments in two ways:

By distinguishing new lesions from old ones
Revealing increasing or decreasing numbers of lesions within the central nervous system over time

Unfortunately, neither the rate nor the number of new or growing lesions necessarily predicts whether symptoms will worsen or if the patient will develop secondary progressive MS.

Measuring Atrophy in Brain and Spinal Cord. As myelin, axons, oligodendrocytes, and neurons are destroyed, the brain begins to shrink. Processing MRI images to determine brain volume may be a useful way to monitor progression and treatment effects. MRI can also detect shrinkage in the spinal cord, which is proving to be a very strong marker of disease progression. A variation of MRI, magnetic resonance spectroscopy (MRS), provides information on the biochemistry of the brain, and may be particularly helpful in detecting this destructive aspect of MS.

Detecting Black Holes.Severe disease progression can be gauged by the presence of so-called "black holes.” These are lesions in the brain that emit very low signals on an MRI scan. Some evidence suggests that they may represent iron deposits in the brain.

Researchers are continuously searching for biologic markers that might help make an accurate diagnosis, predict outcome, or both. Promising markers are antibodies that target two key protein components of myelin: Myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP). If future studies confirm the predictive value of these antibodies, scientists may be able to develop a blood test for MOG and MBP.

Treatment

Patients diagnosed with multiple sclerosis face great uncertainty, since the course of the illness varies so widely among patients. Experts recommend a multidisciplinary approach to the disease, which might involve a neurologist, a nurse or social worker expert in MS, and possibly a specialist in mental health (since depression is so common and the suicide rate is higher than average).

Evidence now strongly suggests that the most destructive changes from multiple sclerosis in the brain occur very early on in the disease process -- and may cause considerable damage even before symptoms begin.

Many experts are now urging treatment after a first episode of relapsing MS (a clinically isolated syndrome) using medication called disease-modifying drugs. They include three interferons -- IFN1b (Betaseron) and IFN1a (Avonex, Rebif) -- and glatiramer (Copaxone). These drugs are all effective and may help slow down or even prevent progression in some patients. Definitive studies comparing them are ongoing.

The best current approach is to use specific findings from advanced MRI techniques to help determine which patients are at highest risk for progression and would be likely candidates for early treatment with disease modifying drugs.

Interferons and other disease-modifying drugs can have significant side effects and are expensive. Furthermore, a significant number of patients have a mild course that can be managed with less toxic drugs. Nevertheless, strong evidence suggests that delaying treatment in most patients increases the risk for severe disability.

Corticosteroids are the standard drugs for treating an acute relapse and hastening recovery. Typically, intravenous methylprednisolone (IVMP) is given once a day for 3 days. Sometimes this is followed by oral prednisolone for a few days.

Disease Modifying Drugs. Since the introduction of disease modifying drugs -- interferons beta (Betaseron) and alpha (Avonex, Rebif) and glatiramer (Copaxone) -- relapsing-remitting multiple sclerosis is now considered a treatable disease. In patients with very active MS, some experts start with Betaseron or Rebif. For patients with possible or probable MS, they begin with Avonex. This drug is slightly less effective than Rebif and Betaseron but has fewer side effects. Copaxone is also a reasonable choice for early mild MS. It appears to have the fewest side effects, longer relapse-free rates than interferons, and its benefits persist for years.

The newest drug, the monoclonal antibody natalizumab (Tysabri), was approved in November 2004 for treatment of relapsing forms of MS. The FDA withdrew it from the market, however, in February 2005 following reports of serious neurological events. In June 2006, the FDA allowed natalizumab back on the market but with special restrictions (see Drug Treatment section).

Other Approaches. Some research has reported benefits from the use of pulsed administration of intravenous methylprednisolone (IVMP) or intravenous immunoglobulin, although there is not enough evidence for either approach to recommend them as first-line choices. Other drugs showing promise include azathioprine (an immunosuppressant) and laquinimod (an oral immune-modulating drug).

Treating Secondary Progressive Multiple Sclerosis (SPMS). Interferons and other standard treatments for relapsing-remitting MS may be helpful for patients with SPMS who are still experiencing relapses. It is not clear if they help those whose condition has become continuously progressive.

Mitoxantrone (Novantrone) was the first drug approved for SPMS. The drug is an immunosuppressant and is proving to delay relapse and progression. Side effects, however, can be serious in some cases. Some experts recommend using mitoxantrone when evidence suggests progression to SPMS, and continuing the interferons Betaseron or Rebif for maintenance.

Other immunosuppressants, such as cyclophosphamide, methotrexate, and cladribine, may help some patients with SPMS. They can have very toxic side effects, however, and there must be clear treatment indications for patients who take these drugs.

Treating Primary Progressive Multiple Sclerosis. No treatments have been proven yet to slow progressive multiple sclerosis. Studies using interferons and glatiramer are under way.

A number of treatments are available for managing symptoms and complications.

Drug Treatment

Corticosteroids (commonly called steroids) are mainstay treatments for acute relapses patients with relapse-remitting MS. High-dose methylprednisolone given intravenously (IVMP) is typically administered for major relapse, often followed by oral prednisone for a few days. Steroids reduce inflammation in the central nervous system and may help suppress the immune system's attack on myelin and even improve electrical conduction.

Steroids, in general, do not improve the long-term course of the disease and can lose effectiveness if overused. They are not generally used for maintenance therapy. Some research, however, is reporting benefits from the use of pulsed administration of intravenous methylprednisolone. Such an approach typically administers the steroid daily for 5 days every 4 months for 3 years, then every 6 months for 2 years. Some research suggests that this approach might reduce destruction in central nervous system, although more evidence is needed before it can be recommended. They can also have considerable adverse effects when used over time.

Side Effects. Side effects of long-term use of steroids include weight gain and facial fullness, hypertension, diabetes, osteoporosis, cataracts, intestinal bleeding, and increased susceptibility to infections. In addition, side effects of steroids on the central nervous system (sleeplessness, memory loss, anxiety, and depression) can be particular problems for patients. It is extremely important to taper withdrawal very carefully after continuously taking steroids for a prolonged period of time. This gives the body time to recover its own ability to produce natural steroids. A serious condition known as adrenal insufficiency can otherwise develop.

Interferons (so-called because they “interfere” with viral replication) both suppress important inflammatory factors in the immune system and have anti-viral properties. Interferons specifically block immune factors known as class II MHC molecules, which are associated with the attack on myelin and the breach in the blood-brain barrier that allows the destructive T cells to pass through.

Specific Interferons Used for MS. Interferon drugs used for MS are IFN1b (Betaseron) and IFN1a (Avonex, Rebif). They are now the treatments of choice for relapsing-remitting MS. Expert organizations urge that they be used early in the course of the disease and continued indefinitely, unless they produce no benefits or have severe side effects.

Successes and Drawbacks. Interferons can reduce flare-ups overall by 30% and have an even greater effect on reducing major relapses. Disease activity, as measured by MRI scanning, is reduced by over 80%. They appear to be about equal in reducing disability. To date, only Avonex has demonstrated slowing progression of mental impairment. It also appears to be better tolerated than other interferons. Studies on their effects on quality of life are limited. None of the interferons are a cure, in any case, and when the drug is discontinued, disease activity may increase. All of these drugs need to be injected. (Oral forms are under investigation.)

Side Effects and Complications. Side effects include:

Pain at the injection site. Many patients taking Betaseron complain of severe pain at the injection site caused by damaged tissue. Experts recommend taking acetaminophen (Tylenol) before the injection and then every 6 hours after each injection for 24 hours during the first 6 months of treatment.
Skin injury at the injection site. Black dead tissue may form around the site, and many patients taking Betaseron have reported severe skin eruptions. These skin injuries heal after the drug is withdrawn, but scarring can occur. This side effect is least severe with Avonex, followed by Rebif.
Other physical side effects. Both drugs cause flu-like symptoms, nausea, vomiting, headaches, and dizziness. Such side effects usually fade after 2 - 3 months.
Depression. Early studies associated taking interferon with a higher risk for depression during the first 2 - 6 months following initial therapy. More recent studies, however, have reported no greater risk for depression in patients taking any of these drugs. MS itself, in any case, is highly associated with depression.
Thyroid abnormalities. Interferon has been associated with autoimmune thyroiditis, a cause of hypothyroidism. Some experts recommend monitoring for thyroid function, particularly in the first year and in those with a history of thyroid problems. If there is no evidence of the condition during that period, the risk for its occurrence appears to be very low.
Liver damage. Interferon may cause liver damage and, in rare cases, liver failure. Patients should avoid alcohol and have regular liver function tests while taking this drug

Neutralizing Antibodies That Reduce Effectiveness. Over time, people taking interferons develop antibodies to the drugs, some of which can neutralize their effects. The risk for neutralizing antibodies (NAbs) increases with higher doses and greater frequency of use. Interferons injected under the skin (Betaseron, Rebif) are more likely to produce neutralizing antibodies than Avonex, which is injected into a muscle. Patients who experience this, however, often can be effectively treated with an alternative interferon or with glatiramer, which has an extremely low risk, for NAbs. In many cases, after switching drugs, NAb levels decline, and the patient may be able to return to the original interferon.

Glatiramer acetate (Copaxone) is a synthetic molecule that resembles a basic protein found in myelin. It is used as a decoy to trick white blood cells into attacking it instead of myelin. It is approved to help reduce the frequency of relapses in patients with relapse-remitting MS. The best results are in patients in early stages, but the longer patients remain on the drug, the greater the improvement. Benefits have persisted for years. Glatiramer acetate can also help reduce the number of new brain lesions.

Glatiramer acetate is also being studied for its effects in patients with primary progressive MS. A 2007 study indicated that while the drug had little benefit for most patients with this type of MS, it may help slow disease progression and delay disability in men with primary progressive MS.

Side Effects. Side effects occur in about 15% of patients, usually right after the injection. They include pain at the injection site, chest pain, rapid heartbeat, flushing, anxiety, and shortness of breath.

Monoclonal antibodies (MAbs) are drugs that target specific antibodies involved with the immune response. In 2004, natalizumab (Tysabri) became the only MAb approved for treatment of MS. Shortly afterwards, reports emerged of progressive multifocal leukoencephalopathy (PML) occurring among patients who took natalizumab for more than 2 years. PML is a rare neurological disease that can affect people with compromised immune systems. Based on these reports, the FDA suspended marketing of natalizumab in February 2005 and recommended that patients discontinue its use.

In June 2006, the FDA allowed natalizumab to return to the market with certain safety restrictions. Doctors can prescribe the drug only to patients who have failed to respond to or who cannot tolerate other MS treatments. Natalizumab can only be taken alone, not in combination with other immune-modifying drugs. Patients who take natalizumab must enroll in a special program called TOUCH, which is run by the drug’s manufacturer. Patients need to get magnetic resonance imaging (MRI) brain scans before they begin taking the drug, and they are evaluated regularly during drug treatment to make sure they are not at risk of developing PML. In the year after these restrictions were implemented, no new cases of PML were reported.

Clinical trials indicate that natalizumab’s benefits may outweigh its risks. Several studies published in 2006 in the New England Journal of Medicine showed that natalizumab, alone or in combination with IFN1a (Avonex) can help prevent disability in patients with multiple sclerosis. Another study suggested that the risk of PML is very low if patients use natalizumab for less than 18 months.

Natalizumab is also being studied for treating complications associated with MS. In a 2007 study, natalizumab helped reduce vision loss in patients with relapsing MS. Vision loss is one of the most common symptoms associated with MS.

Other MAbs under investigation for MS include daclizumab (Zenapax), alemtuzumab (Campath), and rituximab (Rituxan). Results from a 2005 phase II trial for alemtuzumab indicated that the drug helped prevent relapse but also caused serious side effects. Patients who took the drug had a high risk for developing a serious bleeding disorder caused by a low blood platelet count. Daclizumab is currently in phase II trials as is rituximab. Unlike other MAbs, which affect T cells, rituximab targets and depletes B cells. In several studies presented at the 2007 meeting of the American Academy of Neurology, rituximab showed promising results in reducing relapse frequency and number of brain lesions in patients with relapse-remitting MS.

Intravenous immunoglobulin treatments are monthly infusions of natural antibodies. They appear to have some modest benefits for relapsing-remitting MS. Studies suggests that intravenous immunoglobulin reduces relapse rates and occurrences of new lesions and slows disease progression in relapsing-remitting MS. It does not appear to reduce disability. It is extremely expensive and does not appear to have any benefits for patients with secondary progressive MS.

Many drugs being investigated for chronic progressive multiple sclerosis are immunosuppressants, which block certain factors in the immune system that contribute to the inflammatory process. Each of these drugs can produce serious side effects, including susceptibility to infection. Evidence on benefits is uncertain, mainly because of high toxicity or study limitations. Still, some immunosuppressants may help certain patients with severe MS. Among immunosuppressant drugs or procedures that have been investigated with little or no obvious benefits or unacceptably high side effects are total lymphoid irradiation, sulfasalazine, cyclosporine, acyclovir, and oral bovine myelin.

Mitoxantrone. Mitoxantrone (Novantrone) was the first drug approved specifically for secondary progressive MS. Studies suggest that it may help reduce progression and relapse rates. Cumulative doses can have toxic effects on the heart, however, so the drug is only used for a limited period. Mitoxantrone is also being studied in combination with glatiramer acetate. In one preliminary study, initial treatment with mitoxantrone, followed by maintenance treatment with glatirimer acetate, helped reduce relapses for up to 5 years.

Methotrexate. In some patients, low doses of the immunosuppressant methotrexate may slow the course of chronic-progressive MS, particularly in those with secondary progressive MS. To date, studies have found beneficial effects only on the upper body, however. Although this drug, like all immunosuppressants, can have toxic side effects, it may be taken in low doses for MS and so side effects are generally minimal.

Cyclophosphamide. Cyclophosphamide (Cytoxan) blocks cell growth and also suppresses the immune system. Some studies, but not all, have reported benefits for patients with chronic progressive MS. Small studies suggest that monthly intravenous administration or a combination with interferon-beta may help some patients with rapidly deteriorating MS. Cyclophosphamide has many side effects, including hair loss, nausea, vomiting, infertility, lung scarring, and blood abnormalities, and should be used for patients who do not respond to methotrexate.

Azathioprine. Azathioprine (Imuran) is designed to suppress the immune system and reduce the number of cells attacking the CNS myelin. It is used with or without steroids and is sometimes used as an alternative to patients with relapsing-remitting MS who do not respond to either interferon beta or glatiramer acetate. One study reported that 40% of patients had not experienced a relapse after taking the drug for 3 years, although others report only modest benefits. The drug has no effect on progression of disability.

Cladribine. Cladribine (Leustatin) may be effective in delaying progression in patients with chronic progressive MS. It has no significant effect on relapsing-remitting MS.

A number of treatments are under investigation that may prove to be helpful for multiple sclerosis. Those discussed below are only some of them.

Immune-Modulating Drugs. Most MS drugs are injected, but researchers are developing several new drugs that can be taken by mouth. Four of the most promising candidates are cladibrine (Mylinax), fingolimod (FTY720), teriflunomide, and fumarate (BG00012). In late-stage clinical trials, these drugs have shown positive results in the treatment of relapse-remitting MS.

Sex Hormones. Women with MS have a reduced risk of experiencing relapses during pregnancy, probably because of their high levels of the female sex hormones estrogen and progesterone. Because of this association, researchers have investigated whether oral estrogen therapy (estriol) can help prevent relapses. Some small studies have indicated that estriol treatment may help reduce lesions and disease activity, but the overall evidence is still inconclusive. The male sex hormone testosterone is also being studied as a treatment for men with relapse-remitting MS. A small 2007 pilot study suggested that treatment with testosterone gel is safe and may help improve cognitive function, slow brain degeneration, and increase muscle mass.

Cannabinoids. Cannabinoids are compounds in marijuana (cannabis), which may have properties that protect nerve cells. Cannabis has been found to improve pain, mobility, tremor, mood, appetite, fatigue, vision, sexual and urinary function, and memory. In a 2003 study, patients reported less pain and improved mobility (although spasticity itself did not improve). Not all patients respond. The drug may also worsen balance and posture in patients with spasticity. Synthetic versions are being investigated that allow rapid delivery without the unwanted side effects of natural cannabis.

Potassium Channel Blockers. Aminopyridines are potassium-blocking compounds that appear to improve nerve conduction through demyelinated areas. In small, preliminary trials, 4–aminopyridine (also called AP) was associated with mild-to-marked improvement in vision, strength, and coordination and was well tolerated. Beneficial effects, however, lasted only a few hours. A related compound, 3,4–diaminopyridine, or DAP, is being studied for relieving fatigue associated with MS.

Statins. Statins are currently the most important drugs for lowering cholesterol. They are also showing additional possible benefits, including anti-inflammatory and nerve protecting properties, which may help patients with neurologic conditions, including multiple sclerosis.

Plasmapheresis. Plasmapheresis with plasma exchange is a procedure in which blood is removed from the body. Blood cells are separated from plasma (the liquid portion of blood) and mixed with replacement plasma, which is then returned to the body. The replacement plasma is thought to dilute antibodies and other immunologically active substances that may trigger MS. Small studies suggest this procedure may have significant benefits for some patients with severe MS, particularly if they are younger and have an early response to this treatment. Side effects include risk of infection and blood clotting problems.

Stem Cell Transplantation. Investigators are studying the benefits of stem-cell transplantation procedures. Stem cells are produced in the bone marrow and are the early forms for all blood cells in the body (including red, white, and immune cells). Early studies indicate that stem cell transplantation may slow progression, although at this point it is not a cure.

Oligodendrocyte Implants. A newly developed, minimally invasive method to transplant modified oligodendrocyte cells directly into the brain is under investigation. Such cells stimulate nerve and axon growth. If feasible, this approach might be helpful in patients whose MS is not caused by an autoimmune response (where the new cells would be attacked, just as the patient's own cells were).

Other Treatments

Nearly 60% of patients try some form of nontraditional remedies. Research on any benefits is slim, and there may be some danger with many remedies commonly used by patients. The following are a few alternative remedies sometimes used for MS.

Relaxation and Meditation Techniques. Generally harmless, and possibly helpful, nontraditional therapies for MS are relaxation and meditation techniques and Eastern martial art exercises. Such techniques include biofeedback, music therapy, yoga, tai chi, and massage therapy.

Acupuncture. Some patients report benefit from acupuncture, which does carry a very small risk, usually for infection.

Acupuncture, hypnosis, and biofeedback are all alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

Electromagnetic Stimulation. A few centers have studied pulses of weak electromagnetic fields applied to the brain. Very small studies have reported improvement in fatigue, tremors, depression, and other symptoms in patients who were severely affected by MS. In one controlled study, this approach relieved symptoms more effectively than placebo. The effect was small however and more research is needed.

Linoleic Acid. Linoleic acid, commonly known as evening primrose oil, is a polyunsaturated fatty acid believed by some people to be helpful because myelin is composed of fatty acids. No study has proven that it is beneficial, but supplements sold in health food stores do not appear to be harmful.

Oral Enzymes. Oral drugs containing various natural enzymes, including bromelain, trypsin, papain, and rutin, have been used overseas to treat arthritic pain. They appear to reduce inflammation and are also being studied in patients with MS. Such enzymes have been marketed alone and in combinations (Wobenzym, Phlogenzym). In one small study, Phlogenzym was associated with a decline in complications and longer remission. They are not painkillers; any benefits derived from them may take several weeks. As with any natural remedy, there are few clinical studies on these products and no U.S. regulation of quality, safety, or effectiveness.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should check with their doctor before using any herbal remedies or dietary supplements

The following warnings are of particular importance for people with multiple sclerosis:

Antioxidants. Some patients use antioxidant vitamins or supplements (A, E, C, Q10, pycnogenol, OPC, grape seed extract), since the destruction in the MS disease process may be partly due to oxidation (chemical damage from particles called oxygen-free radicals). Theoretically, however, antioxidants can trigger T cells and macrophages (inflammatory components of the immune system) and, therefore, may pose some danger to patients. Small studies to date have not found any worsening of the disease from taking vitamin supplements, but patients should be cautious. No vitamins studied for MS, including carotenoids, vitamin C, vitamin E, B12 injections or vitamin D, have been proven to be beneficial.

Gingko. Although the risks for gingko appear to be low, there is an increased risk for bleeding at high doses. Ginkgo can also interact with high doses of vitamin E, anti-clotting medications, aspirin, and NSAIDs. Large doses have also been known to cause convulsion. Commercial gingko preparations may contain colchicine, a drug that can be harmful in pregnant women and people with kidney or liver problems.

Bee Venom. For years, anecdotal reports have claimed that bee stings relieve some MS symptoms, although a study on mice indicated that it may worsen MS. Bee venom contains many chemicals, some of which can cause severe and sometimes deadly allergic reactions in some people.

Other Remedies. Herbal or natural remedies that supposedly boost the immune system (echinacea, ginseng, garlic, zinc) may worsen MS. Melatonin has been associated with worsening of some autoimmune diseases. Toxic effects have also been reported with herbal remedies such as borage seed oil, chaparral, and comfrey.

Treating the Complications

Fatigue affects at least two-thirds of patients. It is among the most disabling problems in MS and is difficult to treat. Treating any problem (depression, hypothyroidism) that may be causing fatigue is important. Aerobic exercise programs scheduled early in the day have been helpful for patients who can participate. Preventing overheating can improve fatigue.

Modafinil (Provigil, Alertec) is a promising drug that promotes long-lasting wakefulness and is currently used in narcolepsy. Small studies report that it is effective in reducing fatigue and sleepiness, with lower doses (200 mg) being more effective than higher ones. Studies also suggest that the antiviral drug amantadine (Symmetrel) may be helpful.

Managing pain and spasticity in the lower limbs can be difficult. Although many drugs are used to reduce spasticity and lower-limb pain, most studies investigating these drugs have been poorly designed and no treatment has emerged as a front-runner.

Exercise. Mild spasticity actually helps improve muscle tone in the legs, which is important in supporting the patient’s weight when walking. This benefit can be lost with drug treatment. Mild spasticity, then, should be treated with exercises several times a day that improve range of motion.

Drugs Used for Spasticity.

Baclofen (Lioresal) has long been the drug of choice to alleviate more severe spasticity. It is available both orally and infused through an implanted pump. Distressing side effects include confusion, drowsiness, and a rubbery-like sensation in the legs that makes it hard to stand.
Antiseizure medications, such as gabapentin (Neurontin) or levetiracetam (Keppra), may help reduce spasticity without increasing fatigue or impairing concentration. Studies on gabapentin also suggest that it also have other specific benefits for patients, including reducing facial pain and improving vision.
Tizanidine (Zanaflex) is an oral drug that works after one week. In one study, 75% of patients taking tizanidine reported improvement without the leg-muscle weakness experienced using baclofen. The drug does not appear to be any more effective than baclofen, however. Side effects include dizziness, drowsiness, dry mouth, and fatigue. Liver function must be monitored.
Diazepam (Valium) is also used for spasticity and may be particularly useful for patients who also experience anxiety. Drug dependence is the primary problem with diazepam, as well as dizziness, drowsiness, and confusion. The medication should not be used by people who are seriously depressed.
Botulinum toxin (Dysport) injections are being investigated for spasticity in specific regions such as the hip.
Dantrolene (Dantrium) may be an effective alternative for patients who cannot tolerate diazepam or baclofen. Because dantrolene causes muscle weakness, however, it is best suited for either patients who are wheelchair bound but still suffer from spasticity, or for those whose muscles are still strong so that the drug-induced weakness isn't unduly debilitating. It also causes nausea, vomiting, and anorexia, and with high dosages it can cause dangerous liver damage.

Surgery. In very severe cases where medication and exercise are not helpful, surgery may be considered. In such cases, the surgeon cuts the tendons that are involved with spasticity.

Spinal Injections. In very severe cases, administering phenol using spinal injections in the lower back may reduce pain and spasms for some patients with severe conditions. Most patients are not appropriate candidates for this approach.

Other Treatments. Researchers are also investigating non-drug treatments for spasticity. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method that uses a magnet placed on the scalp to generate a magnetic field that stimulates the cortex of the brain. In a small 2007 study, rTMS showed promise in improving lower-limb spasticity in patients with relapse-remitting MS.

Urge Incontinence. Urge incontinence (the need to urinary frequently) is common in patients. To help reduce social difficulties, patients should not drink fluids before going to places where restrooms are not easily available. When possible, they should urinate every 3 - 4 hours. A number of medications are available for urge incontinence, including anticholinergic drugs, such as propantheline bromine (Pro-Banthine), tolterodine (Detrol), or oxybutynin (Ditropan). Sacral nerve stimulation (InterStim) sends electrical pulses to help retrain nerves in the pelvic area, and is also proving to be helpful. Botulinum toxin injection into the urinary tract muscles is being investigated and may be helpful for incontinence caused by spasticity. [See In-Depth Report #50: Urinary incontinence.]

Urinary Retention. Urinary retention occurs in some patients. Sometimes urination can be stimulated simply by pressing the bladder area with the fist or hand, by tapping against it, or by straining. Drugs being tried with some success for this problem are desmopressin (DDAVP), ordinarily used for bed wetting in children, and maprotiline (Ludiomill), an antidepressant. If medication is ineffective, a catheter may be needed, either one used intermittently by the patient or placed in the urinary tract. Various new surgical procedures that reconstruct the bladder or divert urine flow may be effective in severe cases of bladder dysfunction. Because urinary symptoms usually remain intermittent for years, treatment approaches for bladder dysfunction should be limited to medications and other reversible therapies, for as long as possible.

Urinary Tract Infections. Urinary tract infection is common in patients, and a urinalysis should be performed with any symptom flare-ups, fever, or change in bladder symptoms. Treatment uses appropriate antibiotic regimens. Some evidence suggests that cranberry juice may help prevent infections. [See In-Depth Report #36: Urinary tract infection.]

In addition to maintaining a high-fiber diet and drinking plenty of fluids, bulk fiber such as psyllium (Metamucil), with or without a stool softener, may be needed. Going to the bathroom the same time every day, particularly after a meal and waiting there for a movement, reduces the risk of losing control later in the day. Exercise helps patients avoid becoming dependent on laxatives, enemas, or colonic irrigation, which can eventually slow down the bowel and cause imbalances in electrolytes. Biofeedback techniques may be helpful in some patients with limited multiple sclerosis.

Major tremors can be very distressing and are particularly hard to treat. Carbamazepine and glutethimide have some possible benefits, but in general drug therapy has been disappointing. Weight applied to the affected limb has been beneficial in about 20% of cases. Surgery is very controversial.

Trigeminal neuralgia is facial pain, usually on one side, that can be very severe and may be triggered by an event as mild as a breeze or teeth brushing. If nonprescription painkillers fail to alleviate facial pain, it can be treated with anticonvulsive medications. Carbamazepine (Tegretol) is currently the drug of choice. Carbamazepine is also effective on other types of MS pain and spasm-related symptoms, including itching and aching. Another antiseizure drug, gabapentin (Neurontin), however, may be particularly effective for MS. This drug also appears to improve blurred vision associated with MS and may help spasticity in general.

Other drugs used for this symptom include phenytoin (Dilantin), diazepam (Valium), or pimozide (Orap), and the antidepressant amitriptyline (Elavil). If severe pain persists and interferes with function, some patients elect to have a section of a nerve surgically removed or blocked. This relieves pain but causes numbness. Before patients commit to such a procedure, they should ask the doctor to temporarily block the nerve with an anesthetic in order to experience the effect of numbness before undergoing irreversible surgery.

A small percentage of patients suffer from pseudobulbar affect (uncontrollable laughing or crying). Neurodex is an investigative drug that is showing promise in controlling these symptoms. The drug combines dextromethorphan (an ingredient contained in many cough suppressants) and the enzyme inhibitor quinidine.

Sildenafil (Viagra) may help improve sexual dysfunction in some patients. Corticosteroids, which are sometimes used for other MS symptoms, also improve sexual function. Other treatments are available that might be very beneficial. Patients should not be shy about discussing sexuality with their doctor. [See In-Depth Report # 15: Erectile dysfunction.]

Techniques for helping patients with swallowing problems include using specific head and tongue positions to assist swallowing, and preparing pureed food. Patients may need to work with otolaryngologists (doctors specializing in ear, nose, and throat disorders) to address swallowing problems. Left untreated, swallowing problems can increase a patient's risk of aspiration pneumonia, malnutrition, dehydration, and other problems.

MS is a strong risk factor for osteoporosis. In addition to calcium and vitamin D supplements, a number of drugs are now available to help prevent bone loss and reduce the risk of fractures due to osteoporosis. [See In-Depth Report #18: Osteoporosis.]

Treating Depression. Treating depression may not only improve mood but may also have direct benefits for patients.

Antidepressants known as tricyclics may have specific benefits for MS in addition to managing severe depression. Amitriptyline (Elavil), for example, may be effective in alleviating the extreme mood swings that frequently occur in patients. This “emotional incontinence,” the inability to control emotions, can distress some patients more than physical symptoms. Other tricyclics include desipramine (Norpramin, Pertofrane) and imipramine (Tofranil), which have additional effects that improve bladder symptoms in some patients. These drugs, however, can have severe side effects.
Newer antidepressant drugs, known as SSRIs (serotonin-reuptake inhibitors), which include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil), may be better tolerated. A study on sertraline suggested that it may also reduce the immune system's inflammatory response.

Stress Reduction and Supportive Measures. Stress can worsen symptoms, and may worsen the disease itself. Reducing stress is an important part of general health maintenance. Studies on methods for reducing stress report improved well-being in patients. A sense of control and connection appears to be extremely important for patients. Relaxation or meditation exercises can be beneficial, although cognitive-behavioral methods may be more effective in these patients. [See In-DepthReport # 31: Stress.]

Support for Caregivers. Many patients require long-term physical, financial, and psychological support from family and friends. The physical and mental health of the caregiver are critical. In one study, caregivers reported that among the most distressing aspects were the psychological impact of MS on the patient and the incurability of the disease. Most caregivers identified the best form of support to be practical help, cooking, cleaning, and better availability of medical and financial advice. Therapeutic help for family members may also be helpful.

Interferon, used to treat MS, may improve mental function. Other medications and therapies may also be helpful. For example, drugs called cholinesterase inhibitors, such as donepezil (Aricept), which are used for Alzheimer's disease, may help improve mental functioning. Vocational programs for the patient may also be helpful. Therapeutic programs for both patients and their families can help them better understand and cope with cognitive weaknesses such as concentration and problem solving.

Lifestyle Changes

People with multiple sclerosis should make every effort to preserve their general health. A healthy diet, sufficient rest, establishing priorities to conserve energy, and developing emotional support networks can all be very helpful.

Some dietary suggestions for patients with MS include:

Drink two quarts of water a day and avoid caffeine-containing beverages, which are actually dehydrating. This helps avoid constipation (although may cause difficulties in patients who also have urge incontinence).
Eat a diet rich in fiber, particularly from whole grains (especially bran, oats, or flax), fruits (particularly prunes), and vegetables.
Low-fat diets have not proven to have much effect on MS but are, in any case, generally healthy.
Fish and fish oil. Omega-3 fatty acids, which are found in oily fish, have been associated with protection against inflammation and some reduction in symptoms in people with various autoimmune conditions. Such fatty acids are also available in supplements as docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids. Standards for optimal amounts and forms of omega-3 fatty acids have not yet been established, however. Some experts recommend that people with MS eat three fish meals a week.

Special diets, such as those that are gluten- or yeast-free, have not shown to have any direct effect on the symptoms or course of MS.

Exercise is an important component in managing MS. An active patient with MS is less likely to develop certain complications, such as bladder and bowel dysfunction, osteoporosis, permanent muscle contractions, ulcerations of the skin, or abnormal blood clotting. MS symptoms can temporarily worsen during physical activity, however, so any program must be planned carefully. A health professional should be consulted to determine the best form of physical activity. One study reported that physical rehabilitation for 3 weeks in a hospital setting was significantly more effective in achieving functional independence than home exercise. It is not known if the same benefits can be achieved with a similar program outside the hospital.

Some suggestions include:

Exercise programs must be designed to stimulate working muscles, but at the same time avoid overload and overheating, which can block nerve conduction.
Stretching and range-of-motion exercises are important because they can relieve muscle spasticity.
Pool exercises are particularly helpful. Water supports the body, and cool water dissipates heat.
Specific exercises that strengthen and increase the endurance of muscles that control breathing functions may be helpful. However, it is unclear if such exercises reduce lung complications over the long-term.
Gradually, patients may be able to build up to more complex exercise programs.

Body overheating causes demyelinated nerves to function less efficiently than usual. Although this effect is resolved within a few hours of regaining normal body temperature, active cooling can help reduce fatigue and improve stability. As a result, researchers are studying the effectiveness of cooling suits.

The following measures may be helpful:

Use air conditioners in the summer.
Keep the home slightly cool in winter.
Avoid swimming in heated pools.
A portable helmet that uses cold liquid to cool the head and neck and therefore lower core body temperatures may help MS symptoms during daily activities.

MS symptoms worsen during a cold or the flu, probably because of increased immune system activity. Experts recommend that patients with MS receive a flu shot in the fall. However, experts warn that patients should not take the nasal spray version of the flu vaccine (FluMist Intranasal). Unlike the flu injection vaccine, which uses an inactivated virus, FluMist contains a live virus. Live virus vaccinations may be harmful for people with MS, especially those who take immune-suppressing drugs.

Resources

www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.aan.com -- American Academy of Neurology
www.msaa.com -- Multiple Sclerosis Association of America
www.nmss.org -- National Multiple Sclerosis Society
www.msfacts.org -- Multiple Sclerosis Foundation
www.www.fda.gov/cder/drug/infopage/natalizumab -- FDA information on natalizumab (Tysabri)
www.myelin.org -- The Myelin Project
www.abledata.com -- National database of assistive devices and rehabilitation equipment

References

Balcer LJ, Galetta SL, Calabresi PA, Confavreux C, Giovannoni G, Havrdova E, et al. Natalizumab reduces visual loss in patients with relapsing multiple sclerosis. Neurology. 2007 Apr 17;68(16):1299-304.

Boggild M. .Rationale and experience with combination therapies in multiple sclerosis. J Neurol. 2006 Nov;253 Suppl 6:vi45-vi51.

Centonze D, Koch G, Versace V, Mori F, Rossi S, Brusa L, et al. Repetitive transcranial magnetic stimulation of the motor cortex ameliorates spasticity in multiple sclerosis. Neurology. 2007 Mar 27;68(13):1045-50.

Correale J, Fiol M, Gilmore W. The risk of relapses in multiple sclerosis during systemic infections. Neurology. 2006 Aug 22;67(4):652-9. Epub 2006 Jul 26.

Hensiek AE, Seaman SR, Barcellos LF, Oturai A, Eraksoi M, Cocco E, et al. Familial effects on the clinical course of multiple sclerosis. Neurology. 2007 Jan 30;68(5):376-83.

Kappos L, Antel J, Comi G, Montalban X, O'Connor P, Polman CH, et al. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med. 2006 Sep 14;355(11):1124-40.

Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006 Dec 20;296(23):2832-8.

Sicotte NL, Giesser BS, Tandon V, Klutch R, Steiner B, Drain AE, et al. Testosterone treatment in multiple sclerosis: a pilot study. Arch Neurol. 2007 May;64:683-688.

Wolinsky JS, Narayana PA, O'Connor P, Coyle PK, Ford C, Johnson K, et al. Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol. 2007 Jan;61(1):14-24.

Review Date:
5/26/2007
Reviewed By:
Harvey Simon, M.D., Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

A.D.A.M. Copyright

adam.com

Epilepsy

FitSugar — Wed, 08 Oct 2008 17:35:12 -0700

In This Report

Highlights
Introduction
Causes
Outlook and Effects
Diagnosis
Treatment
Treatment After The First S...
Medications
Surgery
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the Food and Drug Administration (FDA) approved levetiracetam (Keppra) for treatment of primary generalized tonic-clonic seizures in adults, and children ages 6 years and older, who have idiopathic generalized epilepsy. Levetiracetam was previously approved for partial-onset seizures and myoclonic seizures.

Carbamazepine and Genetic Testing

In 2007, the FDA recommended that patients of Asian ancestry get a genetic test prior to taking carbamazepine (Tegetrol, Equetro, Carbatrol). Rare, but serious, side effects of carbamazepine include life-threatening skin reactions such as Stevens-Johnson syndrome. The risk for these skin reactions is significantly higher for patients of Asian ancestry. A simple blood test can check for the presence of a genetic mutation that increases this risk. Patients who test positive for this gene should not take carbamazepine unless the benefits clearly outweigh the risks.

Epilepsy and Suicide Risk

People with epilepsy have a high risk for suicide, especially within 6 months of diagnosis, suggests a 2007 study in Lancet Neurology. The researchers found that suicide risk was especially high for people who have both epilepsy and another psychiatric condition (such as depression, anxiety, schizophrenia, or alcoholism). The researchers recommend that doctors carefully monitor newly diagnosed patients.

Ketogenic Diet

The ketogenic diet, which is characterized by high fat and low carbohydrate intake, is resurging in popularity for the treatment of children with difficult-to-control seizures, according to a 2007 review in Pediatrics. The ketogenic diet helps stop or reduce seizures in about a third of children. The diet is complex. Parents should seek supervision and guidance from a doctor or trained health professional.

Introduction

Epilepsy is characterized by unprovoked, recurring seizures that disrupt the nervous system and can cause mental and physical dysfunction. In the U.S., about 2.5 million people are affected by epilepsy and seizures. About 10% of the American population will experience at least one seizure during their lifetime.

The structures of the brain include: the brainstem, consisting of the spinal cord, the medulla oblongata, the pons and the midbrain; the cerebellum; the cerebrum (one half, or hemisphere shown); and the diencephalon.

Epilepsy affects all age groups. Males have a slightly higher risk than females. The incidence is highest in children, with another, but lesser, peak occurring after age 60. According to one estimate, 14% of epilepsy patients are under 15 years old, and about 25% are over age 64.

Every year, 25,000 - 40,000 American children have a first seizure that is unrelated to a fever. Epilepsy is decreasing in childhood but increasing in the elderly, probably because of mild strokes and cardiac arrest.

Epilepsy is not a single disorder but rather a wide spectrum of problems. What all types of epilepsy share are recurrent, unprovoked seizures caused by an uncontrolled electrical discharge from nerve cells in the cerebral cortex. This part of the brain controls higher mental functions, general movement, and the functions of the internal organs in the abdominal cavity, perception, and behavioral reactions.

Seizures are a symptom of epilepsy. Epilepsy types are generally put into two categories, which are based on the specific biologic mechanisms involved in the seizure and the anatomical location of the seizure. The two types are:

Partial (also called focal or localized) seizures. These seizures are more common than generalized seizures and occur in one or more specific locations in the brain. In some cases, partial seizures can spread to wide regions of the brain. They are likely to develop from specific injuries, but in most cases the exact origins are unknown.
Generalized seizures. These seizures typically occur in both sides of the brain. Many forms of these seizures are genetically based. There is usually normal neurologic function.

Experts are finding, however, that these categories do not actually reflect what is now known about the brain's anatomy. For example, the words "partial" and "generalized" suggest that seizures either involve only part of the brain or are widespread. However, a number of events in the brain occur with either type, muddying these distinctions. Researchers are now in the process of making clearer definitions and terms that reflect what actually is happening in the brain.

New classification systems better define specific epilepsies. Some professional groups now suggest that epilepsies be classified in the following five ways:

Type of seizure (partial or generalized)
Description of the seizure onset and evolution
Specific syndromes that are associated with one or more seizure types (however, not all seizures will be part of a syndrome)
Specific causes of the seizures, if known
Degree of impairment

These seizures are subcategorized as "simple" or "complex partial."

Simple Partial Seizures. A person with a simple partial seizure (sometimes known as Jacksonian epilepsy) does not lose consciousness, but may experience confusion, jerking movements, tingling, or odd mental and emotional events. Such events may include deja vu, mild hallucinations, or extreme responses to smell and taste. After the seizure, the patient usually has temporary weakness in certain muscles.
Complex Partial Seizures. Slightly over half of seizures in adults are complex partial type. About 80% of these seizures originate in the temporal lobe, the part of the brain located close to the ear. Disturbances there can result in loss of judgment, involuntary or uncontrolled behavior, or even loss of consciousness. They may lose consciousness briefly and appear to others as motionless with a vacant stare. Emotions can be exaggerated; some sufferers even appear to be drunk. After a few seconds, a patient may begin to perform repetitive movements, such as chewing or smacking of lips. Episodes usually last no more than 2 minutes. They may occur infrequently, or as often as every day. A throbbing headache may follow a complex partial seizure.

In some cases, simple or complex partial seizures evolve into what are known as secondarily generalized seizures. The progress may be so rapid that the partial stage is not even noticed.

While the term "partial" implies the seizures affect only small or specific brain locations, in reality, they almost always involve diffuse and even widespread areas. In the future, the term "focal seizures" will most likely replace the term "partial seizures," and its subcategories. Until new classifications are more widely in use, this report will continue to use the term "partial seizures" and its subcategories.

Generalized seizures are caused by nerve cell disturbances that occur in more widespread areas of the brain than do partial seizures. Therefore, they have a more serious effect on the patient. They are further subcategorized as tonic-clonic (or grand mal) or absence (petit mal) seizures.

Tonic-Clonic (Grand Mal) Seizures. The first stage of a grand mal seizure is called the tonic phase, in which the muscles suddenly contract, causing the patient to fall and lie stiffly for about 10 - 30 seconds. Some people experience a premonition or aura before a grand mal seizure. Most, however, lose consciousness without warning. If the throat or larynx is affected, there may be a high-pitched musical sound (stridor) when the patient inhales. Spasms occur for about 30 seconds to 1 minute. Then the seizure enters the second phase, called the clonic phase. The muscles begin to alternate between relaxation and rigidity. After this phase, the patient may lose bowel or urinary control. The seizure usually lasts a total of 2 - 3 minutes, after which the patient remains unconscious for a while and then awakens to confusion and extreme fatigue. A severe throbbing headache similar to migraine may also follow the tonic-clonic phases.
Absence (Petit Mal) Seizures. Absence or petit mal seizures are brief losses of consciousness that occur for 3 - 30 seconds. Physical movement and loss of attention may stop for only a moment. Such seizures may pass unnoticed by others. Small children may simply appear to be staring or walking distractedly. Petit mal may be confused with simple or complex partial seizures, or even with attention deficit disorder. [See In-Depth Report #30: Attention deficit hyperactivity disorder.] In petit mal, however, a person may experience attacks as often as 50 - 100 times a day. About 25% of patients with petit mal develop grand mal seizures. An electroencephalogram (EEG) test that shows a specific brain wave pattern can usually identify these patients.

Click the icon to see a depiction of a tonic-clonic seizure.

Atonic (Akinetic) Seizures. A person who has an atonic (or akinetic) seizure loses muscle tone. Sometimes it may affect only one part of the body so that, for instance, the jaw slackens and the head drops. At other times, the whole body may lose muscle tone, and the person can suddenly fall. A brief atonic episode is known as a drop attack.

Simply Tonic or Clonic Seizures. Seizures can also be simply tonic or clonic. In tonic seizures, the muscles contract and consciousness is altered for about 10 seconds, but the seizures do not progress to the clonic or jerking phase. Clonic seizures, which are very rare, occur primarily in young children, who experience spasms of the muscles but not tonic rigidity.

Myoclonic. Myoclonic seizures are a series of brief jerky contractions of specific muscle groups, such as the face or trunk.

Epilepsy is also grouped according to a set of common characteristics, including:

Patient age
Type of seizure or seizures
Whether a cause is known or not (idiopathic)

A few syndromes and inherited epilepsies are listed as follows. They do not represent all epilepsies.

West Syndrome (Infantile Spasms). West syndrome, also called infantile spasms, is a disorder that involves spasms and developmental delay in children within the first year, usually in infants ages 4 - 8 months.

Benign Familial Neonatal Convulsions. Benign familial neonatal convulsions (BFNC) are a rare, inherited form of generalized seizures that occur in infancy. BFNC appears to be caused by genetic defects that affect ion channels in nerve cells that carry potassium.

Juvenile Myoclonic Epilepsy (Impulsive Petit Mal). Juvenile myoclonic epilepsy, also called impulsive petit mal epilepsy, is characterized by generalized seizures, usually tonic-clonic marked by jerky movements (called myoclonic jerks), and sometimes absence seizures. This accounts for 7% of epilepsies, and usually occurs in individuals ages 8 - 20.

Adult Myoclonic Epilepsy. Some research suggests that adult myoclonic epilepsy may be a previously un-described and distinct syndrome. It involves the development of generalized epilepsy of unknown causes in middle-aged adults.

Lennox-Gastaut Syndrome. Lennox-Gastaut syndrome is a severe form of epilepsy in young children that causes multiple seizures and some developmental retardation. It usually involves absence, tonic, and partial seizures.

Myoclonic-Astatic Epilepsy. Myoclonic-astatic epilepsy (MAE) is a combination of myoclonic seizures and astasia (a decrease or loss of muscular coordination), often resulting in the inability to sit or stand without aid.

Progressive Myoclonic Epilepsy. Progressive myoclonic epilepsy is an inherited disorder occurring in children ages 6 - 15. It usually involves tonic-clonic seizures and marked sensitivity to light flashes. Although the disease was previously considered to be progressive throughout life, current therapies have significantly improved its outlook.

Autosomal Dominant Nocturnal Frontal Lobe Epilepsy. Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a rare, inherited syndrome that usually occurs during childhood, typically around age 11. However, onset varies widely within families. Seizures can be dystonic (twisting contractions) or tonic (muscle contractions), or involve thrashing. They are brief, frequent, and occur in clusters during the night. The seizures often subside with age. ADNFLE appears to be caused by an alteration in the brain receptor neuronal nicotinic acetylcholine,

Landau-Kleffner Syndrome. Landau-Kleffner syndrome is an epileptic condition that results in the inability to communicate either with speech or by writing (aphasia).

Contactin-Associated Protein-Like 2 (CASPR2) Epilepsy. CASPR2 is associated with a childhood epilepsy and autism disorder found in closely related relatives in Amish communities.

Status epilepticus (SE) is a serious, potentially life-threatening, condition that can lead to chronic epilepsy. It occurs in 100,000 - 150,000 people in the U.S. each year, over half of whom are children. Permanent brain damage or death can result if the seizure is not treated effectively.

The condition is defined as recurrent convulsions that last for more than 20 minutes and are interrupted by only brief periods of partial relief. Although any type of seizure can be sustained or recurrent, the most serious form of status epilepticus is the generalized convulsive or tonic-clonic type. In more than a third of cases, status epilepticus occurs with the first seizure. The trigger is often unknown, but can include the following:

Failure to take anti-epileptic medications (accounts for about a third of status epilepticus events)
Abrupt withdrawal of certain anti-epileptic drugs, particularly barbiturates and benzodiazepines
High fever
Poisoning
Electrolyte imbalances (imbalance in calcium, sodium, and potassium)
Cardiac arrest
Stroke. In one study, about 9% of stroke patients with seizures had status epilepticus, which resulted in higher disability after the stroke, particularly if these severe seizures occurred within a week of the stroke
Low blood sugar in people with diabetes
Central nervous system infection
Brain tumor
Alcohol withdrawal

Causes

The cause of a seizure is determined in about 28% of partial epilepsy patients. In the rest, however, epilepsy is deemed idiopathic, which means that the cause is unknown. The age of seizure onset can sometimes offer a clue. Idiopathic epilepsy is rare in children and young adults.

Epileptic seizures are triggered by abnormalities in the brain that cause a group of nerve cells in the cerebral cortex to become activated simultaneously, emitting sudden and excessive bursts of electrical energy. A seizure's effect depends on the location in the brain where this electrical hyperactivity occurs. Effects range from brief moments of confusion to minor spasms to loss of consciousness.

Click the icon to see an animation about the nervous system.

Ion Channels. Sodium, potassium, and calcium act as ions in the brain. They produce electric charges that must fire regularly in order for a steady current to pass from one nerve cell in the brain to another. If the ion channels that carry them are genetically damaged, a chemical imbalance occurs. This can cause nerve signals to misfire, leading to seizures. Abnormalities in the ion channels are believed to be responsible for absence and many other generalized seizures.

Neurotransmitters. Abnormalities may occur in neurotransmitters, the chemicals that act as messengers between nerve cells. Three neurotransmitters are of particular interest:

Gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing.
Serotonin's role in epilepsy is also being studied. Serotonin is a brain chemical that is important for well-being and associated behaviors (eating, relaxation, sleep). Imbalances in serotonin are also associated with depression.
Acetylcholine is a neurotransmitter that is important for learning and memory.

Dozens of genetic syndromes representing a variety of seizure patterns may account for the different forms epilepsy.

A genetic cause has been identified for at least some cases of juvenile myoclonic epilepsy, which represents 10% of all epilepsy cases. (Such research and other studies have pointed to the GABA signaling system as an important player in many cases of epilepsy.)

Febrile seizures are caused by high fever. They usually occur in children ages 3 months to 5 years. Between 10 - 15% of children with epilepsy have a history of febrile seizures before they develop epilepsy. However, febrile seizures are quite common and occur in about 3% of all children under 5 years old. Nearly all are brief and have no long-lasting effect.

In young children, high fever from a vaccination can, in rare instances, trigger seizures. These seizures are almost always temporary and have no serious consequences.

Some controversy arose a few years ago over the possibility that the DTP (diphtheria-tetanus-pertussis) vaccine might trigger epilepsy or other neurologic diseases. Some experts suggest that children who have neurologic events following their DTP shot already have a preexisting impairment such as epilepsy, which is revealed, but not caused by, the vaccine. Children with existing epilepsy may be at risk for seizures 2 or 3 days after the vaccination. Infants with suspected neurologic problems may have their vaccinations delayed until their neurologic situation is clarified, but not beyond their first birthday. Also, a newer version of the DTP vaccine does not contain a live virus and so reduces the risk of any seizure.

Brain Tumors. Both cancerous and noncancerous brain tumors can cause seizures in all patients.

Hydrocephalus and Shunts. Hydrocephalus occurs when cerebrospinal fluid (CSF) accumulates in the brain, leading to excessive swelling of the brain ventricles. The resulting pressure can damage the brain's tissue. Hydrocephalus itself is not commonly known to cause seizures, but its treatment, which involves insertion of a shunt, may cause them. The shunt is a device that drains the excess fluid from the brain. Up to half of children who receive shunts may experience epileptic seizures, particularly if the shunt is placed before 2 years of age. More research on its relationship to epileptic seizures is needed.

Focal Cortical Dysplasia. This is an abnormality in fetal development in which the normal migration of nerve cells is altered. It can cause very severe epilepsy that is difficult to treat.

Hippocampal Sclerosis. Hardened tissue (sclerosis) in the brain's hippocampus is the most commonly identified abnormality in patients with partial epilepsy. Such abnormal brain tissue leads to structural reorganization, and both the loss and regeneration of nerve cells.

Cavernous Angiomas. Cavernous angiomas are blood vessels that grow abnormally and, like a tumor, can put pressure on nerve tissue.

Other Causes of Seizures in Children. Seizures in infants and children may be due to birth defects, difficulties during delivery, or poisoning.

Alcohol Abuse. Alcohol abuse is one of the most common causes of adolescent- and adult-onset seizures. Seizures, nearly always generalized tonic-clonic, occur in about 10% of adults during withdrawal. Multiple seizures happen in about 60% of these patients. The first seizure occurs 7 hours to 2 days after the last drink, and the time between the first and last seizure is usually 6 hours or less. [For more information, see In-Depth Report #56: Alcoholism.]

Sudden withdrawal from certain antianxiety or antidepressant drugs such as benzodiazepines, barbiturates, and tricyclic antidepressants can also contribute to seizures.

Head Injuries in Adults. Head injuries to adults can cause seizures, with the risk highest in severe head trauma. A first seizure related to the injury can occur years later, but only very rarely. People with mild head injuries, which involve loss of consciousness for fewer than 30 minutes, have only a slight risk that lasts up to 5 years after the injury.

Head Injuries in Infants and Children. Infants are at high risk for head trauma, and the severity of injury may be difficult to determine. The risk of even one seizure is generally only a concern after severe head trauma. Most children who have had a minor or not very serious head injury do not need to have medications to prevent seizures, especially when an evaluation in the emergency department was unnecessary.

Stroke. Seizure is a symptom of a major stroke. Even injury to the brain from small strokes may cause seizures. Patients who have had a severe stroke are 5 times more likely to develop epilepsy than patients who have had a mild stroke.

Seizures in adults can also be caused by:

Low blood sugar (hypoglycemia), a complication of diabetes in both children and adults.
Medications such as theophylline, meperidine, tricyclic antidepressants, phenothiazines, lidocaine, quinolones, penicillins, selective serotonin re-uptake inhibitors, isoniazid, antihistamines, cyclosporine, interferons, cocaine, lithium, amphetamines, and alcohol (withdrawal).
Occupational exposure to environmental triggers. High exposure to certain chemicals has been linked with seizures.
Alzheimer's or other degenerative brain diseases in the elderly.
Infections of the brain and central nervous system such encephalitis and meningitis.

The organs of the central nervous system (brain and spinal cord) are covered by three connective tissue layers called the meninges. They consist of the pia mater (closest to the CNS structures), the arachnoid, and the dura mater (farthest from the CNS). The meninges help support blood vessels and contain cerebrospinal fluid. The structures are involved in meningitis, an inflammation of the meninges, which, if severe, may become encephalitis, an inflammation of the brain.

Between 20 - 45% of cases of untreatable seizures have a psychologic rather than physical origin. In this form of epilepsy, known as pseudoepilepsy or psychogenic epilepsy, the patient has no conscious intent of forcing a seizure and does not show unusual emotional behavior or signs of hysteria. It is very difficult to treat and can be very disabling. Pseudoepilepsy can usually be distinguished from true epilepsy using an electroencephalogram (EEG), which measures brain waves. The cause of pseudoepilepsy is unknown.

Outlook and Effects

Most patients can control their seizures with a single drug and stop drug treatment completely after 2 years without seizures. In fact, patients who respond well to an anti-epileptic drug (AED), have a better chance for remaining seizure-free in the future. In general, patients who do not have good control with medications are more likely to have difficulty with epilepsy treatment.

Injuries from Falls. Because many people with seizures fall, injuries are common. Although such injuries are usually minor, people with epilepsy have a higher incidence of fractures than those without the disorder. Epilepsy patients who take the drug phenytoin have an even higher risk, since the drug can cause osteoporosis.

Household Accidents. According to a 2006 study, the kitchen and bathroom are two of the most dangerous places for children with epilepsy. Parents should take precautions to prevent burning accidents from stoves and other heat sources. Children with epilepsy should never be left alone when bathing.

Driving and the Risk for Accidents. Being unable to drive is an extremely distressing and severe component of epilepsy. Drivers with well-controlled epilepsy are not at a high or unacceptable risk for automobile accidents. Uncontrolled epilepsy, however, poses a high risk. Needless to say, seizures can be very dangerous if they occur while a person is driving. Studies have reported that more than a fourth of drivers with uncontrolled epilepsy had a seizure-related accident at some time. Many of these accidents resulted in injuries to the patient or others.

Certain factors can help predict who may safely drive:

A long duration between seizures. In one study, being seizure-free for 6 months reduced the risk for accidents by 85%, and being seizure-free for 1 year lowered the risk by 93%. State laws restricting driving in people with seizures vary from requiring seizure-free periods of 3 months (which is too short for protection) to 18 months.
Having few seizure-related accidents.
Having a reliable pre-seizure warning sign, such as an aura.

Accidents while Swimming. Swimming poses another danger for people with epilepsy, particularly those with tonic seizures, which can cause the diaphragm to expel air quite suddenly. People with epilepsy who swim should avoid deep and cloudy water (a clear swimming pool is best), and always swim with a knowledgeable, competent, and experienced companion or have a supervisor on site.

Epileptic patients who are cured have a normal lifespan. Their long-term survival rates are lower than average if medications or surgery fail to stop the seizures. The lower survival rate is partly due to a higher-than-average risk for death due to accidents and suicide. The specific cause of the seizure may also contribute to fatalities.

There is a very low risk for sudden death in patients with epilepsy. Although the causes of such events are not fully known, experts suspect heart arrhythmias in many cases.

Long-Term General Effects. In general, the long-term effects of seizures vary widely depending on the seizure's cause. The long-term outlook for children with idiopathic epilepsy (epilepsy of unknown causes) is very favorable. One study reported that 68 - 92% of these patients were seizure-free after 20 years. Another study reported that they had a survival rate no different from children without these seizures.

Children whose epilepsy is a result of a specific condition (for example, a head injury or neurologic disorder) have higher mortality rates than the normal population, but their lower survival rates are most often due to the underlying condition, not the epilepsy itself.

Effect on Memory and Learning. The studies on the effects of seizures on memory and learning vary widely and depend on many factors. In general, the earlier a child has seizures and the more extensive the area of the brain affected, the poorer the outcome. Children with seizures that are not well-controlled are at higher risk for intellectual decline.

Social and Behavioral Consequences. Learning and language problems, and emotional and behavioral disorders, occur in a significant number of children with several of the partial epilepsy syndromes. These children perform worse on behavioral tests than do other children. Whether these problems are caused by the seizure disorder and anti-seizure medications or are simply part of the seizure disorder remains unclear.

Effect on Mental Functioning in Adults. The effects of adult epilepsy on mental functioning are not clear. More research is needed in this area, as results have been contradictory.

Psychological Health. About 25 - 75% of adults with epilepsy show signs of depression. People with epilepsy have a high risk for suicide, particularly in the first 6 months following diagnosis. The risk for suicide is highest among people who have epilepsy and an accompanying psychiatric condition such as depression, anxiety disorder, schizophrenia, or chronic alcohol use.

Overall Health. Many patients with epilepsy describe their overall health as "fair" or "poor," compared to those who do not have epilepsy. People with epilepsy also report a higher frequency of pain, depression, anxiety, and sleep problems. In fact, their overall health state is comparable to people with other chronic diseases, including arthritis, heart problems, diabetes, and cancer. Treatments can cause considerable physical effects, such as osteoporosis and weight changes.

Effects on Sexual Function. There have been studies suggesting that up to two-thirds of patients with epilepsy experience sexual disturbances, including impotence in men. Causes of these problems may be emotional, medication induced, or a result of changes in hormone levels:

Epilepsy in childhood may cause disturbances in hormones regulating puberty.
Persistent seizures in adults may be associated with other hormonal and neurologic changes that contribute to sexual dysfunction.
Negative emotions due to epilepsy can reduce sexual drive.
Medications may be responsible for many of these cases, although newer drugs may reduce this problem.

Studies have been conflicting on the effects of fertility from epilepsy, but most suggest that fertility rates among women with epilepsy are lower than among women in the general population. A number of factors, including anti-epileptic drugs (AEDs) or social factors such as marriage at an older age, may contribute to this lower rate. Certain AEDs, particularly valproate, disrupt ovulation and menstruation by increasing male hormone levels and weight and causing polycystic ovaries.

Preparing to Become Pregnant. A woman should visit her doctor at least 3 months before becoming pregnant to talk about risks of medications and the possibility of making any changes.

A woman who has been seizure-free for 2 or more years may attempt to discontinue drugs under her doctor’s supervision.
If she has not been seizure-free, she should continue medications but try to reduce them to a single drug, if possible. (Again, under a doctor’s supervision.)
If a woman taking antiseizure medications has an unplanned pregnancy, there may be no point in switching medications right away, since the effects of the drugs last for 10 weeks. However, she should notify her doctor immediately.
Folic acid is recommended for all pregnant women, and women with epilepsy should talk with their doctor about taking a supplement of folic acid (5 mg) at least 3 months before conception as well as during the first trimester.

Effect of Pregnancy on Seizure Frequency. The frequency and intensity of seizures vary widely in women with epilepsy. About 25% of pregnant women with epilepsy face an increase in events, and the risk is highest in those who have more than one seizure per month prior to becoming pregnant. In most cases, however, there is no change at all. Some pregnant women even have a decrease in seizures. The risk is lower in women who experience less than one seizure in the 9 months prior to becoming pregnant.

The following conditions may contribute to an increase in seizures during pregnancy:

Nausea and vomiting (vitamin B6 and antihistamines may help with nausea)
Fluid retention
Higher estrogen levels
Psychological and emotional stress
Medication noncompliance from fear of side effects
Problems with sleeping
Changes in absorption of anticonvulsants

Anti-epileptic drug levels are monitored at least three times during the pregnancy, more often if seizures are occurring or levels are not normal. Dosage levels should be adjusted accordingly.

Effects of Epilepsy on the Pregnant Patient and the Fetus. Women who become pregnant have a risk for uncontrolled seizures and birth defects from antiseizure medications. In studies of women who were carefully monitored, however, 95% of pregnancies (which is close to normal) had favorable outcomes.

Isolated seizures do not appear to pose any adverse effects to the mother or the unborn child, but repeated seizures and status epilepticus can lead to great dangers. In one study, the effect of epilepsy on complications during pregnancy was the same as in non-epileptic women except for a higher rate of premature deliveries (8.2% in the women with epilepsy).

Drugs Used During Pregnancy. Some types of anti-epileptic drugs (AEDs) can increase the risks for birth defects, especially when taken during the first trimester of pregnancy. Expert guidelines advise that pregnant women use the most effective medication for their type of epilepsy at the lowest dose possible to control seizures. They should also have their doctors take blood tests during pregnancy to monitor their drug levels.

The fetus should be carefully monitored with ultrasonic evaluation and sometimes amniocentesis (visual tests and examination of the fluid in the womb for birth defects and other fetal problems).

In general, research indicates that 90% of women who take AEDs will give birth to healthy children. Still, doctors recommend that women of child-bearing age use a drug other than valproate if possible.

The risk for malformation is higher when more medications are used. For example, there is a 3% risk of birth defects with women who use one anticonvulsant. The risk increases to 20% when four drugs are used.

Birth Defects Associated with Medication. The most common birth defects related to anti-epileptic drugs are:

Cleft lip or palate (risks from lamotrigine, phenobarbital, phenytoin, valproate especially when taken during the first trimester).
Genital or urinary abnormalities (risk from most standard drugs).
Neural tube defects (NTD) in the skull or spinal column (risk of 2% with valproate and 1% with carbamazepine). These complications are most often due to lower folic acid levels caused by both pregnancy itself and antiseizure drugs. Folic acid supplements can help prevent this problem.
Mental impairment (known risk with phenytoin and valproate; inconclusive in carbamazepine and phenobarbital).
Heart defects (risk from phenobarbital, phenytoin, valproate).

Many antiseizure drugs also cause a deficiency in vitamin K clotting factors that increases the risk for hemorrhage in the newborn. Treatment with vitamin K during the last month of pregnancy and a single dose given to the newborn is recommended.

Labor and Delivery. Seizures occur during labor and after delivery in a small percentage of women with epilepsy. The following labor complications are more common among pregnant women with epilepsy: Vaginal bleeding, anemia, and preeclampsia (extremely high blood pressure in the third trimester). If seizures occur during labor, they are generally treated intravenously with benzodiazepines or phenytoin. If tonic-clonic seizures, absence seizures, or status epilepticus occur, a cesarean section may be appropriate.

Postnatal Care

Monitoring the Infant. The infant should be thoroughly examined for any birth defects. Also, if the mother was given phenobarbital or primidone while pregnant, the infant should be monitored for up to 8 months to see if withdrawal symptoms develop. Drug dosages will also need to be adjusted for the mother after delivery.

Breast-feeding. Women on most AEDs typically can nurse their babies, since usually only a small amount of the drug enters the breast milk. The lowest levels are with phenytoin and valproate. (Ethosuximide and possibly levetiracetam are exceptions and should be avoided when a woman is breast-feeding. Women taking phenobarbital are also usually advised not to nurse.) A mother should watch for signs of lethargy or extreme sleepiness in her infant, which could be caused by her medication.

Diagnosis

An epilepsy diagnosis is often made during an emergency visit for a seizure. If a person seeks medical help for a previous or suspected seizure, the doctor will ask about the patient's medical history, including seizure events.

Conditions that cause similar symptoms to epilepsy include:

Syncope. Syncope, a brief lapse of consciousness in which blood flow is reduced to the brain, can mimic epilepsy. It often misdiagnosed as epilepsy. Patients with syncope do not have the rhythmic contracting and then relaxing of the body's muscles.
Migraines. Migraine headaches, particularly migraine with auras, may sometimes be confused with epilepsy. With epileptic seizure, the preceding aura is often seen as multiple, brightly colored, circular spots, while migraine sufferers tend to see black, white, or colorless lined or zigzag flickering patterns. Typically the migraine pain expands gradually over minutes toward one side.
Panic Attacks. In some patients, partial seizures may resemble a panic disorder. Symptoms of panic disorder include palpitations, sweating, trembling, sensation of breathlessness, chest pain, feeling of choking, nausea, faintness, chills or flushes, fear of losing control, and fear of dying.
Narcolepsy. Narcolepsy, a sleep disorder that causes a sudden loss of muscle tone and excessive daytime sleepiness, can be confused with epilepsy.

Electroencephalogram (EEG). The most important diagnostic tool for epilepsy is an EEG, which measures brain waves. Ideally, it should be performed within 24 hours of a seizure. An EEG recording session may last for less than an hour, but in some cases the doctor will want a day-long recording. Long-term monitoring may be necessary in some cases when patients do not respond to medications. Portable EEG units are available in some places, which can be used to monitor patients throughout normal activities. EEGs are not foolproof. Repeated EEGs are often needed to confirm a diagnosis, particularly for certain partial seizures that often produce an initially normal EEG reading.

Video Electroencephalography (Video EEG). For this task, patients are admitted to a special part of the hospital where they are monitored both by EEG and are also watched by a video camera. Patients may need this for a variety of reasons including withdrawal or addition of medications in a patient with difficult-to treat-epilepsy, before epilepsy surgery for some patients, and also when psychogenic nonepileptic seizures are suspected.

Computerized Tomography (CT) Scans. Usually, the first brain imaging test ordered for most adults and children with first-time seizures is a CT scan. This imaging technique is sensitive enough for most purposes. In children, even if the scan is normal, the doctor will follow up to be sure other problems are not present.

A CT (computed tomography) scan is a much more sensitive imaging technique than x-ray, allowing high definition of both the bony structures and the soft tissues. Clear images of organs such as the brain, muscles, joint structures, veins and arteries, as well as anomalies like tumors and hemorrhages may be obtained with or without the injection of contrasting dye.

Magnetic Resonance Imaging (MRI). Experts strongly recommend MRIs for children with first seizures in certain cases, such as children under 1 year old and those with seizures that are associated with any unexplained significant mental or motor problems. These images may help to determine if the disorder can be treated with surgery, and may be used as a guide for surgeons.

Other Advanced Imaging Techniques. More advanced scanning techniques are emerging as important tools for epilepsy researchers. By detecting abnormalities, such as changes in brain activity, positron emission tomography (PET) may help locate damaged or scarred locations in the brain where partial seizures are triggered. These findings may help determine which patients with severe epilepsy are good candidates for surgery. Single-photon emission computer tomography (SPECT) may also be used to decide if the surgery should be performed and what part of the brain needs to be removed. Both of these imaging techniques are generally only needed when an MRI of the brain has not been helpful.

Treatment

You cannot stop a seizure, but you can help the patient prevent serious injury.

Remain calm, and do not panic, then take the following actions:

Wipe away any excess saliva to prevent obstruction of the airway. Do not put anything in the patient's mouth. It is an old wives' tale that people having seizures will swallow their tongues.
Turn the victim gently on the side. Do not try to hold the patient down to prevent shaking.
Rest the patient's head on something flat and soft to protect it from banging on the floor and to support the neck.
Move sharp objects out of the way to prevent injury.

Do not leave the seizure victim alone. Anyone nearby should call 911. Patients should be taken to an emergency room when:

A first-time seizure occurs
Any seizure lasts beyond 2 - 3 minutes
The patient has been injured
The patient is pregnant
The patient is diabetic
Parents, caregivers, or bystanders are at all uncertain

Not all patients with chronic epilepsy need to go to the hospital after a seizure. Hospitalization may not be necessary in many patients whose seizure is not severe or repetitive, and who have no risk factors for complications. All patients or caregivers, however, should contact their doctor after a seizure occurs.

Initial Management. The earlier a patient is treated, the better the results. Initial management of status epilepticus consists of:

Administer any seizure medications
Support systems to maintain or attain normal breathing, blood pressure, electrolyte balances, body temperature, and heart functions
Oxygen for patients who may need it
Attention by medical personnel trained to determine any treatable cause of status epilepticus, such as drug withdrawal, low blood sugar, infection, substance abuse (particularly cocaine), or eclampsia (elevated blood pressure induced by pregnancy)

Medications for Status Epilepticus. Doctors will try one or more of the following medications initially:

Benzodiazepine. An intravenously (IV), intramuscularly, or rectally administered benzodiazepine such as lorazepam (Ativan), diazepam (Valium), clonazepam, or midazolam (Versed) is usually used.
Phenytoin or Fosphenytoin. Many doctors use phenytoin or fosphenytoin if seizures are not controlled by a benzodiazepine.
Phenobarbital. Although effective, barbiturates, such as phenobarbital (Barbita, Luminal), are generally used only when other drugs have failed.

All of these medications carry a risk for hypotension, an abrupt and possibly dangerous drop in blood pressure, which may require treatment.

Treatment After The First Seizure

Children with febrile seizures rarely have any long-term effects and generally do not require drug treatment. In very rare cases, children experience severe fever-related seizures known as complex febrile convulsions. In such cases, there is a risk for brain injury that may lead to temporal lobe epilepsy, but this is very small. Such seizures last over 15 minutes, occur more than once within 24 hours, and may affect only one side of the body.

Treatment with anti-epileptic drugs (AEDs) is usually initiated or strongly considered for the following patients:

Children and adults who have had two or three seizures, unless there is either a long separation between seizures or the seizure is provoked by an injury or other specific causes. (In children, risk for recurrence after a single unprovoked seizure is rare. The risk even after a second seizure is low, even when the seizure is prolonged.)
Children and adults after a single seizure if tests reveal any brain injury, or if specific syndromes put a person at special risk for recurrence, for instance, in cases of myoclonic epilepsy.

There is some debate about whether to treat every adult patient with an AED after a single initial seizure. Some experts do not recommend treating adult patients after a single seizure if they have a normal neurologic examination, EEG, and imaging studies. A 2005 study of patients with single or infrequent seizures found that while early AED treatment reduced the risk of seizure for a few years, it had no effect on long-term outcomes. This study also suggested that delaying AED treatment does not increase the risk of developing lifelong epilepsy.

Some doctors believe, however, that any adult who has a first seizure should begin on-going AED treatment, since 30 - 70% of these patients are likely to experience a subsequent event. According to one study, when young adults were given a single drug (usually carbamazepine) after a first generalized seizure, only 22% had a subsequent seizure compared to about 70% of those who were not given treatment.

Most epileptic seizures can be controlled using a single-drug regimen. First-line AED drugs include phenytoin (Dilantin), carbamazepine (Tegretol, Carbatrol), and divalproex sodium (Depakote). Patients generally begin with low doses and build up until the seizures are controlled or a toxic reaction occurs. If a single drug fails to control seizures, other drugs are added on. The specific drugs and whether more than one should be used are determined by various factors, including the patient's age and the seizure's type, frequency, and cause.

Drugs fail to control epilepsy in about 30% of patients. For patients who have little or no benefit from their initial drug regimen the likelihood of good or complete control from different medications or multidrug regimens is not very high.

Reasons for Failure. An AED may fail to reduce seizures due to such factors as:

The wrong dose level.
Improper timing.
Introducing the medication too rapidly.
Not managing conditions that triggered the seizure.
Instability of the drugs. Many of the tablet forms disintegrate easily with moisture, so pills should be stored in a dry place, not in the bathroom, and kept away from heat.
Patients not taking medication as prescribed. Over 40% of patients experience toxic or bothersome effects from older AEDs, which often causes them to withdraw. Among the most distressing are sleepiness, problems in coordination, and weight gain.
Some evidence suggests that about a quarter of patients who do not respond to AEDs actually have nonepileptic seizures that in many cases are caused by psychiatric conditions (such as panic attack or personality disorders).

The doctor should first address these issues. If the patient still does not respond, the doctor will usually try a different drug. If this fails, one or even two additional drugs at a time may be used. When seizures do not respond to the first two or three drugs, the odds of a fourth or fifth working diminish greatly, despite a number of new medications on the market. In such cases, the patient should ask about surgical alternatives.

Healthy Behaviors. In young people, a positive attitude, continued support from family and health care providers, emotional well-being, and good treatment results can increase patient compliance. Unhealthful behaviors, such as smoking and alcohol use, can have a negative effect.

During the first few months of therapy, the doctor will probably order blood tests once or twice to monitor drug levels and, if necessary, adjust dosages. Monitoring is used to check for AED complications, and to be sure the patient is complying with the regimen. Many experts feel, however, that these blood tests are a less reliable indicator of problems than the patient's own self-observations of his or her responses to the drug. For instance, blood tests may suggest that the dosage levels are insufficient according to general standards, yet the individual patient may be seizure-free and leading a normal life. It is very important that women have AED levels monitored during pregnancy.

An estimated 60% of all patients treated effectively can stop taking AEDs within 5 - 10 years. Evidence suggests that medications in children should not be halted for at least 2 years after the last seizure, particularly if they have partial seizures and abnormal EEGs. It is not clear whether children who have been free of generalized seizures need to wait more than 2 years or if they can withdraw earlier.

Children who tend to relapse after withdrawal from treatment usually have the following conditions or situations:

A family history of epilepsy
Require multiple medications to control seizures
Abnormal EEG readings after treatment has started
Partial seizures

There is also no clear evidence on whether adults who are free of any seizure type can safely withdraw from their medications within 2 years of their last seizure of if they should wait.

In any case, attempts to halt drugs should be done during periods when seizures will cause the least harm. For instance, the best time to test the effects of drug withdrawal in teenagers might be about a year before they are eligible to drive.

Anti-epileptic drugs interact with many other drugs, and may cause special problems in older patients who use multiple medications for other health problems. Elderly patients should have liver and kidney function tests performed before starting antiseizure medication. Standard drugs are usually effective, while safe, newer ones (including gabapentin, lamotrigine, oxcarbazepine, and gamma-vinyl-GABA) may sometimes prove to be useful as a sole therapy. These newer drugs also increase patient compliance because they tend to have fewer side effects than the older ones.

Hormonal fluctuations affect epilepsy in about a third to a half of female patients. Estrogen appears to increase activity, and progesterone reduces it. The effect of pregnancy on women with epilepsy is complex. The following treatments may help or affect women with epilepsy:

Hormonal Drugs that Suppress Ovulation. When seizures in women are worsened by hormonal changes, such as during the menstrual cycle, suppressing ovulation may be recommended using drugs called gonadotropin-releasing hormone agonists.
Oral contraceptives. Antiseizure medications affect many oral contraceptives (OCs). Carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, and topiramate reduce the effects of OCs. Valproate does not, and may even increase hormonal levels. Gabapentin, lamotrigine, tiagabine, and vigabatrin may also prove to be safe with OCs, but more research is needed. Progestins may be the best contraceptive drugs for women with epilepsy at this time. Injected progestins may actually help prevent seizures in some cases.

More information on epilepsy and pregnancy can be found in this report under Outlook and Effects.

Medications

Many newer anti-epilepsy drugs (AEDs) are now available and are usually better tolerated than the older, standard AEDs. They often cause less sedation and require less monitoring. Although they are generally approved for use as add-ons to standard drugs that fail to control seizures, many doctors are now prescribing them as single drugs. Specific choices usually depend on the individual's particular condition and the specific side effects of the AED. None has emerged as being superior to either standard or newer drugs. All appear to offer some benefits, but, as with standard antiseizure drugs, they also have troublesome side effects.

Valproate (Depakene, valproic acid) and its delayed release form, divalproex sodium (Depakote), are anticonvulsants. Valproate is the most widely prescribed anti-epileptic drug worldwide.

Uses. Valproate is the first choice for patients with generalized seizures and is used to prevent nearly all other major seizures as well.

General Side Effects. These drugs have a number of side effects that vary depending on dosage and duration. Most side effects occur early in therapy and then subside. General side effects include:

Stomach and intestinal problems, which are experienced by nearly half of patients after starting the drugs and may still occur after several years of use. Divalproex sodium (Depakote) has a lower risk for these side effects than valproate (Depakene).
Increased appetite with significant weight gain often becomes a problem and can be a major reason for noncompliance, particularly in young people.
Hand tremors, irritability, and hyperactivity in children are fairly common.
Temporary hair thinning and hair loss have occurred. Taking zinc and selenium supplements may help reduce the effect.
Young girls may develop secondary male characteristics, and premenopausal women are at increased risk for menstrual irregularities and polycystic ovaries, due to elevated male hormones. The effects are reversible. (These side effects also appear in women using other anti-epileptic drugs, but the risk from valproate appears to be higher.)
Studies have reported symptoms of Parkinson's disease preceded by hearing loss in people who have taken it for more than a year, but they were reversible when the drug was withdrawn.
Valproate poses a higher risk for serious birth defects than many other AEDs. These birth defects include skull and limb deformities, and brain, heart, and lung problems. Experts recommend that women of child-bearing age use a different type of anti-epilepsy drug than valproate. If valproate is used, it should be prescribed at the lowest possible dose.
Cases of pancreatitis, a serious and even life-threatening inflammation in the pancreas, have been reported in children and adults taking valproate. (It is still very rare, however.)
Valproate and divalproex sodium are not usually recommended for young children because of an unusual, but potentially fatal, toxic effect on the liver. This very rare effect is most likely to affect children under 2 years of age who have birth defects and are taking more than one antiseizure drug. Some doctors recommend monitoring blood levels for liver function once prior to administering valproate or divalproex sodium, monthly during the first 6 months, and then periodically after that.
Children with epilepsy who take valproic acid may eventually develop some problems in the kidney, although they are generally not significant.

Symptoms of Toxic Side Effects in Liver or Pancreas.

Abdominal pain
Nausea or vomiting
Loss of appetite
Lethargy
Acute confusion
Water retention
Easy bruising
Yellowish skin coloring

Carbamazepine (Tegretol, Equetro, Carbatrol) is an effective anticonvulsant and specific analgesic when used alone or with other drugs. Carbamazepine also has the added benefit of relieving depression and improving alertness. An extended release form is available that allows twice-daily dosing rather than 3 times a day. A chewable form makes it easier for children to take.

Uses. This drug is used to prevent the following seizures or epilepsy syndromes:

Partial seizures. Patients tend to tolerate this drug better than others, although responses differ among individuals
Grand mal seizures
Combinations of grand mal and partial seizures
Autosomal dominant nocturnal frontal lobe epilepsy (an inherited disorder).

Side Effects. Different side effects may develop or resolve at different points in the treatment duration. Initial side effects may include:

Double vision, headache, sleepiness, dizziness, and stomach upset. These usually subside after a week and can be greatly reduced by starting with a small dose and building up gradually.
Some people experience visual disturbances, ringing in the ears, agitation, or odd movements when drug levels are at their peak. The extended-release form of carbamazepine (Carbatrol) may help reduce these symptoms.

Serious side effects are less common but can include:

Carbamazepine may increase the risk for birth defects, especially if it is taken during the first trimester of pregnancy.
Skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome, so severe the drug has to be discontinued develop in about 6% of patients. These skin reactions cause skin lesions, blisters, fever, itching, and other symptoms. People of Asian ancestry have a 10 times greater risk for skin reactions than other ethnicities. The FDA recommends that patients of Asian ancestry get a blood test prior to starting the drug to determine if they have the gene variant that increases this risk.
Water retention can be a problem in older people.
Hormonal changes, particularly higher levels of male hormones in both men and women, pose some risk for sexual dysfunction over time.
A decrease in white blood cells occurs in about 10% of those taking the drug. This is generally not serious unless infection accompanies it.
Other blood conditions can arise that are also potentially serious. Patients should be sure to inform the doctor if they have any sign of irregular heartbeats, sore throat, fever, easy bruising, or unusual bleeding.
Long-term therapy can cause bone loss (osteoporosis) in women, who should take preventive calcium and vitamin D supplements.
Children are at higher risk for behavioral problems.

Note: Citrus fruit, especially grapefruit, can increase carbamazepine's adverse effects and should be avoided by those taking this drug.

Uses. Phenytoin (Dilantin) is effective for adults who have the following seizures or conditions:

Grand mal seizures
Partial seizures
Status epilepticus
Can be effective for people with head injuries who are at high risk for seizures

This drug is not useful for the following seizures:

Petit mal seizures
Myoclonic seizures
Atonic seizures

Side Effects. Side effects are sometimes difficult to control. Some people may develop a toxic response to normal doses, while others, such as those with alcoholism, may require higher doses to achieve benefits. As with any drug, side effects generally rely on dosage and duration. Using phenytoin in combination with newer add-on drugs can allow lower doses and may reduce some of the risks. Side effects may include:

Excess body hair, eruptions and coarsening of the skin, and weight loss
Gum disease
Staggering, lethargy, nausea, depression, eye-muscle problems, anemia, and an increase in seizures can occur as a result of high doses.
Liver damage may develop in rare cases.
Bone loss from long-term therapy. Patients should take preventive calcium and vitamin D supplements and exercise regularly to improve bone mass.
Severe and even rare life-threatening skin reactions (Stevens-Johnson syndrome)
An increased risk for birth defects

Phenobarbital (Luminal), also called phenobaritone, is a barbiturate anticonvulsant and is often the initial drug prescribed for newborns and young children. It is a relatively inexpensive drug. Primidone (Mysoline) is converted in the body to phenobarbital, and has the same benefits and adverse effects. It is reported that primidone is not as well-tolerated as phenobarbital. Some experts believe that primidone has no advantage over the other drug.

Uses. Barbiturates are used to also prevent grand mal (tonic-clonic) seizures or partial seizures. They are no longer typically used as a first-line drug.

Side Effects. Phenobarbital has fewer toxic effects on other parts of the body than most anti-epileptic drugs, and drug dependence is unusual, given the low doses used for patients with epilepsy. Nevertheless, withdrawal is common because of side effects, and therefore it is less likely to be used over time than other drugs, including phenytoin, another relatively inexpensive but effective drug.

Patients sometimes describe their state as "zombie-like." The most common and troublesome side effects are:

Drowsiness
Memory problems
Problems with tasks requiring sustained performance
Problems with motor skills
Hyperactivity in some patients, particularly in children and the elderly
Depression in some adults

Some controversy has arisen over studies indicating that children taking phenobarbital score lower on intelligence tests, even for some months after going off the drug.

Uses. Ethosuximide (Zarontin) is used for petit mal (absence) in children and adults when the patient has experienced no other type of seizures. Ethosuximide succeeds in abolishing petit mal seizures in 60% of patients and controls them in up to 90%. Methsuximide (Celontin), a drug similar to ethosuximide, may be suitable as an add-on treatment for intractable epilepsy in children without causing serious or permanent side effects.

Side Effects. Use of this drug can cause stomach problems, dizziness, loss of coordination, and lethargy. In rare cases, it has caused severe and even fatal blood abnormalities. Periodic blood counts are recommended for patients taking this drug.

Uses. Clonazepam (Klonopin) is recommended for myoclonic and atonic seizures that cannot be controlled by other drugs and for Lennox-Gastaut (absence variant). It may be useful in newborns when other drugs are ineffective. Although clonazepam can prevent generalized or partial seizures, patients generally develop tolerance to the drug, and then seizures recur.

Side Effects. People who have had liver disease or acute angle glaucoma should not take clonazepam, and people with lung problems should approach the drug with caution. Clonazepam can be addictive, and abrupt withdrawal has been known to trigger status epilepticus. Side effects include the following: drowsiness, imbalance and staggering, irritability, aggression, hyperactivity in children, weight gain, eye muscle problems, slurred speech, tremors, skin problems, and stomach problems.

Uses. Lamotrigine (Lamictal) is approved as add-on (adjunctive) therapy for partial seizures, and generalized seizures associated with Lennox-Gastaut syndrome, in children aged 2 years and older and in adults. Lamotrigine is also approved as add-on therapy for treatment of primary generalized tonic-clonic (PGTC) seizures, also known as “grand mal” seizures, in children aged 2 years and older and adults. Lamotrigine can be used as a single drug treatment (monotherapy) for adults with partial seizures who have not responded to monotherapy with carbamazepine, phenytoin, phenobarbital, primidone, or valproate. Birth control pills lower blood levels of lamotrigine.

Side Effects. Common side effects include dizziness, headache, blurred or double vision, lack of coordination, sleepiness, nausea, vomiting, insomnia, and rash. Although most cases of rash are mild, in rare cases the rash can become very severe. The risk of rash increases if the drug is started at too high a dose or if the patient is also taking valproate. (Serious rash is more common in young children who take the drug than it is in adults.) Rash is most likely to develop within the first 8 weeks of treatment. Be sure to immediately notify your doctor if you develop a rash, even if it is mild.

Studies suggest that lamotrigine may cause fewer problems with sexual function in men than other antiseizure drugs. A 2006 study indicated that lamotrigine may cause fewer cognitive problems (such as confusion and difficulty concentrating) than topiramate.

Gabapentin (Neurontin) is an effective add-on drug for controlling complex partial seizures and secondarily generalized partial seizures and is approved for adults and children with these seizures. It has achieved response rates in patients with resistant partial epilepsy. It is not at all useful for generalized petit mal seizures.

Side Effects. Its toxicity is low, and side effects include sleepiness, headache, fatigue, and dizziness. Some weight gain has been reported. Gabapentin has no significant interactive effects when taken with other drugs. Children may experience hyperactivity or aggressive behavior. Long-term adverse effects are still unknown.

Pregabalin (Lyrica) is similar to gabapentin.

Uses. Approved as add-on therapy to treat partial-onset seizures in adults with epilepsy. In clinical trials, half of the patients who received pregabalin experienced a 50% reduction in seizure frequency.

Side Effects. These may include dizziness, sleepiness, dry mouth, swelling in hands and feet, blurred vision, weight gain, and trouble concentrating

Uses. Topiramate (Topamax, generic) is similar to phenytoin and carbamazepine and is effective and safe for a wide variety of seizures in adults and children. It is approved as add-on therapy for patients 2 years and older with generalized tonic-clonic seizures, partial-onset seizures, or seizures associated with Lennox-Gastaut syndrome. It is also approved as single therapy for patients 10 years and older with tonic-clonic seizures or partial-onset seizures. Studies have shown a 34 - 87% reduction in seizure frequency with some patients becoming seizure-free.

Side Effects. Most side effects are mild to moderate and can be reduced or even prevented by beginning at low doses and increasing dosage gradually. Serious side effects may include glaucoma, decreased sweating, increased body temperature, kidney stones, sleepiness, dizziness, confusion, and trouble concentrating. Patients should immediately tell their doctor if they have blurred vision or eye pain. Topiramate may have fewer interactions with oral contraceptives than other AEDs.

Oxcarbazepine (Trileptal, generic) is similar to phenytoin and carbamazepine but generally has fewer side effects.

Uses. Approved as single therapy or add-on therapy for partial seizures in adults and for children ages 4 years and older.

Side Effects. Serious side effects, while rare, include Stevens-Johnson syndrome and toxic epidermal necrolysis. These skin reactions cause a severe rash that can be life threatening. Rash and fever may also be a sign of multi-organ hypersensitivity, another serious side effect associated with this drug. Oxcarbazepine can also reduce sodium levels (hyponatremia). Your doctor may want to monitor the sodium level in your blood. This drug can also reduce the effectiveness of birth control pills. Women who take oxcarbazepine may need to use a different type of contraceptive.

Zonisamide (Zonegran) is a unique drug that blocks sodium and calcium channels and may have nerve-protecting properties.

Uses. It is approved as add-on therapy for adults with partial seizures, and studies indicate it is often effective against infantile spasms (West syndrome) and myoclonic seizures.

Side Effects. Zonisamide increases the risk for kidney stones, which can be reduced with increased fluid intake and citrate. It has also been associated with reduced sweating and a sudden rise in body temperature, especially in hot weather. Children are especially at risk for this side effect, which can be serious. (The drug has not been approved for children.) Other side effects tend to decrease over time and include dizziness, forgetfulness, headache, weight loss, and nausea.

Levetiracetam (Keppra) is known as a nootropic drug.

Uses. This drug is approved both in oral and intravenous forms as add-on therapy for:

Partial onset seizures in adults and children ages 4 years and older
Myoclonic seizures in adults and adolescents ages 12 years and older who have juvenile myoclonic epilepsy
Primary generalized tonic-clonic seizures in adults and children ages 6 years and older who have idiopathic generalized epilepsy

Some experts believe that levetiracetam represents a significant advance and will prove to be an important first-line drug. Levetiracetam appears to have fewer drug interactions than other anti-epileptic drugs and may be particularly useful for older patients.

Side Effects. These tend to occur mostly in the first month. They include sleepiness and fatigue, muscle weakness and coordination difficulties, headache, flu symptoms, dizziness, behavioral abnormalities, possible risk of a reduced white blood cell count, and a higher rate of infections. Caution is advised for patients with kidney dysfunction. There have been some reports of adverse effects on mood (irritability, depression, and anxiety), but recent studies have found fewer such effects than with other AEDs. Epilepsy, rather than the drug, is likely to be the cause of these mood changes. About 1% of patients report considerable weight loss.

Tiagabine (Gabitril) has properties similar to phenytoin and carbamazepine, and is also showing promise.

Side Effects. Evidence has reported some significant side effects with its use, including dizziness, fatigue, agitation, and tremor. At least one study suggested that it has more adverse effects than lamotrigine and is not as well tolerated. In February 2005, the FDA issued a warning advising that tiagabine may cause seizures in patients without epilepsy. Tiagabine is only approved for use with other anti-epilepsy medicines to treat partial seizures in adults and children 12 years and older.

Felbamate. Felbamate (Felbatol) is an effective antiseizure drug. However, after reports of deaths from a serious blood condition known as aplastic anemia or from liver failure, felbamate is recommended only under certain circumstances. They include severe epilepsy, such as Lennox-Gastaut syndrome or as monotherapy for partial seizures in adults when other drugs fail.

Vigabatrin. Vigabatrin (Sabril) is a chemical called gamma-vinyl GABA. It was designed to increase the brain levels of gamma aminobutyric acid (GABA), the enzyme that inhibits seizure activity. It has serious side effects, however, and is generally prescribed in the U.S. only in certain cases, such as in low doses for patients with Lennox-Gastaut syndrome. Overseas it is also used for partial seizures and as first-line therapy in children with infantile spasms (West syndrome). Between 10 - 30% of people on long-term treatment have developed irreversible visual disturbances, including reductions in acuity and color vision. Men are at higher risk for this side effect than are women. Further studies are needed to determine the extent and severity of this complication, particularly in children. There is a slight risk for depression or psychosis when vigabatrin is used as add-on therapy, and particularly if the drug is administered too quickly. These risks are far lower if the drug is used as sole therapy.

Older Drugs. Some older but less effective drugs may still play a role against epilepsy:

Acetazolamide (Diamox) is sometimes used against common types of seizures, but patients quickly develop a tolerance for it. Some experts suggest it still may be useful when drug interactions are a problem, when a rapid effect is required, or when an additional drug is needed for a short time.
Trimethadione (Tridione) is effective for petit mal seizures, but has very serious side effects, and its use is severely limited.

Infantile spasms are treated with vigabatrin, adrenocorticotropic hormone (ACTH), or valproate. Some experts recommend that vigabatrin be given first and ACTH administered 10 - 14 days later. In one small study, no infants who were given this combination relapsed after 4 months. Newer drugs may also be effective for this problem, but their effects on small children are not yet wholly known.

New AEDs. Retigabine is an investigational GABA enhancer that works in a different way from existing AEDs. It is currently in phase III trials for treatment of partial-onset seizures in patients who are receiving other AEDs. Talampanel is another new type of drug, known as an AMAP receptor antagonist, that is currently in early trials. Other drugs under investigation are related to existing AEDs. For example, brivaracetam and seletracetam are similar to levetiraceptam, fluorofelbamate is similar to felbamate, and eslicarbazepine is similar to oxcarbazepine.

Cannabinoids. Cannabinoids are compounds in marijuana (cannabis) that may have properties that protect nerve cells. Some patients claim a reduction in seizures while other active users of marijuana report no effect on seizures. No one has reported worse seizures from the drug. Animal studies further support some protection from cannabinoids against seizures. Clinical studies using humans have not been conducted.

Melatonin. Melatonin is a hormone found in the brain that is best known for its role in sleep. Some researchers believe that it might have properties that could benefit patients with epilepsy. Melatonin is a powerful hormone that can have major effects on all parts of the body. No one with epilepsy should experiment with this supplement except as part of a clinical trial. In some studies, melatonin has been found to cause seizures in children who have existing neurologic problems.

Surgery

Surgical techniques to remove injured brain tissue may be appropriate for many patients with epilepsy. The surgeon's goal is to remove only the damaged tissue in order to prevent seizures and to avoid healthy brain tissue. Surgical techniques for reaching these goals have improved significantly over the past decades due to advances in imaging and monitoring, new surgical techniques, and a better understanding of the brain and epilepsy.

A number of tests using imaging and electroencephalography (EEG) can determine if surgery is an option:

The general approach is to first use long-term EEG monitoring to locate the brain tissue that triggers the epileptic event.
Advanced imaging techniques can provide valuable additional information. They include functional magnetic resonance imaging (fMRI), positron emission tomography (PET), or single-photon emission computer tomography (SPECT) scans.

If the imaging tests indicate that more than one site is involved or their results conflict, then more invasive monitoring of the brain may be required, although the newer imaging tests are proving to be very accurate tools. If such tests pinpoint a specific area in the brain as the location for seizures, surgery is possible. MEG, for example, is now approved for imaging parts of the brain involved with motor control, sensation, and language function, and may become important in evaluating patients who are likely candidates for surgery. The doctor will also examine the test results to determine if the offending nerve cells perform vital functions and try to predict surgical outcome in certain cases.

The major areas of the brain have one or more specific functions.

The most common surgical procedure for epilepsy is temporal lobectomy, which is performed when epilepsy occurs in the temporal lobe. (Surgery is not as successful in epilepsies that occur in the frontal lobe.) It involves removing small portions from the hippocampus. The hippocampus is a part of the brain that is involved in memory processing. It is part of the limbic system, which controls emotions.

Click the icon to see an image of the limbic system of the brain.

Candidates. Candidates for this surgery usually have a history of seizures. Anti-epileptic drugs have not helped them. Young children may be more difficult candidates because they often have injured areas outside the temporal lobes. Nevertheless, surgery can be very successful in many children, even if more than one area is involved.

Success Rates. New imaging techniques are dramatically improving the success rates of temporal lobe surgery. Studies have shown that many patients remain seizure-free after temporal lobectomy. In a randomized controlled trial, around 60% of patients became free of disabling seizures after surgery versus only 8% of patients treated with medications. In general, around 60 - 80% of patients are seizure free 1 - 2 years after surgery.

Patients may still need to take medications after surgery, even if seizures are very infrequent. Cure is not always possible, and some patients may still experience some seizures. Double vision is very common after the operation, but it is typically temporary and resolves within a few months.

Studies also suggest that temporal lobe surgery improves quality of life and can help relieve depression and anxiety. Other studies indicate that surgery may even prolong survival. Some experts theorize that surgery stabilizes parts of the brain that influence heart rate and may reduce the risk of sudden death, a rare complication of epilepsy.

Effects on Mental Functioning. Although surgery on the left temporal lobe does not impair intelligence to any significant degree, some studies suggest negative effects of mental functioning and behavior. A risk of impairment of verbal memory is also present.

In general, surgical effects on mental functioning and behavior depend on the extent and location of the surgical area.

Lesionectomy is a procedure that removes abnormal tissues in certain conditions, such as:

Cavernous angiomas (abnormal clusters of blood vessels)
Low-grade brain tumors
Cortical dysplasias (these are abnormalities in fetal development in which the normal migration of nerve cells is altered for some reason)

This local surgery, which can cure the patient's epilepsy, has become possible with the advent of advanced imaging techniques such as MRI.

Other surgical procedures called hemispherectomy and corpus callosotomy offer hope for specific patients. They include infants and young children with catastrophic seizures that occur in one, or part of, a hemisphere and for patients whose seizures are due to specific structural brain abnormalities or tumors.

Hemispherectomy. Hemispherectomy is the removal of half the brain, leaving the deep structures intact. Surgery can take 12 hours and there is always some paralysis on one side of the body. There is also a small risk for hydrocephalus, coma, or even death. Quality of life is almost always improved, however, and the surgery does not reduce intelligence.

Corpus Callosotomy. Corpus callosotomy involves cutting the nerve fibers that connect one side of the brain to another. It does not remove brain tissue. It may be done in two stages. In the first, there is a partial separation. If seizures continue, the surgeon may perform a complete separation. This surgery can reduce (although not entirely stop) uncontrolled tonic clonic seizures. It has been used in patients with specific syndromes, such as Lennox-Gastaut syndrome. The procedure can have very severe complications, however.

Electrical stimulation of areas in the brain that affect epilepsy is helping many patients with refractory epilepsy. Vagus nerve stimulation (VNS), an electrical stimulation of the vagus nerve, is now an accepted therapy for severe epilepsy that does not respond to AEDs. The two vagus nerves are the longest nerves in the body. They run along each side of the neck, then down the esophagus to the gastrointestinal tract. They affect swallowing, speech, and many other functions. They also appear to connect to parts of the brain that are involved with seizures. The procedure is as follows:

Click the icon to see a depiction of epilepsy treatment.

A battery-powered device similar to a pacemaker is implanted under the skin in the upper left of the chest.
A lead is then attached to the left vagus nerve in the lower part of the neck.
The neurologist programs the device to deliver mild electrical stimulation to the vagus nerve. (Patients may also pass a magnet over the device to give it an extra dose if they sense a seizure coming on. This appears to help about 25 - 30% of patients.)
The batteries wear out after 3 - 5 years and need to be removed and replaced by a simple surgical procedure.

An investigational approach called deep brain stimulation (DBS) targets the thalamus, the part of the brain that produces most epileptic seizures. Early results have been promising. Researchers are also studying other implanted brain and nerve stimulation devices such as the responsive neurostimulator system (RNS), which detects seizures and stops them by sending electrical stimulation to the brain. A third investigational approach, trigeminal nerve stimulation (TNS), stimulates a nerve involved in inhibiting seizures.

Candidates. The American Academy of Neurology recommends VNS for:

Patients who are over 12 years old, and
Have partial seizures that do not respond to medication, and
Are not appropriate candidates for surgery

Evidence is accumulating, however, to indicate that VNS is effective and safe for many patients of all ages and for refractory epilepsy of many types.

Success Rates. Studies are reporting that the procedure reduces seizures within 4 months by up to 50% and even more in many patients. Studies report that it has been effective for longer than 7 years. In one study that followed patients for a year, the benefits of VNS appeared to increase over time.

Complications. Vagus nerve stimulation does not eliminate seizures in most patients and is still somewhat invasive. VNS can cause shortness of breath, hoarseness, sore throat, coughing, ear and throat pain, or nausea and vomiting. These side effects can be reduced or eliminated by reducing the intensity of stimulation. Some studies suggest that the treatment causes adverse changes in breathing during sleep and may cause lung function deterioration in people with existing lung disease. People who have obstructive sleep apnea also should be cautious about this procedure. Turning off the VNS (for example before an MRI or surgery) may increase the risk for status epilepticus. (However, VNS may also be helpful for treating status epilepticus in some patients.)

Stereotactic Radio Surgery. Focused beams of radiation are able to destroy lesions deep in the brain without the need for open surgery. Typically used for brain tumors, stereotactic radio surgery is also under investigation for temporal lobe epilepsy and for seizures due to cavernous malformations. It may be used for patients when an open surgical approach is not possible.

Lifestyle Changes

The best preventive measure is to comply strictly with the drug regimen as prescribed. Seizures cannot be prevented by lifestyle changes alone, but people can make behavioral changes that improve their lives and give them a sense of control.

In most cases, there is no known cause for epileptic seizures, but specific events or conditions may trigger them and should be avoided.

Inadequate or Fragmented Sleep. Inadequate or fragmented sleep can set off seizures in many people. In one study, the lowest risk for seizures was during REM sleep (when dreams occur). The highest risk was during light non-REM stages of sleep. Using sleep hygiene or other methods to improve sleep may be helpful.

Food Allergies. Food allergies may provoke seizures in children who also have migraine headaches, hyperactive behavior, and abdominal pains. Parents should consult an allergist if they suspect foods or additives might be playing a role in such cases.

Alcohol and Smoking. Alcohol and smoking should be avoided, although light alcohol consumption does not appear to increase seizure activity in people who are not alcoholics or sensitive to alcohol.

Flashing Lights. Patients should avoid exposure to flashing or strobe lights. Video games have been known to trigger seizures in people with existing epilepsy, but apparently only if they are already sensitive to flashing lights. Seizures have been reported in Japan among people who watched cartoons with rapidly fluctuating colors and quick flashes. The frequency of flashes per second is measured in hertz (Hz). Screens that emit a lower hertz (such as 50 Hz screens sold in Europe) are more likely to cause seizures in people with epilepsy than a higher-hertz screen (such as 100 Hz screens sold in the U.S.).

Relaxation methods include diaphragmatic rhythmic breathing, biofeedback, and meditation techniques. No strong evidence supports their value on reducing actual attacks (although some people have reported that they have), but they may be helpful in reducing anxiety in people who have positive experiences with them. There have been some reports that deep breathing (a common relaxation technique) triggers seizures in certain people.

Exercise is important for many aspects of epilepsy, although it can be problematic. Weight-bearing exercise helps maintain bone density, which can be reduced by many of the medications, particularly the older ones. Exercise can also help to prevent weight gain, which is a problem with some drugs. There have been some reports that exercise may trigger seizures in some patients, but this is uncommon. A number of studies have found no significant association between physical activity and a higher incidence of seizures in patients with epilepsy. Nevertheless, if patients are concerned they should discuss this issue with their doctors.

Some small studies have reported significant benefits from the practice of yoga, which employs weight bearing and balancing postures. In one study, a system of meditation called Sahaja yoga changed EEG readings of brain waves and reduced seizures. Other studies report a 50% reduction in seizures and an overall decline in the number of attacks per month. Still, well-controlled studies are needed to confirm these benefits.

All patients should maintain a healthy diet, including plenty of whole grains, fresh vegetables, and fruits. In addition, dairy foods may be important to maintain calcium levels. Fasting has been used to prevent seizures since ancient times. In the 1920s, a high-fat, no-sugar, low protein diet, known as a ketogenic diet, was used to prevent seizures. It lost popularity after the introduction of anti-epileptic drugs but is now proving to be effective with many children. Researchers are investigating whether the Atkins diet (high protein, low carbohydrate) may help people with epilepsy. Both the ketogenic diet and the Atkins diet can interfere with some anti-epileptic medications such as topiramate. Talk to your doctor before beginning any special diet or a weight loss program.

The ketogenic diet, which is very high in fat (90%), very low in carbohydrates, and low in protein, has been studied and debated for decades. It has proven to be helpful for many children with severe epilepsy that does not respond to AEDs. It is not clear why it works. The standard theory is that burning fat instead of carbohydrates causes an increase in ketones. Excess ketones (called ketosis) appears to alter certain amino acids in the brain and to increase levels of the neurotransmitter gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing.

Benefits of the Ketogenic Diet. Studies report that about 10 - 15% of children who use the diet are seizure free after 1 year, while 30% are nearly seizure free. Some parents report that the diet helps improve their children’s alertness, even if seizures continue. Many children who try the ketogenic diet are able to stop or at least reduce their medications.

Candidates of the Ketogenic Diet. The Ketogenic Diet seems to be most helpful for children who have difficult-to-control seizures, in particular:

Generalized and partial seizures (the diet does not appear to be as helpful for children with partial-onset seizures)
Myoclonic-atastic epilepsy
Infantile spasm

Typical Ketogenic Diet. (This diet must be professionally monitored! Parents can endanger their children if they try the program on their own without consulting a doctor or trained health expert.) The child fasts for the first 1 - 2 days, then the diet is gradually introduced. The regimen uses small amounts of carbohydrates and large amounts of fats (up to 90%), with very few proteins and no sugar. Children generally consume 75% of their usual daily calorie requirements.

A typical dinner may include a chicken cutlet or piece of fish, broccoli with cheese, lettuce with mayonnaise, and a whipped cream sundae. Vegetables may include celery, cucumbers, or asparagus, cauliflower, and spinach. Breakfast might consist of an omelet, bacon, and cocoa with cream. (Artificial sweeteners are used for any desserts.)

The diet is difficult, as a slight deviation from the diet can provoke a seizure. Children cannot take medications that contain sugar (which is common in many drugs produced for children). Some sunscreens and lotions contain sorbitol, a carbohydrate that can be absorbed through skin. About 40 - 50% of patients find the diet too difficult or ineffective and stop it after 6 months.

Researchers are also investigating the Atkins diet, a popular weight-loss diet that has similar effects but is less restrictive than the ketogenic diet. Early results indicate that it might be helpful for some young people. Another alternative is a low glycemic index diet, which contains even fewer carbohydrates than the Atkins diet. Still, parents should not put their children on these diets without support from a doctor.

Side Effects and Complications. To prevent serious side effects, children need regular monitoring by a doctor, especially when the diet is first initiated.

Side effects or complications that may occur at the start of the diet include:

Acidosis, a build-up of acid in the blood and body
Low blood sugar (hypoglycemia)
Stomach upset
Dehydration
Lethargy

Side effects that may occur later on include:

Unhealthy cholesterol and lipid levels
Kidney stones, which may be a complication of acidosis, occur in about 5% of children on the diet. Patients should drink plenty of fluids. Oral potassium citrate (Polycitra K) may be protective.
Slowing of growth (tends to occur more in younger children than older children
Decreased bone density

Because most patients remain on the diet for only 2 years, the risks for potential long-term damage appear minimal.

Many patients with epilepsy and parents whose children have epilepsy can benefit from support associations. These services are usually free and available in most cities.

Tips for Helping Children. Some of the following tips may help the child with epilepsy:

Children should be treated as normally as possible by parents and siblings.
Children should be assured that they will not die from epilepsy.
Often children can be given the hope that they will outgrow the disorder.
Most children will not have seizures triggered by sports or by any other ordinary activities that are enjoyable and healthy.
As soon as they are old enough, children should be active participants in maintaining their drug regimens, which should be presented in as positive a light as possible.

Therapies for Children and Adults. Because of the risks for serious emotional consequences, psychological therapy may be beneficial and even necessary for some adults and children. In one study, cognitive behavioral therapy was helpful in lowering seizure rates in young people with juvenile myoclonic epilepsy. This approach offers a structured counseling program that helps people change behaviors that can reduce seizure risk factors such as anxiety and insomnia.

Resources

www.epilepsyfoundation.org -- Epilepsy Foundation
www.aesnet.org -- American Epilepsy Society
www.aan.com -- American Academy of Neurology
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke

References

Christensen J, Vestergaard M, Mortensen PB, Sidenius P, Agerbo E. Epilepsy and risk of suicide: a population-based case-control study. Lancet Neurol. 2007 Aug;6(:693-8.

Foldvary-Schaefer N, Wyllie E. Epilepsy. In: Goetz C, ed. Textbook of Clinical Neurology. 3rd edition. Saunders. 2007.

Freeman JM, Kossoff EH, Hartman AL. The ketogenic diet: one decade later. Pediatrics. 2007 Mar;119(3):535-43.

Johnson MV. Seizures in childhood. In: Behrman RE, ed. Nelson Textbook of Pediatrics. 17th edition. Saunders. 2004.

Krebs PP. Psychogenic nonepileptic seizures. Am J Electroneurodiagnostic Technol. 2007 Mar;47(1):20-8.

Krumholz A, Wiebe S, Gronseth G, et al. Practice Parameter: evaluating an apparent unprovoked first seizure in adults (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2007 Nov 20;69(21):1996-2007.

Kwan P, Brodie MJ. Emerging drugs for epilepsy. Expert Opin Emerg Drugs. 2007 Sep;12(3):407-22.

Leone MA, Solari A, Beghi E; FIRST Group. Treatment of the first tonic-clonic seizure does not affect long-term remission of epilepsy. Neurology. 2006 Dec 26;67(12):2227-9.

Salanova V, Worth R. Neurostimulators in epilepsy. Curr Neurol Neurosci Rep. 2007 Jul;7(4):315-9.

Spencer SS. Seizures and epilepsy. In: Goldman L, ed. Cecil Medicine. 23rd edition. Saunders. 2007.

Tomson T, Hiilesmaa V. Epilepsy in pregnancy. BMJ. 2007 Oct 13;335(7623):769-73.

Review Date:
12/31/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Alzheimer's disease

FitSugar — Wed, 08 Oct 2008 17:35:13 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Prevention
Symptoms
Diagnosis
Medications
Stages
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Alzheimer’s Disease Toll Increasing

More than 5 million Americans now have Alzheimer’s disease, and the number could increase to 16 million by mid-century, according to a 2007 report from the Alzheimer’s Association.

New Drug Indication

In 2006, the FDA expanded the use of donepezil (Aricept) to include treatment of people with severe dementia associated with Alzheimer’s disease. Donepezil was previously approved only for people with mild-to-moderate dementia.

Managing Psychotic and Behavioral Symptoms

Newer antipsychotic drugs are no better than placebo for controlling psychosis, aggression, and agitation in patients with Alzheimer’s disease, indicates an important study in the New England Journal of Medicine. In addition, these drugs can cause severe side effects and have been associated with increased death rate.
Non-drug approaches, such as behavioral techniques and bright light boxes, may be helpful for these patients, suggests an Archives of Internal Medicine study.

Brain Exercises Prevent Mental Decline

Cognitive training exercises that help boost memory, reasoning, and processing speed may help slow mental decline and improve functional abilities in older adults, indicates a Journal of the American Medical Association study.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Do Not Prevent Alzheimer’s

The NSAIDs naproxen (Aleve) and celecoxib (Celebrex) do not protect against Alzheimer’s disease, indicates a data analysis from a large-scale U.S. National Institutes of Health (NIH) clinical trial.

Docosahexaenoic Acid (DHA) for Alzheimer’s Prevention

DHA, an omega-3 fatty acid found in some types of fish, may lower the risk for dementia and Alzheimer’s disease as well as delay its progression. However, researchers are uncertain whether DHA dietary supplements provide the same benefits as food sources (salmon, mackerel, and other types of fatty fish). In 2007, the NIH announced the launch of a national clinical trial to evaluate whether DHA can slow cognitive and functional decline in people with mild-to-moderate Alzheimer’s disease.

Support for Caregivers

Intensive programs that combine counseling, support groups, and problem-solving techniques can dramatically improve caregivers’ quality of life and may help delay patients’ transfers to nursing homes, several recent studies suggest.

Introduction

Alzheimer's disease (AD) is a degenerative disease of the brain from which there is no recovery. The disease slowly attacks nerve cells in all parts of the cortex of the brain and some surrounding structures, thereby impairing a person's abilities to govern emotions, recognize errors and patterns, coordinate movement, and remember. Ultimately, a person with AD loses all memory and mental functioning.

The major areas of the brain have one or more specific functions.

Causes

Researchers are finding specific biologic factors involved with Alzheimer's disease. Various environmental and genetic players appear to contribute to or trigger the process by which these factors destroy nerve cells leading to this disease.

Imaging techniques in patients with Alzheimer's disease have found significant loss of cells and volume in the regions of the brain devoted to memory and higher mental functioning. Important abnormalities have specifically been observed during biopsies:

Twisted nerve cell fibers, known as neurofibrillary tangles
A sticky protein, beta amyloid

Other factors also play a role.

Click the icon to see an animation about Alzheimer's disease.

The Effects of Neurofibrillary Tangles and Beta Amyloid in Alzheimer's Disease. These biologic factors appear to be involved in the development Alzheimer's disease in the following ways:

Neurofibrillary tangles are the damaged remains of microtubules, the support structure that allows the flow of nutrients through the neurons (nerve cells). A key component in these tangled fibers is an abnormal form of the tau protein, which in its healthy version helps in the assembly of the microtubule structure. The defective tau, however, appears to block the actions of the normal version.
Beta Amyloid (also called A beta) is the second significant finding. This insoluble protein accumulates and forms sticky patches called neuritic plaque, which are found surrounded by the debris of dying nerve cells in the brains of Alzheimer's victims.
Amyloid precursor protein (APP) is a large nerve-protecting protein that is the source of beta amyloid. In Alzheimer's certain enzymes, particularly those called gamma-secretases, snip APP into beta amyloid pieces. This process is controlled by factors called presenilin proteins. (Genetic abnormalities that affect either APP or presenilin proteins occur in some inherited cases of early-onset Alzheimer's.)
High levels of beta amyloid are associated with reduced levels of the neurotransmitter acetylcholine. (Neurotransmitters are chemical messengers in the brain.) Acetylcholine is part of the cholinergic system, which is essential for memory and learning and is progressively destroyed in Alzheimer's disease.
Beta amyloid may also disrupt channels that carry sodium, potassium, and calcium. These elements serve the brain as ions, producing electric charges that must fire regularly in order for signals to pass from one nerve cell to another. If the channels that carry ions are damaged, an imbalance can interfere with nerve function and signal transmission.

Click the icon to see an image of amyloidosis.

Other Proteins. Researchers have now identified other important proteins in the areas of the brain affected by Alzheimer's disease.

ERAB (endoplasmic-reticulum associated binding protein) appears to combine with beta amyloid, which in turn attracts new beta amyloid from outside the cells. High amounts of ERAB may also enhance the nerve-destructive power of beta amyloid.
AMY plaques resemble beta amyloid so closely that researchers were able to detect them only with the use of highly sophisticated techniques.
Elevated levels of a protein called prostate apoptosis response-4 (Par-4) may cause nerve cells to self-destruct.

Researchers are also attempting to discover why beta amyloid is so toxic to nerve cells. Some researchers are focusing on two processes in the body that may be involved with Alzheimer's disease: oxidation and the inflammatory process. There is some evidence that such events can begin decades before Alzheimer's disease actually develops. One scenario for their role in Alzheimer's is as follows:

The Role of Oxidation.

As beta amyloid breaks down it releases unstable chemicals called oxygen-free radicals. Once released, oxygen-free radicals bind to other molecules through a process called oxidation.
Oxidation is the result of many common chemical processes in the body, but when oxidants are overproduced, they can cause severe damage in cells and tissue, including even affecting genetic material in cells (its DNA). Oxidation is known to play a role in many serious diseases, including coronary artery disease and cancers, and experts believe it may also contribute to Alzheimer's.

The Inflammatory Response.

One result of oxidation is the marshaling of immune factors to repair the cellular injuries it produces. Overproduction of some of these factors, however, produces the so-called inflammatory response, in which the immune process itself can actually damage the body's own cells themselves.
Principle immune cells in the brain are called macrophage/microglia (M phi). In the healthy brain, they play an important protective role against invading organisms. However, when they are activated by beta amyloid oxidation, they release toxic molecules called cytokines, which are known to cause harm. For example, significantly high levels of interleukin-6, a specific cytokine, have been detected in people with Alzheimer's.
Other inflammatory factors of specific interest in Alzheimer's research are the enzyme cyclooxygenase (COX) and its products called prostaglandins. Excess amounts of these factors may increase levels of glutamate. Glutamate is an amino acid that excites nerves and, when overproduced, is a powerful nerve-cell killer.
The inflammatory process has also been associated with the release of soluble toxins called amyloid beta-derived diffusible ligands, which some investigators believe may prove to key players in the destructive process.

Major research targets in Alzheimer's disease are the factors responsible for beta amyloid build-up and concentration in certain people and not in others. Genetic factors are believed to play a role in many cases. In 2003, the National Institute on Aging (NIA) launched the ambitious AD Genetics Initiative, a 3-year national project to bank genetic material from families who have at least two members with late-onset Alzheimer's.

The ApoE Gene and Late-Onset Alzheimer's. The major target in genetic research on late-onset Alzheimer's disease (called LOAD) has been apolipoprotein E (ApoE), which plays a role in the movement and distribution of cholesterol for repairing nerve cells during development and after injury.

The gene for ApoE comes in three major types:

ApoE4. Studies have reported the greatest deposits of beta amyloid in people with ApoE4, which is now believed to be a major risk factor for late-onset Alzheimer's. Some evidence suggests that the ApoE protein removes beta amyloid but the ApoE4 variant does so less efficiently than other ApoE types. (ApoE4 has also been studied for years as a risk factor for heart disease.)
ApoE3 and ApoE2. Fewer beta amyloid deposits have been observed in people with the ApoE3, and the fewest deposits have been observed in people with ApoE2, which may actually be protective.

People inherit a copy of one type from each parent, but Alzheimer's disease is not inevitable even in people with two copies of the ApoE4 gene. Reports vary widely in estimating the extent of risk:

People without ApoE4 have an estimated risk of between 9 - 20% for developing Alzheimer's by age 85.
In people with one copy of the gene, the risk is between 25 - 60%.
In people with two copies, the risk ranges from 50 - 90%. (Only 2% of the population carries two copies of the ApoE4 gene.)

Some researchers suspect that some specific variation of the ApoE4 gene or combinations with other genes are critical for the disease, since many people who carry the ApoE4 exhibit no signs of Alzheimer's. For example, evidence suggests that genetic factors play a role in a common subtype of late-onset Alzheimer's disease that also includes psychosis. An important 2002 genetic study has identified certain genetic linkages associated with ApoE4 that appear to play a strong role in this subtype.

Other Genetic Factors in Late-Onset Alzheimer's. Most people with late-onset Alzheimer's disease do not carry the ApoE4 gene. Increasingly, researchers believe that many cases of late-onset Alzheimer's result from a combination of genetic factors that participate in the process of producing or degrading beta amyloid. Some under investigation include:

Researchers are targeting chromosomes 9, 10, and 12 as possible locations for genetic factors involved with Alzheimer's disease. (The ApoE4 gene is on chromosome 19.) In 2005, researchers announced that mutations linked to the ubiquilin 1 (UBQLN1) gene, located on chromosome 9, might be associated with increased risk for late-onset Alzheimer's disease.
Researchers have detected mutations in the proteins amyloid precursor protein (APP) and ubiquitin-B (Ubi-B), which may account for some cases of late- and early-onset Alzheimer's. Such mutations are not inherited, however, but appear to be genetic mistakes that occur during transcription, the coding process in which DNA establishes the pattern for the production of its proteins and other molecules.
In 2007, researchers identified mutations in the SORL1 gene as a possible factor in late-onset Alzheimer’s disease. Researchers think that variations in this gene may contribute to amyloid plaque formation in Alzheimer’s disease.

Genetic Factors for Early-Onset Alzheimer's. Scientists are coming closer to identifying defective genes responsible for early-onset Alzheimer's, an uncommon, but extremely aggressive form of the disease.

Mutations in genes known as presenilin-1 (PS1) and presenilin-2 (PS2) account for most cases of early-onset inherited Alzheimer's disease. The defective genes appear to accelerate beta amyloid plaque formation and apoptosis, a natural process by which cells self-destruct.
Genetic mutations in the genes that control amyloid precursor protein (APP) are also being targeted as causes of early-onset Alzheimer's. The genetic disease Down syndrome, for example, overproduces beta-amyloid precursor protein (APP), the source of beta amyloid, and almost always leads to early Alzheimer's. Other APP mutations are being identified.

Researchers are also investigating environmental factors (infections, metals, industrial and other toxins) that may trigger oxidation, inflammation, and the disease process, particularly in people with a genetic susceptibility to Alzheimer's.

Infectious Organisms. Slow, infectious viruses cause a number of other degenerative neurologic diseases, such as kuru and Creutzfeldt-Jakob disease.

Click the icon to see an image of Creutzfeldt-Jakob disease.

Although no specific virus has been linked to Alzheimer's, some researchers theorize that people with a genetic susceptibility to Alzheimer's may be vulnerable to the actions of certain viruses, particularly under circumstances when the immune system may be weakened.

Metals. Some laboratory studies have reported excessive amounts of metal ions such as zinc, copper in the brain of people with Alzheimer's disease. Such ions may possibly change the chemical architecture of normal beta amyloid, making it more harmful. A mildly acidic environment appears to be important in the process that binds these metals to beta amyloid. Experts observe that such conditions (acidic environment and higher levels of zinc and copper) commonly occur as part of the inflammatory response to local injury.

Electromagnetic Fields. Some studies on people exposed to intense electromagnetic fields (EMF) have reported a higher incidence of Alzheimer's. However, the association between EMF and Alzheimer's is very weak.

Risk Factors

Alzheimer's disease is the seventh leading cause of death in American adults. It affects about 5 million Americans and 8 million more people worldwide. According to the U.S. Alzheimer’s Association, 1 in 8 people age 65 and older, and nearly 1 in 2 people over age 85, have Alzheimer’s disease.

Age is the greatest risk factor for Alzheimer's disease. The number of cases of Alzheimer's disease doubles every 5 years in people over 65. By age 85, almost half of all people are afflicted. People with the disease survive, on average, half as long as similarly aged adults without the disease.

With the increasing numbers of aging adults, unless effective methods for prevention and treatment are developed, Alzheimer's disease will reach epidemic proportions, afflicting about 16 million Americans within 50 years. Evidence points to older age, high blood pressure, cholesterol levels, and a family history of the disease as the most important risk factors for Alzheimer's disease.

Several studies have reported that women have a much higher risk for Alzheimer's disease than men. If there is a gender difference, it is likely to be due estrogen, the primary female hormone, which appears to have properties that protect against the memory loss and lower mental functioning associated with normal aging. Such actions include blocking production of beta amyloid, offering antioxidant protection, and regulating blood sugar (glucose) levels in the brain. The drop in estrogen levels after menopause may explain a higher risk for Alzheimer's disease in older women than in men. (Testosterone, the male hormone, converts to estrogen, which may help protect men.) Studies have been mixed, however, on the association between the decline in natural estrogen levels and mental functioning in older women.

People with a family history of the disease are at higher than average risk for Alzheimer's disease. Researchers are identifying important genetic factors, notably the ApoE4 gene, that may be responsible for late- and early-onset cases.

Dietary and other cultural factors that increase the risk for hypertension and unhealthy cholesterol levels may also play a role. For example, a study of Japanese men showed that their risk increased if they emigrated to America. And the disease is much less common in West Africa than in African-Americans, who share the same or higher risk with Caucasians in America.

High blood pressure and unhealthy cholesterol levels -- the same important risk factors for heart disease and stroke -- may also be risk factors for Alzheimer's disease. In fact, they appear to be more important than ApoE4, the genetic factor most commonly associated with Alzheimer's disease.

Blood pressure is the force applied against the walls of the arteries as the heart pumps blood through the body. The pressure is determined by the force and amount of blood pumped and the size and flexibility of the arteries.

High Blood Pressure. Studies have reported an association between Alzheimer's disease and systolic hypertension (the higher and first number in blood pressure measurement). High blood pressure can cause problems with the vascular system, which is responsible for delivering blood to the brain. Recent research suggests that some types of blood pressure medication may lower Alzheimer's risk.

High Cholesterol Levels. Research indicates an association between high cholesterol levels and Alzheimer's disease in some people. One theory is that cholesterol regulates the processing and accumulation of amyloid beta-protein.

Click the icon to see an image of cholesterol.

Stroke. High blood pressure and heart disease can increase the risk for stroke. For people who have Alzheimer’s disease or mild cognitive impairment, stroke can increase the decline of cognitive function and accelerate dementia.

Diabetes. Patients with diabetes often have high blood pressure, lipid imbalances, and circulatory disorders that affect the heart and vascular system, which in turn increases the risk for Alzheimer’s. In patients who do not have other risk factors for Alzheimer’s, diabetes itself may increase risk. Research also suggests that diabetes can increase the risk for mild cognitive impairment, a condition that often precedes Alzheimer’s disease.

High Homocysteine Levels. Homocysteine is an amino acid that has been identified as a modest risk factor in heart disease. It has also been associated with a higher risk for Alzheimer's disease. High levels are general due to deficiencies of the B vitamins B6, B12, and folate. Such vitamins are also related to nerve protection. Researchers theorize that homocysteine impairs the ability of DNA to repair nerve cells. The weakened cells are then more vulnerable to the harmful effects of oxidized beta amyloid.

Nearly all patients who inherit Down syndrome develop changes in the brain that resemble Alzheimer's if they live into their 40s, although onset varies and can occur as late as age 70. Women under the age of 35, but not older mothers, who give birth to children with Down syndrome are also at much higher risk for Alzheimer's.

Lower Education and Economic Groups. A number of studies have reported either a higher risk for Alzheimer's disease in people with less education or a lower risk for Alzheimer's disease in those who remain mentally active. Some experts speculate that learning itself may stimulate more neurons to grow and thus create a larger reserve in the brain so that it takes longer for brain cells to be destroyed. Some evidence suggests that early malnutrition, which is more likely to occur in lower income and educational groups, has been associated with smaller brains and with Alzheimer's disease in old age. Low-birth weight can cause problems in growth factors that could affect both mental and physical health later on in adulthood.

Small Head Size. The size of the skull is fixed by age 7. Brain size approximates the head size until old age, when it begins to shrink. Some evidence has reported an association between small head size (and therefore less brain volume) and Alzheimer's disease, possibly because people who start with larger brains can sustain more injury over time. For example, a 2002 study indicated that it was reduction in overall brain volume, not specific regions, that contributed to mental impairment in older healthy adults. Another study reported that people who had small heads plus the ApoE4 gene had 14 times the risk for Alzheimer's disease than those without this combination. Nevertheless, other studies have found no association between a small head size and Alzheimer's disease.

Some experts suggest that the relationship observed in other research may simply be due to social and economic factors, such as malnutrition or low birth weight, which have been associated with both Alzheimer's disease and small head size. Small head size independent of other factors, they argue, does not pose a higher risk for either Alzheimer's disease or low intelligence

Depression. There is a significant overlap between depression and dementia in the elderly. In fact depression itself is often an early symptom of Alzheimer's disease. In a 2002 study of Catholic nuns, for each of four depressive symptoms, the risk for developing Alzheimer's disease increased by an additional 19%. For example, for a woman with four depressive symptoms the risk increased by 76%. Some evidence suggests that there may even be common genetic factors in people who have both early depression and Alzheimer's disease.

Head Injury. Some studies have found an association between serious head injuries in early adulthood and the development of Alzheimer's. It is not yet known if such injuries directly cause Alzheimer's or simply accelerate the disease in people who are already susceptible to it.

Prevention

Although there is no strong evidence that any lifestyle change can prevent Alzheimer's disease, studies suggest that certain behaviors may help protect against mental decline. In particular, medications and lifestyle choices that protect the heart may be of specific importance. Various preventive drugs are under investigation, including antioxidant and anti-inflammatory therapies.

In 2004, the National Institutes of Health (NIH) halted a large clinical trial that was investigating the use of anti-inflammatory drugs in preventing Alzheimer's disease. While prior data had confirmed that NSAIDs were not effective in treating AD, research continued to explore these drugs' potential preventive benefits.

The Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT) was launched in 2001 to investigate whether long-term use of naproxen (Aleve) or celecoxib (Celebrex) could decrease the risk of developing AD. The trial was based on the premise that because inflammation is known to be involved in the process of Alzheimer’s disease, anti-inflammatory drugs may help to prevent it. The NIH suspended this trial due to evidence that the NSAID naproxen was associated with increased incidence of cardiovascular and cerebrovascular events among participants. No adverse effects appeared during this trial for the COX-2 inhibitor celecoxib. However, heart safety concerns about this drug had been raised in other trials, and investigators did not believe that celecoxib's potential benefits outweighed its risks.

Since 2004, the ADAPT investigators have continued to monitor the trial’s participants to see if these treatments had any effect in changing their risk for Alzheimer’s. In an update analysis of ADAPT data published in 2007, the researchers announced that neither naproxen nor celecoxib appear to reduce the risk for Alzheimer’s.

The same lifestyle and medical choices that reduce risk factors for heart disease and diabetes are important for reducing the risk for Alzheimer's disease. And, experts believe that treating high blood pressure and diabetes may help slow the progression of Alzheimer’s disease. The following are some heart-protective medications that may also protect the brain.

Blood Pressure Drugs. Because high blood pressure is associated with increased risk of Alzheimer’s, researchers have been studying whether blood pressure medication can reduce this risk. In a 2006 study of patients who took high blood pressure drugs, researchers found that potassium-sparing diuretics reduced the risk of developing Alzheimer’s by 70%. Beta-blockers and certain calcium channel blockers also helped to a lesser extent. ACE inhibitors appeared to offer no protection.

Statins. Statins are common drugs used to lower cholesterol levels. In past years, a number of studies reported a significantly lower risk for Alzheimer's disease in patients who took statins. However, newer studies have failed to prove that statins can help prevent Alzheimer's disease. In these recent studies, large numbers of elderly people had their dementia evaluated at baseline and then monitored over several years. The results indicated that statin use did not predict onset of AD. In the meantime, the NIH is conducting a clinical trial to investigate whether simvastatin can slow the progression of AD.

Hormone Replacement Therapy. Hormone replacement therapy (HRT) has been studied for years for health effects after menopause, including its effect on mental decline. A number of studies, including a major 2003 analysis, have found no differences in mental performance and no protection from Alzheimer's disease in women taking HRT compared to non-users. The 2003 trial, called the Women's Health Initiative Memory Study (WHIMS), enrolled 4,500 women over 65 years of age. The WHIMS study showed that older postmenopausal women who took combination HRT (estrogen plus progestin) had twice the risk of developing dementia than similarly aged women who received placebo pills. In addition to increasing the risk for dementia (including Alzheimer's disease), combination HRT failed to prevent the development of mild cognitive impairment. Based on these results, the researchers from the National Institute on Aging (NIA) recommended against prescribing combination hormone therapy to older women for maintaining or improving cognitive function. The NIA continued to research whether estrogen-only therapy could prevent or delay the onset of Alzheimer's disease. Results released in 2004 indicated that women ages 65 years and older who took estrogen-only HRT had a slightly increased risk of developing dementia.

Testosterone. Some testosterone converts to estrogen, which may be why older men appear to have a lower risk for Alzheimer's disease than older women. Animal studies have suggested that testosterone may help reduce levels of beta amyloid. There is also some evidence that low testosterone levels may be a particular risk factor in men with the ApoE4 gene. Some experts believe that giving testosterone to elderly men, and combinations of testosterone and estrogen to older women, may prove to be protective. Side effects of testosterone in women include increased body hair, acne, fluid retention, anxiety, and depression. Long term benefits or serious adverse effects are unknown.

DHEA. Dehydroepiandrosterone (DHEA) is a male-like hormone in the body that declines with age. Some evidence suggests that it may help reduce mental decline in older women, but not in older men. Studies are under way. The hormone may, however, reduce HDL (the so-called good cholesterol) when taken in higher doses. While its effect on cancer-cell growth is unknown, some evidence indicates that high levels may increase cancer risk. In any case, DHEA is not regulated, and brands vary widely in their content.

Because Alzheimer's disease rates vary among different populations, investigators are researching how diet can help in prevention. Caloric intake itself may play a role in brain health. In one study on animals, restricting calories below normal (but above starvation levels) helped prevent age-related nerve degeneration. However, in patients with existing Alzheimer's, weight loss is a strong indicator of mental decline.

Fats and Oils. Some studies suggest an association between fat and Alzheimer's disease:

In China and Nigeria, where fat intake is low, the risk of developing Alzheimer's is 1% at age of 65 compared to 5% in the U.S.
A study in the Netherlands reported an association between dementia and diets high in total fat, saturated fat, and cholesterol.
A number of studies suggest that a high-fat high-calorie diet in people who carry the ApoE4 gene may confer a particularly high risk. For example, in one study, adults who carried the ApoE4 gene and whose diet consisted of 40% fat calories had 29 times the risk for Alzheimer's compared to non-ApoE4 carriers on the same high-fat diet.

The recommended dietary goal is to limit total fat intake to 25 - 35% of total daily calories. But not all fats are alike. Unhealthy fats include saturated fats (contained in animal products such as meat) and trans-fatty acids (contained in fast foods and commercially baked products). The American Heart Association recommends limiting saturated fat intake to less than 7% of total daily calories and trans-fatty acid intake to less than 1% of total daily calories.

It is best to replace saturated fats and trans-fatty acids with unsaturated fats from plant and fish oils. Omega-3 fatty acids are excellent sources of unsaturated fats. Plant sources of omega-3 fatty acids include canola oil, soybeans, flaxseed, and certain types of nuts such as walnuts. For fish sources, salmon, mackerel, sardines, lake trout, herring, and albacore tuna are especially high in marine omega-3 fatty acids. For heart health, and possibly brain health, experts recommend eating these types of fish at least twice a week.

Two types of omega-3 fatty acids are found in fish oils: Docosahexaenoic acid (DHA) and eicosapentaneoic acid (EPA). Researchers are particularly interested in the role that DHA may play in Alzheimer’s disease prevention. DHA has been linked to many brain cell functions, and appears to have particular importance for aging brains. Studies indicate that people who have higher blood levels of DHA have a much lower risk of developing dementia and Alzheimer’s disease.

Although evidence suggests that consuming DHA-rich foods later in life helps to increase DHA levels in the brain, it is unclear whether dietary supplements can provide similar benefits. A 2007 study indicated that omega-3 fatty acid supplements may help slow cognitive decline in some patients with very mild Alzheimer’s disease, but that the supplements have little effect for advanced stages of the disease. In 2007, the U.S. National Institutes of Health launched a large-scale clinical trial to evaluate whether DHA supplements can slow the progression of cognitive and functional decline in people with mild-to-moderate Alzheimer’s disease.

Mediterranean diet is an eating plan that has specific heart-health benefits. It is rich in fiber and nutrients, including omega-3 fatty acids and antioxidant vitamins. The diet emphasizes fish, fruits, vegetables, and monounsaturated (“good”) fats, particularly olive and canola oils. A 2006 study suggested that the Mediterranean diet may also be good for the brain. In the study, patients who strictly followed the diet had a 40% lower risk of developing Alzheimer’s disease than patients who ate a conventional American diet. Other studies also indicate the Mediterranean diet is associated with a lower risk for Alzheimer’s.

Omega-3 fatty acids, found plentifully in oily fish and flaxseed and canola oils, are beneficial to people afflicted with IBD (inflammatory bowel disease).

Fruits and Vegetables. According to several studies, eating plenty of darkly colored fruits and vegetables may slow brain aging. Blueberries, which are very rich in antioxidants, are of particular interest. A 2006 study of over 3,000 elderly adults found that consumption of vegetables (especially green leafy vegetables) helped reduce the rate of cognitive decline, but fruit intake had no effect.

Alcohol. Some studies have suggested that moderate intake of alcohol (one or two drinks a day) may protect the aging brain, possibly by releasing acetylcholine, the chemical in the brain that is deficient in Alzheimer's disease. Not all studies have been positive. In any case, heavy alcohol consumption offers no protection and is dangerous.

Folate and Vitamin B12. Some studies suggest that deficiencies of vitamins B6, B12, and folate (folic acid) may be a risk factor for Alzheimer' diseases. Deficiencies in these vitamins can increase homocysteine levels, which some research associates with a higher risk for Alzheimer's disease. Foods containing folate include avocados, bananas, oranges, asparagus, green leafy vegetables, and dried beans. In the United States and some other countries, grain and cereal products are fortified with folate. B12 is found only in animal, dairy, and fish products. B6 is found in a variety of foods, including fortified cereals, beans, meat, fish, and some fruits and vegetables.

Click the icon to see an image of vitamin B12 sources.

Click the icon to see an image of folate sources.

Research is still inconclusive and conflicting about whether increased consumption of folate, through food or dietary supplements, can help prevent Alzheimer’s disease or slow its progression. A small 2006 study of healthy older adults, published in the New England Journal of Medicine, found that supplements containing folate, vitamin B12, and vitamin B6 did not help improve cognitive performance. A 2007 Lancet study indicated that folic acid supplements may help slow cognitive decline. People in the Lancet study took 800 mcg of folic acid daily, which is twice the recommended daily allowance of 400 mcg. However, this study was conducted in the Netherlands, where people tend to get less folate in their daily diets than in the United States.

Another 2007 study found that elderly people who consumed folate from both diet and supplement sources had a reduced risk for Alzheimer’s disease. Neither diet alone nor supplements alone affected Alzheimer’s risk; only the combination of the two produced an effect. The study also indicated that vitamins B6 and B12 do not affect Alzheimer’s risk.

Antioxidant Supplements. Much research on Alzheimer's disease has indicated that oxidation (release of damaging unstable particles) may play an important role in the disease process. Some reports, including a large 2002 population study, have suggested that vitamin E intake, from food or supplements, may protect against mental decline. Other studies suggest that vitamin E protects only those who carried the ApoE4 gene. Most of the evidence finding any benefits from other antioxidants comes from using a combination of antioxidant vitamins, such as vitamins C and E, but not from using them separately. However, there is no strong evidence of protection to date from using antioxidant supplements.

Physical Exercise. Studies indicate that exercise may help prevent the development of Alzheimer’s disease and other forms of dementia. A 2006 study found that older adults (65 years and older) who exercised three times a week reduced their risk for Alzheimer’s by about 40%. Exercise in the study included walking, hiking, aerobics, calisthenics, swimming, water aerobics, weight training, and stretching.

Mental Exercise. Cognitive training that includes exercises to stimulate memory, reasoning, and mental processing speed may help improve both mental ability and daily functioning. In an important 2006 study in the Journal of the American Mental Association, older community-dwelling adults who received cognitive training showed reductions in cognitive decline. In addition, they were better able to handle daily living tasks -- such as performing housework, managing money, and preparing meals -- than people who did not receive the training. The benefits of cognitive training lasted for up to 5 years afterwards. Other studies indicate that participating in intellectually engaging activity -- such as doing crossword puzzles or learning a new language -- may help reduce the risk of Alzheimer’s disease.

Social Interaction. Social interaction is also important for maintaining emotional health as well as keeping the mind active and energized. A 2007 study indicated that adults who are lonely have twice the risk of developing Alzheimer’s dementia as those who are not socially isolated.

Symptoms

The early symptoms of Alzheimer's disease (AD) may be overlooked because they resemble signs of natural aging. Older adults who begin to notice a persistent mild memory loss of recent events may have a condition called mild cognitive impairment (MCI). MCI is now believed to be a significant sign of early-stage Alzheimer's in older people. Studies now suggest that older individuals who experience such mild memory abnormalities can later develop Alzheimer's disease.

Early symptoms of Alzheimer's disease may include:

Forgetfulness (particularly of recent events or information)
Loss of concentration (having trouble planning or completing familiar tasks, difficulty with abstract thinking such as simple arithmetic problems)
Language problems (forgetting the names of objects, mixing up words, difficulty completing sentences)
Confusion about time and place (difficulty recognizing familiar neighborhoods or remembering how you arrived at a location, confusion about months or seasons )
Impaired judgment (dressing inappropriately or making poor financial decisions)
Impaired movement and coordination (slowing of movements, halting gait, reduced sense of balance)
Mood and behavior changes (rapid mood swings, emotional outbursts, personality changes, increased fear or suspicion)
Apathy and depression (loss of interest in activities, increased sleeping, sitting in front of the television for long periods of time)

Diagnosis

A definitive test to diagnose Alzheimer's disease, even in patients showing signs of dementia, has not yet been developed. A number of expert groups have developed criteria to help diagnose Alzheimer's disease and rule out other disorders. A diagnosis often involves answering questions about the patient:

Do psychological tests indicate dementia?
Does the patient have deficits in two or more areas of mental functioning (such as language, motor skills, and perceptions)?
Has memory and mental functions gotten progressively worse?
Is consciousness disturbed? (It is not in Alzheimer's disease.)
Is the patient over age 40?
Are other medical or physical conditions present that could account for the same symptoms?
Are daily activity impaired or has the behavior changed?
Is there a family history of Alzheimer's disease?
Are there other symptoms, such as depression, insomnia, incontinence, delusions, hallucinations, dramatic verbal, emotional or physical outbursts, sexual disorders, and weight loss?

Other steps involved in making a decision include laboratory tests (EEG and possibly tests to rule out other diseases) and psychological testing to determine the presence of dementia.

Although some memory impairment occurs in many people as they age, only some of these people develop Alzheimer's disease. Many similar symptoms can occur in healthy older individuals from other conditions associated with aging:

Fatigue
Grief or depression
Illness
Vision or hearing loss
The use of alcohol or certain medications
Simply the burden of too many details to remember at once

The first step in diagnosing Alzheimer's disease is to rule out other conditions that might cause memory loss or dementia. There are a number of causes for dementia in the elderly besides Alzheimer's disease:

Vascular dementia (abnormalities in the vessels that carry blood to the brain)
Lewy bodies variant (LBV), also called dementia with Lewy bodies
Parkinson's disease
Frontotemporal dementia

Experts believe that 60% of cases of dementia are due to Alzheimer's, 15% to vascular injuries, and the rest are a mixture of the two or caused by other factors.

Vascular Dementia. Vascular dementia is primarily caused by either multi-infarct dementia (multiple small strokes) or Binswanger's disease (which affects tiny arteries in the midbrain). One major analysis suggested that patients with vascular dementia have better long-term verbal memory than patients with Alzheimer's disease, but poorer executive function (less ability to integrate and organize).

Lewy Bodies Variant. Lewy bodies are abnormalities found in the brains of patients with both Parkinson's disease and Alzheimer's. They can also be present in the absence of either disease; in such cases, the condition is called Lewy bodies variant (LBV). In all cases, the presence of Lewy bodies is highly associated with dementia. LBV was defined in 1997, and some experts believe it may be responsible for about 20% of people who have been diagnosed with Alzheimer's. They can be difficult to distinguish. Compared to Alzheimer's disease patients, those with LBV may be more likely to have hallucinations and delusions early on, to walk with a stoop (similar to Parkinson's disease), to have more fluctuating attention problems, and to perform better than Alzheimer's disease patients on verbal recall but less well with organizing objects.

Parkinson's Disease. Dementia is about six times more common in the elderly Parkinson patient than in the average older adult. It is most likely to occur in older patients who have had major depression. Unlike in Alzheimer's, language is not usually affected in Parkinson's related dementia. Visual hallucinations occur in about a third of people on long-term medications.

Parkinson's disease is a slowly progressive disorder that affects movement, muscle control, and balance. Part of the disease process develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell mass known as the substantia nigra. Nerve cells in the substantia nigra send out fibers to tissue located in both sides of the brain. There the cells release essential neurotransmitters that help control movement and coordination.

Frontotemporal Dementia (FTD). Once considered rare, FTD is now considered to be the second most common cause of early-onset dementia. People who develop this condition tend to be in their mid-fifties although it can develop later on. It results in greater behavioral impairment (apathy, reduced empathy, poor self-care, unrestrained behavior) than with Alzheimer's disease. It may also be marked by speech problems and early incontinence. Brain imaging scans can help diagnose this problem.

Other Conditions that Cause Similar Symptoms. Some elderly people have a condition called mild cognitive impairment, which involves more severe memory loss than normal but no other symptoms of Alzheimer's. A number of conditions, including many medications, can produce symptoms similar to Alzheimer's:

Severe depression
Drug abuse
Thyroid disease
Severe vitamin B12 deficiency
Blood clots
Hydrocephalus (excessive accumulation of spinal fluid in the brain)
Syphilis
Huntington's disease
Creutzfeldt-Jakob disease
Brain tumors

It is important that the doctor recognize any treatable conditions that might be causing symptoms or worsening existing dementia caused by Alzheimer's or vascular abnormalities.

A number of psychological tests are used or being developed to assess difficulties in attention, perception, and memory and problem-solving, social, and language skills. Experts are researching specific tests that may help identify early on people with mild memory impairment who are at high risk for Alzheimer's disease.

Two commonly used tests that are very useful in identifying individuals who may be at risk for Alzheimer's are the Mini-Mental State Exam (MMSE) and the Mattis Dementia Rating Scale. Still, these tests have limitations.
A clock drawing test is also a good test for Alzheimer's disease. The patient is given a piece of paper with a circle on it and is first asked to write the numbers in the face of a clock and then to show "10 minutes after 11." The score is based on spacing between the numbers and the positions of the hands.

Electroencephalography (EEG) traces brain-wave activity; in some patients with Alzheimer's disease this test reveals "slow waves." EEG data helps distinguish a potential patient with Alzheimer's disease from a patient with severe depression, whose brain waves are normal.

Imaging tests include magnetic resonance imaging (MRI), positron-emission tomography (PET), and single photon emission computed tomography (SPECT). These tests are sometimes used to rule out other disorders, such as multi-infarct dementia, stroke, blood clots, and tumors. Research is being conducted to determine if these tests can help to confirm a diagnosis of Alzheimer's disease and improve understanding of disease progression. Researchers hope that imaging tests may also be able to provide diagnoses of Alzheimer’s disease while it is still in its early stages.

In 2006, scientists developed a new imaging molecule called FDDNP that they hope will enable earlier detection of Alzheimer’s disease. Research also continues on Pittsburgh compound B, a tracer molecule used in PET brain scans to highlight beta-amyloid protein deposits. Results from all this research may help to define potential drug targets and aid in the development of new Alzheimer's drugs.

Click the icon to see an image of an MRI of the brain.

In 2005, the National Institute of Aging, in collaboration with industry partners, launched the $60 million Alzheimer's Disease Neuroimaging Initiative (ADNI). This landmark 5-year clinical trial, which will be conducted at 50 sites throughout the United States and Canada, will investigate whether neuroimaging techniques, such as MRI and PET scans, can be combined with biomarkers and neuropsychological tests to measure the progression of AD and mild cognitive impairment. In 2004, the U.S. Medicare system expanded insurance coverage of PET scans for eligible beneficiaries who meet specific diagnostic criteria for both Alzheimer's disease and fronto-temporal dementia. Medicare also covers the costs for patients enrolled in its agency-approved imaging clinical trials.

Blood Tests. Blood tests are currently used to check for anemia and other disorders that can produce dementia symptoms. Investigators are researching serum biomarkers, such as the iron transport protein p97, that might help detect the presence of Alzheimer's disease.

Cerebrospinal Fluid Test. Scientists are developing new nanotechnology screening methods that may eventually be used to identify Alzheimer's disease while it is still in its earliest stages and before plaque deposits accumulate. In 2005, a research team announced it had used a bio-barcode assay to detect tiny amounts of a protein called amyloid-beta-derived diffusable ligand (ADDL) in cerebrospinal fluid. ADDLs may be involved in cognitive decline and are a potential biomarker for early stage Alzheimer's disease. Tests for other proteins are also being developed.

Odor Test. Investigators are also using the impairment of smell in Alzheimer's disease to develop tests that require patients to distinguish between odors.

Once a diagnosis has been made, some experts observe that certain factors at the time of diagnosis indicate a higher risk for a more rapid decline:

Older age
Being male
The presence of high blood pressure
Signs of loss of motor control and coordination
Tremor
Social withdrawal
Loss of appetite and severe weight loss
Accompanying sensory problems, such as hearing loss and a decline in reading ability
General physical debility

Medications

Most drugs used to treat Alzheimer's, and those under investigation, are aimed at slowing progression. There are no cures to date. In addition, the improvements from some of these drugs may be so modest that even the patients and their families are not aware of them. Even in these cases, however, the drugs may delay the need for admission to nursing homes.

There are currently two drug classes that have been approved by the U.S. Food and Drug Administration (FDA) to treat the cognitive symptoms of Alzheimer's disease:

Cholinesterase inhibitors (generally used to treat mild-to-moderate Alzheimer's; donepezil is also approved for treatment of severe dementia )
N-methyl-D-aspartate (NMDA) receptor antagonists (used to treat moderate-to-severe Alzheimer's)

Cholinesterase inhibitors are designed to protect the cholinergic system, which is essential for memory and learning and is progressively destroyed in Alzheimer's. These drugs work by preventing the breakdown of the brain chemical acetylcholine and are recommended for the treatment of mild-to-moderate Alzheimer's. The first cholinesterase inhibitor, tacrine, was approved in 1993 but is rarely prescribed today due to safety concerns. The three most commonly prescribed cholinesterase inhibitors are donepezil (approved in 1996), rivastigmine (approved in 2000), and galantamine (approved in 2001).

Cholinesterase inhibitors may increase the risk for gastrointestinal bleeding or ulcers, and patients should be cautious about using these medicines with NSAIDs (which can also cause gastric irritation). Common side effects of cholinesterase inhibitors, especially when taken at higher doses, may include nausea, vomiting, diarrhea, and upset stomach.

Donepezil. Donepezil (Aricept) is the only Alzheimer’s drug approved for all stages of dementia, from mild to severe. It is taken once a day and has only modest benefits, but it does help slow loss of function and reduce caregiver burden. It works equally in patients with or without the ApoE4 gene. Several trials, including an important 2005 New England Journal of Medicine (NEJM) study, have found that donepezil may have short-term benefits for patients with mild cognitive impairment by delaying progression to AD. In the NEJM study, donepezil slowed progression during the first year of therapy, but demonstrated no benefits by the conclusion of the 3-year trial. Studies also suggest that donepezil may help improve behavior and memory in patients with moderate-to-severe Alzheimer’s when it is given in combination with memantine (Namenda).
Rivastigmine. Rivastigmine (Exelon) targets two enzymes: Acetylcholinesterase and butyrylcholinesterase. It is taken as a pill twice a day. (The FDA approved a skin patch version of the drug in 2007.) Rivastigmine may be particularly helpful for patients with rapidly progressing disease. It has slowed or slightly improved disease status even in patients with advanced disease. Rivastigmine may cause significantly more side effects than donepezil, including nausea, vomiting, and headache.
Galantamine (Razadyne). Galantamine not only protects the cholinergic system but also acts on nicotine receptors, which are also depleted during Alzheimer's. Studies report that it improves daily living, behavior, and mental functioning, including in patients with mild to advanced-moderate Alzheimer's disease and those with a mix of Alzheimer's disease and vascular dementia. Some studies have suggested that the effects of galantamine may persist for a year or longer and even strengthen over time. In 2005, the name of galantamine was changed from Reminyl to Razadyne.
Tacrine. Tacrine (Cognex) was the first cholinergic protective drug. It needs to be taken four times a day, has only modest benefits, and has no benefits for patients who carry the ApoE4 gene. In high doses, it can also injure the liver. In general, newer cholinergic protective drugs that do not pose as great a risk for the liver are now used for Alzheimer's.

About half of patients with mild-to-moderate disease show slight improvement with these drugs. Comparative studies have reported little differences in effectiveness among them. All drugs have gastrointestinal side effects, including nausea. Of note, some of the drugs often used in elderly Alzheimer's disease patients are known as anticholinergics and may offset the effects of the Alzheimer's disease pro-cholinergic drugs. Such drugs include antihistamines, antipsychotic drugs, and some anti-incontinence drugs.

In any case, the benefits of these drugs are far from dramatic. In fact, many experts have reservations about developing any additional drugs that affect the cholinergic system since, at best, they only slow progression and do not appear to affect the basic destructive disease process. When patients go off the drugs, the deterioration continues. In 2005, the United Kingdom’s National Institute for Clinical Excellence (NICE) recommended against the use of donepezil, rivastigmine, galantamine, and memantine for Alzheimer’s disease treatment. The agency contended that the costs of these drugs outweigh their modest benefits.

Memantine (Namenda) is approved for treatment of moderate-to-severe Alzheimer’s disease. (Most cholinesterase inhibitors are used to treat mild-to-moderate stages of the disease.) By blocking NDMA receptors, memantine protects against the overstimulation of glutamate, an amino acid that excites nerves and, in excess, is a powerful nerve-cell killer.

Memantine is prescribed either alone or in combination with donepezil. Studies indicate that memantine may help improve cognitive function and delay the progression of Alzheimer’s disease for up to 1 year. Side effects are generally mild but may include dizziness, drowsiness, or fainting.

In one study of effects on moderate-to-severe Alzheimer's, patients who received memantine showed a small but statistically significant benefit in cognitive function and performance of daily abilities compared with those patients who were given placebo. In a 2004 study, memantine was added to the drug regimen of patients with moderate-to-severe Alzheimer's who had taken donepezil for at least 6 months. In comparison to patients who took only donepezil, patients who received the combination donepezil-memantine therapy showed a greater improvement in measures of cognitive function, activities of daily living, and behavior parameters. A 2006 study indicated that memantine combined with donepezil may help reduce behavior problems -- such as agitation, aggression, and irritability -- and improve disturbances in appetite and eating.

Although cholinesterase inhibitors and memantine are the best available medications for Alzheimer's, their benefits are, unfortunately, quite modest. More effective methods of prevention and treatment are urgently needed.

There has been considerable controversy over whether NSAIDs may help in the treatment of Alzheimer's disease. As inflammation is involved in the destruction of brain cells, it has been suggested that anti-inflammatory drugs might be able to halt this process and thus slow the progression of the disease. In a rigorous 2003 study, patients with mild-to-moderate Alzheimer's were randomized to receive either naproxen (Aleve) or rofecoxib (Vioxx) or placebo. After 12 months of treatment, patients in the anti-inflammatory groups did not show any difference in cognitive improvement compared to those patients who received placebo.

Results from another large study, published in 2004, also failed to demonstrate improvement in cognitive function for patients with mild-to-moderate Alzheimer's who were treated with rofecoxib. Since the completion of these studies, rofecoxib was withdrawn from the market, and the NIH suspended a clinical study assessing naproxen’s preventive benefits (see Nonsteroidal Anti-Inflammatory Drugs as Prevention). As mentioned earlier, patients should be cautious about taking NSAIDs in combination with cholinesterase inhibitors as they may increase the risk of gastrointestinal bleeding.

Nicotine enhances the actions of the cholinergic system (which is depleted in Alzheimer's disease) and is known to improve concentration and memory in the short term. Some studies have suggested that nicotine may protect nerve cells and help prevent the formation of beta amyloid. One study indicated that nicotine might help protect against Alzheimer's disease in carriers, but not noncarriers, of the ApoE4 gene. Another reported improvement in verbal recall and word retrieval in healthy relatives of Alzheimer's disease patients who wore a low-dose nicotine patch. Research to date, however, has found no strong evidence of improvement in Alzheimer's disease patients with nicotine replacement methods. No one should smoke to prevent or treat Alzheimer's disease.

Manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedy or dietary supplement.

Ginkgo Biloba. Ginkgo biloba is a common herb that has antioxidant properties and appears to increase blood flow to the brain. A 2002 study of healthy people who took over-the-counter ginkgo for 6 weeks reported no improvements in memory or mental function. Studies are reporting that a ginkgo biloba extract, called Egb 761, may slightly improve the memory of patients with mild to moderate Alzheimer's disease. The herb poses a small increased risk for bleeding, which may be hazardous in combination with other blood-thinning medications, such as warfarin or high-doses of vitamin E.

Turmeric. Studies suggest that circumin, a compound found in the spice turmeric, has properties that may protect against the Alzheimer's disease process.

Melatonin. Melatonin, a natural hormone involved in sleep regulation, is of interest to researchers. It is an antioxidant, may break down beta amyloid, and is able to pass through the blood-brain barrier. Deficiencies have been observed in patients with Alzheimer's disease. A number of studies (but not all) report that melatonin may improve sleep habits in these patients. Some studies reported slower progression of mental impairment.

A number of drugs are being investigated for treatment and prevention of Alzheimer's disease. Intense areas of research are focusing on drugs that prevent beta amyloid build-up, its toxic effects on nerve cells, or other mechanisms of the disease process. Promising research in late-stage clinical trials include.

Tramiprosate (Alzhemed) is an experimental drug designed to prevent beta-amyloid accumulation in the brain.
Flurizan (MPC-7869) may help reduce amyloid plaque development. It is currently being studied in Phase III trials for adults with mild Alzheimer’s disease.
Rosiglitazone XR (Avandia) is an extended-release formulation of a drug used to treat type 2 diabetes. Its anti-inflammatory properties are being studied as a treatment for patients with mild-to-moderate Alzheimer’s who do not carry the APOE-e4 gene. Phase III results have been promising, but this drug has been linked to increased risk for heart attack deaths in patients with diabetes. In 2007, a panel of experts from the Food and Drug Administration (FDA) agreed the drug increases the risk of heart attacks -- but concluded it should remain on the market. The panel did, however, recommend the FDA require rosiglitazone's maker to add warnings to the drug's label. Patients or caregivers of patients who take rosiglitazone, especially those who have heart disease or who are at high risk for heart attack, should discuss their treatment options with their doctors.
Dimebon is an antihistamine, which researchers think may help prevent brain cell death. The drug is currently in Phase II trials.
Antioxidants such as vitamin E and selenium are being investigated for their preventive effects. Antioxidant treatment trials include curcumin (the yellow pigment found in turmeric spice) and a combination trial with fish oil and alpha-lipoic acid.

Depression. Major depression with dementia that occurs in elderly people may be an early sign of Alzheimer's. In such cases, it precedes Alzheimer's by 2 years or less. (It is, in fact, sometimes difficult to differentiate major depression from early-stage Alzheimer's disease.) Antidepressants known as selective serotonin reuptake inhibitors (SSRIs), including fluoxetine (Prozac) and sertraline (Zoloft), may be effective in relieving depression, irritability, and restlessness associated with Alzheimer's in some patients.

Apathy. Depression is often confused with apathy. An apathetic patient lacks emotions, motivation, interest, and enthusiasm while a depressed patient is generally very sad, tearful, and hopeless. According to one study, apathy is more common than depression in patients with Alzheimer's disease. It responds to stimulants, such as methylphenidate (Ritalin), rather than antidepressants.

Psychosis. Antipsychotic drugs are used to treat verbally or physically aggressive behavior and hallucinations. Because older antipsychotic drugs, such as haloperidol (Haldol), have severe side effects, most doctors now prescribe newer atypical antipsychotics, such as risperidone (Risperdal) or olanzapine (Zyprexa).

However, these newer antipsychotic drugs still can cause serious side effects, including confusion, sleepiness, and Parkinsonian-like symptoms. In addition, studies indicate that their safety risks may outweigh any possible benefits. A 2005 study showed that these drugs produce a slightly increased rate of death in patients with Alzheimer’s disease or dementia. In addition, several studies from 2006 and 2007 published in the New England Journal of Medicine suggested that atypical antipsychotics work no better than placebo in controlling psychosis, aggression, and agitation in patients with Alzheimer’s.

Most experts now recommend that doctors delay prescribing antipsychotic medication unless absolutely necessary. They recommend first trying behavioral treatments and controlling changes in the patient’s environment and routine. Anti-seizure drugs, such as carbamazepine (Tegretol) or valproate (Depakote), can also sometimes treat agitation and other psychotic symptoms. Non-drug treatments, such as bright light boxes, are also showing promise for managing psychotic and behavioral symptoms.

Disturbed Sleep. Patients with Alzheimer's disease commonly experience disturbances in their sleep/wake cycles. Moderately short-acting sleeping drugs, such as temazepam (Restoril), zolpidem (Ambien), or zaleplon (Sonata), or sedating antidepressants, such as trazodone (Desyrel, Molipaxin), may be useful in managing insomnia. Some research suggests that exposure to brighter-than-normal artificial light during the day for patients with normal vision may help reset wake/sleep cycles and prevent nighttime wandering and sleeplessness. Trials on melatonin, a natural hormone that helps trigger sleep at night, are in progress.

Stages

The lifespan of patients with Alzheimer's is generally reduced, although a patient may live anywhere from 3 - 20 years after diagnosis. The final phase of the disease may last from a few months to several years, during which time the patient becomes increasingly immobile and dysfunctional. Caregivers should understand the phases of this illness in order to help determine their own capacities for dealing with this painfully sad disease.

Telling the Patient. Often doctors will not tell patients that they have Alzheimer's. If a patient expresses a need to know the truth, it should be disclosed. Both the caregiver and the patient can then begin to address issues that can be controlled, such as access to support groups and drug research.

Mood and Emotional Behavior. Patients display abrupt mood swings, and many become aggressive and angry. Some of this erratic behavior is caused by chemical changes in the brain. But it may also be due to the experience of losing knowledge and understanding of one's surroundings, causing fear and frustration that patients can no longer express verbally.

The following recommendations for caregivers may help soothe patients and avoid agitation:

Keep environmental distractions and noise at a minimum if possible. (Even normal noises, such as people talking outside a room, may seem threatening and trigger agitation or aggression.)
Speak clearly. Most experts recommend speaking slowly to a patient with Alzheimer's disease, but some caregivers report that patients respond better to clear, quickly spoken, short sentences that they can more easily remember.
Use a combination of facial expressions, voice tones, and words for communicating emotions. (One study suggested that patients may have difficulty in recognizing the meaning of facial expressions, particularly those signaling sadness, surprise, and disgust.)
Limit choices (such as clothing selection).
Offer diversions, such as a snack or car ride, if the patient starts shouting or exhibiting other disruptive behavior.
Simply touching and talking may also help.
Maintain as natural an attitude as possible. Patients with Alzheimer's disease can be highly sensitive to the caregiver's underlying emotions and react negatively to patronization or signals of anger and frustration.
Showing movies or videos of family members and events from the patient's past may be comforting.

Although much attention is given to the negative emotions of patients with Alzheimer's disease, some patients become extremely gentle, retaining an ability to laugh at themselves or appreciate simple visual jokes even after their verbal abilities have disappeared. Some patients may seem to be in a drug-like or "mystical" state, focusing on the present experience as their past and future slip away. Encouraging and even enjoying such states may bring some comfort to a caregiver.

There is no single Alzheimer's personality, just as there is no single human personality. All patients must be treated as the individuals they continue to be, even after their social self has vanished.

Appearance and Cleanliness. For the caregiver, grooming the patient may be an alienating experience. For one thing, many patients resist bathing or taking a shower. Some spouses find that showering with their afflicted mate can solve the problem for a while. Often patients with Alzheimer's disease lose their sense of color and design and will put on odd or mismatched clothing. It is important to maintain a sense of humor and perspective and to learn which battles are worth fighting and which ones are best abandoned.

Driving. As soon as Alzheimer's is diagnosed, the patient should be prevented from driving. One study found that more than half of elderly people involved in fatal accidents had some degree of neurologic damage.

Wandering. A potentially dangerous trait is the patient's tendency to wander. At the point the patient develops this tendency, many caregivers feel it is time to seek out nursing homes or other protective institutions for their loved ones. For those who remain at home, the following precautions are recommended:

Locks should be installed outside the door, which the caregiver can open, but the patient cannot.
Alarms may be installed at exits.
A daily exercise program should be implemented, which may help tire the patient. One study showed that walking 30 minutes, three times a day, also improved communication.
The caregiver should contact organizations, such as Alzheimer's Association or Medic Alert, for identification supplies and procedures that help locate patients who wander away from home and become lost.
Some experts are discussing the benefits versus the ethics of electronic tagging, which would emit a radio signal or alarm that allows the patient to be tracked using a detector.

Speech Problems. Some evidence suggests that speech therapy combined with Alzheimer's disease medications may be helpful for maintaining verbal skills patients with mild symptoms.

Sexuality. In many cases, the patient becomes uninhibited sexually. At the same time, the patient's physical deterioration and receding capacity to recognize the spouse as a known and loved individual can make sexual activity unattractive for the caregiving spouse. Other patients may lose interest in sex. If sexual issues are a problem, they should be discussed openly with the doctor. Ways should be found to maintain non-sexual physical affection that can bring comfort to both the patient and the spouse.

Patients with Alzheimer's disease need 24-hour a day attention. Even if the caregiver has the resources to keep the patient at home during later stages of the disease, outside help is still essential. If available, home visits by a health profession can have a favorable impact on survival and delay the need for a nursing home. Medicare now covers many Alzheimer's services, and patients should be able to stay at home longer than previously.

Incontinence. A patient's incontinence is generally devastating to the caregiver and a primary reason why many caregivers decide to seek nursing home placement when the patient reaches this stage. When the patient first shows signs of incontinence, the doctor should make sure that it is not caused by an infection. Urinary incontinence may be controlled for some time by trying to monitor times of liquid intake, feeding, and urinating. Once a schedule has been established, the caregiver may be able to anticipate incontinent episodes and get the patient to the toilet before they occur.

Immobility and Pain. As the disease progresses, patients become immobile, literally forgetting how to move. Eventually, they become almost entirely wheelchair-bound or bedridden. Bedsores can be a major problem. Sheets must be kept clean, dry, and free of food. The patient's skin should be washed frequently, gently blotted thoroughly dry, and moisturizers applied. The patient should be moved every 2 hours and the feet kept raised with pillows or pads. Exercises should be administered to the legs and arms to keep them flexible.

Dehydration. Dehydration can become a problem. It is essential to encourage fluid intake equal to 8 glasses of water daily. Coffee and tea are diuretics and will deplete fluid.

Eating Problems. Weight loss and the gradual inability to swallow are two major related problems in late-stage Alzheimer's and are associated with an increased risk of death. Weight gain, however, is linked to a lower risk of dying. The patient can be fed through a feeding syringe, or the caregiver can encourage chewing action by pushing gently on the bottom of the patient's chin and on the lips. The caregiver should offer the patient foods of different consistency and flavor. Because choking is a danger, the caregiver should learn to administer the Heimlich maneuver, which may be taught by the local Red Cross. In very late stages, some caregivers choose feeding tubes for the patient. They should be aware that feeding tubes have no measurable impact on survival.

About 80% of patients with Alzheimer's disease are cared for by family members, who often lack adequate support, finances, or training for this difficult job. Few diseases disrupt patients and their families so completely or for so long a period of time as Alzheimer's. The patient's family endures two separate losses and grieves twice:

First, they must grieve for the ongoing disappearance of the personality they recognize. Dealing with the patient throughout the course of the disease is like Alice's fall down the rabbit hole into Wonderland. No sooner has the caregiver grappled with one set of problems, when the patient's further deterioration creates new and more intractable ones.
Finally, the caregiver must grieve the actual death of the person.

Often, caregivers themselves begin to show signs of mental disorder or ill health. Depression, empathy, exhaustion, guilt, and anger can play havoc with even a healthy individual faced with the care of a loved one suffering from Alzheimer's.

Fortunately, research shows that intensive support services can greatly improve caretakers’ quality of life and make it easier for them to continue caring for patients in their homes. In a 2006 study, caregivers who received individual and family counseling, telephone counseling, support groups, and stress management and problem-solving techniques reported reduced rates of depression and improved self-confidence compared with those who received only written educational materials. Another 2006 study indicated that improving caregivers’ access to counseling and support services can help delay nursing home placement of patients. National and local Alzheimer's associations can provide important support and other services.

A point comes when the most devoted caregiver will probably need to institutionalize the patient. That point is determined not only by the caregiver's emotional endurance, but also by their physical strength and stamina, as a patient typically takes on the random, undisciplined behavior of a very young child. Financial considerations in finding a nursing home are often paramount, but the kind of care is equally important. Although fully half of all nursing home patients suffer from Alzheimer's, not all nursing homes have programs specifically designed for them. Some institutions may claim that they do, but often they simply group patients together without offering any special programs. If a caregiver manages to find a facility that offers good services, it may be located far from home, making visits difficult. The caregiver must then decide whether superior care at a distant institution is worth seeing the patient less frequently. When the patient's illness becomes terminal, a hospice program may be another option.

1. Although I cannot control the disease process, I need to remember I can control many aspects of how it affects my relative.

2. I need to take care of myself so that I can continue doing the things that are most important.

3. I need to simplify my lifestyle so that my time and energy are available for things that are really important at this time.

4. I need to cultivate the gift of allowing others to help me, because caring for my relative is too big a job to be done by one person.

5. I need to take one day at a time rather than worry about what may or may not happen in the future.

6. I need to structure my day because a consistent schedule makes life easier for me and my relative.

7. I need to have a sense of humor because laughter helps to put things in a more positive perspective.

8. I need to remember that my relative is not being difficult on purpose; rather their behavior and emotions are distorted by the illness.

9. I need to focus on and enjoy what my relative can still do rather than constantly lament over what is gone.

10. I need to increasingly depend upon other relationships for love and support.

11. I need to frequently remind myself that I am doing the best that I can at this very moment.

12. I need to draw upon the Higher Power, which I believe is available to me.

Source: The American Journal of Alzheimer's Care and Related Disorders & Research, Nov/Dec 1989

Resources

www.alzheimers.org -- Alzheimer's Disease Education and Referral Center
www.alz.org -- Alzheimer's Association
www.alzforum.org -- Alzheimer's Research Forum
www.alzfdn.org -- Alzheimer's Foundation of America
www.alz.co.uk -- Alzheimer's Disease International
www.nia.nih.gov -- National Institute on Aging
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.aan.com -- American Academy of Neurology
www.medicalert.org -- Medic Alert
www.ahaf.org -- American Health Assistance Foundation
www.clinicaltrials.gov -- Find clinical trials
www.medicare.gov/NHCompare/Home.asp -- Find a nursing home

References

ADAPT Research Group, Lyketsos CG, Breitner JC, Green RC, Martin BK, Meinert C, et al. Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial. Neurology. 2007 May 22;68(21):1800-8. Epub 2007 Apr 25.

Akomolafe A, Beiser A, Meigs JB, Au R, Green RC, Farrer LA, et al. Diabetes mellitus and risk of developing Alzheimer disease: results from the Framingham Study. Arch Neurol. 2006 Nov;63(11):1551-5.

Ayalon L, Gum AM, Feliciano L, Arean PA. Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in patients with dementia: a systematic review. Arch Intern Med. 2006 Nov 13;166(20):2182-8.

Belle SH, Burgio L, Burns R, Coon D, Czaja SJ, Gallagher-Thompson D, et al. Enhancing the quality of life of dementia caregivers from different ethnic or racial groups: a randomized, controlled trial. Ann Intern Med. 2006 Nov 21;145(10):727-38.

Cummings JL, Schneider E, Tariot PN, Graham SM; Memantine MEM-MD-02 Study Group. Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment. Neurology. 2006 Jul 11;67(1):57-63.

Durga J, van Boxtel MP, Schouten EG, Kok FJ, Jolles J, Katan MB, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet. 2007 Jan 20;369(9557):208-16.

Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving G, et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol. 2006 Oct;63(10):1402-8.

Gamaldo A, Moghekar A, Kilada S, Resnick SM, Zonderman AB, O'Brien R. Effect of a clinical stroke on the risk of dementia in a prospective cohort. Neurology. 2006 Oct 24;67(:1363-9.

Luchsinger JA, Reitz C, Patel B, Tang MX, Manly JJ, Mayeux R. Relation of diabetes to mild cognitive impairment. Arch Neurol. 2007 Apr;64(4):570-5.

Luchsinger JA, Tang MX, Miller J, Green R, Mayeux R. Relation of higher folate intake to lower risk of Alzheimer disease in the elderly. Arch Neurol. 2007 Jan;64(1):86-92.

McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med. 2006 Jun 29;354(26):2764-72.

Mittelman MS, Haley WE, Clay OJ, Roth DL. Improving caregiver well-being delays nursing home placement of patients with Alzheimer disease. Neurology. 2006 Nov 14;67(9):1592-9.

Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS. Associations of vegetable and fruit consumption with age-related cognitive change. Neurology. 2006 Oct 24;67(:1370-6.

Regan C, Katona C, Walker Z, Hooper J, Donovan J, Livingston G. Relationship of vascular risk to the progression of Alzheimer disease. Neurology. 2006 Oct 24;67(:1357-62.

Rogaeva E, Meng Y, Lee JH, Gu Y, Kawarai T, Zou F, et al. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat Genet. 2007 Feb;39(2):168-77. Epub 2007 Jan 14.

Scarmeas N, Stern Y, Mayeux R, Luchsinger JA. Mediterranean diet, Alzheimer disease, and vascular mediation. Arch Neurol. 2006 Dec;63(12):1709-17. Epub 2006 Oct 9.

Schaefer EJ, Bongard V, Beiser AS, Lamon-Fava S, Robins SJ, Au R, et al. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Arch Neurol. 2006 Nov;63(11):1545-50.

Schneider JA, Arvanitakis Z, Bang W, Bennett DA. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology. 2007 Jun 13; [Epub ahead of print]

Schneider LS, Tariot PN, Dagerman KS, Davis SM, Hsiao JK, Ismail MS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med. 2006 Oct 12;355(15):1525-38.

Small GW, Kepe V, Ercoli LM, Siddarth P, Bookheimer SY, Miller KJ, et al. PET of brain amyloid and tau in mild cognitive impairment. N Engl J Med. 2006 Dec 21;355(25):2652-63.

Willis SL, Tennstedt SL, Marsiske M, Ball K, Elias J, Koepke KM, et al. Long-term effects of cognitive training on everyday functional outcomes in older adults. JAMA. 2006 Dec 20;296(23):2805-14.

Wilson RS, Krueger KR, Arnold SE, Schneider JA, Kelly JF, Barnes LL, et al. Loneliness and risk of Alzheimer disease. Arch Gen Psychiatry. 2007 Feb;64(2):234-40.

Review Date:
7/31/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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Neuralgia

admin — Wed, 03 Sep 2008 17:56:19 -0700

Overview

Definition
Alternative Names
Causes, incidence, and risk factors
Symptoms
Signs and tests
Treatment
Expectations (prognosis)
Complications
Calling your health care provider
Prevention

Illustrations

Central nervous system and peripheral nervous system

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Neuralgia is pain that follows the path of a specific nerve.

Alternative Names

Nerve pain; Postherpetic neuralgia

Causes, incidence, and risk factors

The causes of neuralgia vary. Chemical irritation, inflammation, trauma (including surgery), compression of nerves by nearby structures (for instance, tumors), and infections may all lead to neuralgia. In many cases, however, the cause is unknown.

Neuralgia is most common in elderly persons, but it may occur at any age.

Trigeminal neuralgia is the most common form of neuralgia. For information on this condition, see the article on trigeminal neuralgia.

A related but rather uncommon neuralgia affects the glossopharyngeal nerve, which provides sensation to the throat. Symptoms of this neuralgia are short, shock-like episodes of pain located in the throat.

Neuralgia may occur after infections such as shingles. Shingles-related neuralgia produces a constant burning pain after the shingles rash has healed. The pain is worsened by movement of or contact with the affected area.

Postherpetic neuralgia may be debilitating long after signs of the original herpes infection have disappeared. Other infectious diseases that may cause neuralgia are syphilis and Lyme disease.

Diabetes is another common cause of neuralgia. Diabetes damages the tiny arteries that supply circulation to the nerves, resulting in nerve fiber malfunction and sometimes nerve loss. Diabetes can produce almost any neuralgia nearly anywhere in the body, including trigeminal neuralgia.

Other medical conditions that may be associated with neuralgias include chronic renal insufficiency and porphyria -- a hereditary disease in which the body cannot rid itself of certain substances produced after the normal breakdown of blood in the body. Certain drugs may also cause neuralgia.

Symptoms

Pain located anywhere, usually on or near the surface of the body
- In the same location for each episode
- Sharp, stabbing pain or constant, burning pain
Pain along the path of a specific nerve
Impaired function of affected body part due to pain, or muscle weakness due to motor nerve damage.
Increased sensitivity of the skin or numbness of the affected skin area (feeling similar to a local anesthetic, such as a Novocaine shot)

Any touch or pressure is interpreted as pain. Movement may also be painful.

Signs and tests

Neurologic examination shows tenderness occurring along a nerve tract. Trigeminal neuralgia usually causes pain along the second and third nerve divisions (lower face and jaw), and rarely involves the first nerve division (temple and forehead). Other signs of altered nerve function may be seen often, such as loss of deep tendon reflexes, local loss of muscle bulk, local lack of sweating (sweating is regulated by nerve function), and abnormal skin sensation.

There may be specific trigger points (areas where even a slight touch triggers pain). A dental examination is used to rule out dental disorders that may cause facial pain. The presence of other symptoms (such as redness or swelling) may indicate disorders causing the pain, such as infections, bone fractures, rheumatoid arthritis, or other disorders.

No tests are specific for neuralgia, but tests may be used to rule out other causes of the pain. Sometimes a nerve conduction study with electromyography (NCS/EMG), which examines the electrical activity of nerves, may confirm the diagnosis.

The first part of the test, the NCS, involves giving small electric shocks to skin areas overlaying specific nerve paths. The physician then determines whether the conduction of electricity is delayed or blocked through the particular nerve that was tested.

The second part of the test, the EMG, involves the careful insertion of a very fine needle into the skin. The needle is attached to an electric probe. This probe measures the electrical activity of a muscle of interest at rest and during motion. EMG indirectly provides useful clues regarding nerve function. Although the procedure sounds rather unpleasant, most patients are able to tolerate it with little discomfort.

There are a number of other laboratory tests doctors use to determine the cause of neuralgia. Blood tests to check blood sugar and kidney function are routinely used. When the diagnosis is not clear, other tests may be helpful -- particularly whenever there is suspicion of an underlying medical problem like arthritis, syphilis, vitamin deficiencies, or other less common disorders. If multiple sclerosis is suspected, the diagnosis usually can be confirmed with an imaging test of the brain such as an MRI.

A lumbar puncture (spinal tap) is often used to confirm the diagnosis of multiple sclerosis and other nerve disorders. It involves taking a sample of cerebrospinal fluid (CSF). Analysis of this fluid may show evidence of inflammation, helping to establish the correct diagnosis.

Treatment

Treatment of neuralgia is aimed at reversing or controlling the cause of the nerve problem (if identified), as well as providing pain relief. Therefore, the treatment varies depending on the cause, location, and severity of the pain, and other factors. Even if the cause of the neuralgia is never identified, the condition may improve spontaneously or disappear with time.

The cause (if known) should be treated. This may include surgical removal of tumors, or surgical separation of the nerve from blood vessels or other structures that compress it. This can be the approach taken for certain cases of carpal tunnel syndrome and trigeminal neuralgia.

Strict control of blood sugar may accelerate recovery in people with diabetes who develop neuralgia.

Mild over-the-counter analgesics such as aspirin, acetaminophen, or ibuprofen may be helpful for mild pain. Narcotic analgesics such as codeine may be needed for a short time to control severe pain. These traditional pain-killers, however, often have disappointing results.

Other types of medications work in different parts of the nervous system and often provide better symptom control. For example, antiseizure medications such as carbamazepine, gabapentin, lamotrigine or phenytoin may be helpful for pain associated with trigeminal neuralgia. The most common side effects of antiseizure drugs are drowsiness, tremor, and incoordination.

Antidepressant medications, such as amitriptyline, may be helpful to control pain in some cases. The topical (local) application of creams containing capsaicin also may help to control pain.

Other treatments may include nerve blocks, local injections of anesthetic agents, or surgical procedures to decrease sensitivity of the nerve. Some procedures involve the ablation (surgical destruction) of the affected nerve using different methods, such as local radiofrequency, heat, balloon compression, and injection of chemicals (such as glycerolysis).

Unfortunately, these procedures do not guarantee improvement and can cause loss of sensation or abnormal sensations.

Another strategy sometimes used for resistant cases of neuralgia is called motor cortex stimulation (MCS), which consists of surgically placing an electrode over the sensory cortex of the brain. The electrode is hooked to a pulse generator pocketed under the skin. Such surgical procedures, however, are tried only when more conservative approaches have failed.

For some patients, post herpetic neuralgia can be treated with a combination of oral (taken by mouth) prednisone and antiviral medication.

Physical therapy may be helpful for some types of neuralgia, especially postherpetic neuralgia. Treatment of shingles with antiviral medication may decrease the incidence of postherpetic neuralgia.

Expectations (prognosis)

Most neuralgias are not life-threatening and do not indicate other life-threatening disorders. However, pain can be severe and, in some cases, incapacitating. For severe pain, be sure to see a pain specialist so that all options for treatment can be explored.

Most neuralgias will respond to treatment. Attacks of pain are usually episodic (occurring in intervals, alternating with relatively pain-free periods of time). However, attacks may become more frequent in some patients as they age.

Complications

Unnecessary dental procedures prior to diagnosis of neuralgia
Disability caused by pain
Complications of surgery
Side effects of medications used to control pain (see the specific medication)

Calling your health care provider

Call for an appointment with your health care provider if symptoms of neuralgia are present, especially if prolonged or unrelieved by over-the-counter analgesics. See a pain specialist for severe pain.

Prevention

Treatment of associated disorders such as diabetes and renal insufficiency may prevent development of some neuralgias. Strict control of blood sugar may prevent diabetic nerve damage.

Review Date: 9/7/2006

Reviewed By: Kenneth Gross, MD, Neurology, North Miami, FL. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

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