FitSugar

Women's Brains and Migraines

FitSugar — Wed, 15 Aug 2007 02:00:00 -0700

It is no secret that the female brain is different than its male counter part. It seems these differences are giving us headaches, and I mean that literally. Women are 3 times more likely to suffer from migraines. A recent study proved that it isn't all in our heads (figuratively speaking).

Advances in brain imaging technology now suggest that migraines may start as a result of brain excitability. People with migraines show dramatic waves of brain activity that spread across the surface of the brain. This activity is thought to trigger not only the severe pain associated with migraines but also the visual symptoms, dizziness, and difficulty concentrating often associated with migraines. Researchers believe many factors, like genes, hormones, and environmental triggers like stress, diet, and
changes in sleep patterns, may contribute to migraines in both sexes.

For further reading on this topic, check out the article Why Women Have More Migraines than Men at the Science Daily.

Source

Brain Bike Sharpens Your Mind, Tires Your Legs

FitSugar — Thu, 12 Feb 2009 04:30:00 -0800

Cardio is good for our hearts, muscles, and circulation, but because it's so repetitive, it can get boring fast. People help pass the time by listening to their iPods, watching TV or movies, reading magazines and books, and I've even seen someone knitting on the treadmill.

Now there's a new way to help you forget you're exercising. It's known as the NeuroActive Bike, or Brain Bike. It's a computer attached to a stationary bike, and there are 22 "brain-stimulating exercises" or games, that challenge your mind and memory. The goal is to improve your cardiovascular and cerebral health at the same time.

To see a video of how this bike works and find out how much one costs, read more.

They are already showing up in gyms in Canada, and if you want one for your own home gym, it'll run you about $3,000. Would you be into using a Brain Bike if it showed up at your gym?

Source

Trying to Lose Weight? Ask These Questions

FitSugar — Mon, 16 Nov 2009 12:00:26 -0800

Many of the people reading FitSugar have weight loss on the brain, but are your efforts really necessary? Are those extra pounds putting your health at risk, or are you just carrying around a little harmless fluff? WebMD outlined seven questions you should ask yourself to help decide if you really need to get serious about weight loss.

What is your lifestyle? "Regular physical activity and healthy eating are important," say experts who spoke with WebMD, not just for those trying to budge the scale. If you're not active and eat poorly, you should start making some changes for your overall health, not just because of a weight-loss goal.
What is your family history? If high cholesterol, "high blood pressure, heart disease, diabetes, or another weight-related ailment" runs in your family then Web MD notes that "it's crucial to be mindful of your weight."
What is your weight history? If the pounds have been creeping up on you over the past several years, you need to watch out since "experts say your BMI should not increase dramatically, even as you age. Even moderate weight gain in adulthood can increase your risk of diabetes."

To see the other four questions read more.

How is your weight distributed? WebMD warns that if your body is "the so-called 'apple' shape," it can put your health at risk. So if this sounds like you, aim to whittle away your middle. If your weight is primarily in your thighs and butt, it's not as crucial to drop the pounds.
What is your waist size? The National Institutes of Health say that a "waist circumference of over 35 inches in women signifies a health risk, particularly those people with BMIs of 25 and 34.9 (the overweight category)." If you're not sure what your BMI is, check out Fit's Calculator to find out.
What is your health profile? "If your cholesterol and blood pressure levels are high and your BMI falls into the overweight or obese category, it's important to lose weight," writes WebMD. So make an appointment with your doc to get yours checked.
How do you feel? "If you're overweight and have joint problems, shortness of breath, or other health troubles that limit your day-to-day living," and interfere with being able to work, then experts quoted in the article suggest that melting away pounds would help improve the quality of your life.

Why Exercise Won't Help You Lose Weight . . . Sort Of

FitSugar — Thu, 05 Nov 2009 03:00:36 -0800

There have been a lot of reports in the last year confirming that contrary to popular belief, not all exercise leads to significant weight loss. If you want to shed pounds, it mostly comes down to diet. It’s no surprise that changing your diet can help you lose weight, but for decades, many people believed that exercise was the best pathway to a slimmer, fitter you.

Today the New York Times added to the news that exercise doesn’t significantly aid in weight loss by reporting the results of an exercise and obesity study. The study followed a group of 58 obese individual who underwent three months of supervised aerobic activity but didn’t change their diets at all. And while the group lost an average of seven pounds, many participants barely lost three.

I admit that when all of these studies started coming up I was a little shocked, but it turns out that high intensity workouts mainly burn carbs, not just fat.

To hear what type of exercise may maximize fat loss, read more.

The article explains: "'The message of our work is really simple,' although not agreeable to hear, said Edward Melanson, PhD, the lead author of the study. 'It all comes down to energy balance,' or, as you might have guessed, calories in and calories out. People 'are only burning 200 or 300 calories' in a typical 30-minute exercise session, Melanson points out. 'You replace that with one bottle of Gatorade.'"

Fat loss can be maximized, but it’s a matter of how you approach your workout. To do this, work out at a lower intensity in your fat-burning zone, which is 60 to 70 percent of your maximum heart rate. For most people this zone falls between 105-134 beats per minute. Melanson’s study also found that once weight is lost from reduced calorie intake, exercise might prevent it from coming back by resetting metabolic pathways that stop the body from wanting to store fat.

The research is interesting, but should not dissuade any of us from our fitness goals. The benefits of exercise reach far beyond weight loss - it helps the brain function better, reduces stress, creates a toned body, and is important for healthy heart function.

Surfing the Web Slows Down Dementia

FitSugar — Mon, 26 Oct 2009 15:00:22 -0700

Spending an hour or two a day online might not be so bad after all. A new study suggests that spending time on the Internet increases brain activity in areas of the brain related to memory and cognition.

The study followed 24 volunteers between the ages of 55 to 78. Half of the participants were familiar with the Internet, while the other half had little to no Web experience.The study showed that amongst the participants, surfing the web stimulated the brain more than reading a book. Results also showed that the positive effects extended long after the web activity ended. Brain activation patterns of patients that had little knowledge of the Internet was that over time their grew with their experience.

Researchers speculate that not any old surfing will do.The lesson here is that it's important to keep the mind engaged and challenged whether it's surfing the Internet, doing crossword puzzles, or even playing video games.

Physical Traits Give Clues About Your Health Risks

FitSugar — Tue, 06 Oct 2009 08:00:15 -0700

There are many things we can do to enhance our health and prevent illness. Exercising regularly, eating a healthy diet, not smoking, limiting your alcohol intake, and reducing your stress can add years to your life. Who knew that your appearance and physical characteristics such as finger length and your sense of smell could let you know what health risks you might be prone to? Check out the list below from Prevention magazine.

Finger length: For women, if your index finger is shorter than your ring finger, then it means you have double the risk of osteoarthritis of the knee. If yours is longer or even with your ring finger, you're in the clear, but if it's not, do exercises to strengthen your knees, such as squats and lunges. Arthritis and finger length are both related to low levels of estrogen, so that's why the two are connected.
Arm length: Extend your arms in T-position out to the sides and measure the distance form fingertip to fingertip. If the distance is less than 60 inches, you're at a higher risk for Alzheimer's. So do activities that stimulate your brain and your body. Take a painting class, learn to play a musical instrument, play chess, or take dance lessons.

There's more, so keep reading

Brain tumors - primary

FitSugar — Wed, 08 Oct 2008 17:35:12 -0700

In This Report

Highlights
Introduction
Symptoms
Risk Factors
Causes
Prognosis
Diagnosis
Common Brain Tumors
Treatment
Surgery
Radiotherapy
Chemotherapy
Other Treatments
Treatment of Complications...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Radiation Therapy Complications

Radiation therapy in children with cancer increases the risk of new brain and spinal cord tumors, suggests a study in the Journal of the National Cancer Institute. The risk appears to increase along with the radiation dosage. Children who receive radiotherapy before age 5 are especially at risk for second primary tumors.
Survivors of childhood brain tumors who received cranial radiotherapy as part of their treatment are at risk for later having a stroke, indicates a study in the Journal of Clinical Oncology. The average length of time from brain tumor diagnosis to post-treatment stroke was 14 years.

Radiation Therapy for Elderly Patients

Radiotherapy provides modest improvement in survival for elderly patients (age 70 years and older) with glioblastoma, with no detriment to quality of life or cognition function, according to a 2007 study in the Journal of the American Medical Association.

Temozolomide (Temodar)

The chemotherapy drug temozolomide (Temodar) has become an important and effective treatment for patients newly diagnosed with glioblastoma. However, not all patients respond equally well to this drug. A 2007 study in the journal Neurology suggests that a patient’s genotype may explain differences in response. Though genetic testing, researchers found that temozolomide works best in people who are missing a particular gene.

Investigational Treatments

Vorinostat (Zolinza), a cancer drug used for T-cell lymphoma, may help patients with recurrent glioblastoma multiforme, according to research presented at the 2007 annual meeting of the American Society of Clinical Oncology.
Bevacizumab (Avastin), a targeted therapy drug used for lung and colorectal cancers, may help prolong survival in patients with advanced glioma, indicates a 2007 study in Clinical Cancer Research. Another anti-angiogenesis drug, cediranib (Recentin), may help make glioblastomas more responsive to chemotherapy and radiotherapy, according to recent interim trial results.
Vitespen (Oncophage), an experimental vaccine for glioma, is showing promise in early clinical trials, suggests research presented at the 2007 meeting of the American Association of Neurological Surgeons.

Introduction

Brain tumors are composed of cells that exhibit unrestrained growth in the brain.

The major areas of the brain have one or more specific functions.

They can be benign (noncancerous, meaning that they do not spread elsewhere or invade surrounding tissue) or malignant (cancerous).

Cancerous brain tumors are further classified as either primary or secondary tumors. Primary tumors start in the brain, whereas secondary tumors spread to the brain from another site such as the breast or lung. (In this report, the term "brain tumor" will refer mainly to primary malignant tumors, unless otherwise specified.)

Benign tumors represent half of all primary brain tumors. Their cells look relatively normal, grow slowly, and do not spread (metastasize) to other sites in the body. Benign tumors can still be serious and even life-threatening if they are in vital areas in the brain where they exert pressure on sensitive nerve tissue or if they increase pressure within the brain. While some benign brain tumors may pose a health risk, including risk of disability and death, most are usually successfully treated with techniques such as surgery.

Click the icon to see an image of a primary brain tumor.

A secondary (metastatic) brain tumor occurs when cancer cells spread to the brain from a primary cancer in another part of the body. Secondary tumors are about three times more common than primary tumors of the brain. Usually, multiple tumors develop. Solitary metastasized brain cancers may occur but are less common. Most often, cancers that spread to the brain to cause secondary brain tumors originate in the lung, breast, kidney, or from melanomas in the skin.

A primary malignant brain tumor is one that originates in the brain itself. Although primary brain tumors often shed cancerous cells to other sites in the central nervous system (the brain or spine), they rarely spread to other parts of the body.

Brain tumors are generally named and classified according to the following:

The normal brain cells from which they originate, or
The location in which the cancer develops

The biologic diversity of these tumors, however, makes classification difficult, and some experts believe that more specific categories are needed.

About half of all primary brain tumors are known collectively as gliomas. They are cancerous forms of glial cells, the building-block cells of the connective, or supportive, tissue in the central nervous system. There are several glial cells types from which gliomas form. Their names are:

Astrocytomas are primary brain tumors derived from astrocytes, which are star-shaped glial cells. Normal astrocytes provide nutrients, support, and insulation for nerve cells and are one of the primary neurologic cells in the body. The malignant astrocytomas called glioblastomas account for 23% of brain tumors and are the most common ones.
Oligodendrogliomas develop from oligodendrocyte glial cells, which form the protective coatings around nerve cells. Although oligodendrogliomas were thought to represent about 5% of all gliomas, more recent evidence suggests they may comprise about 20% of gliomas. Pure oligodendrogliomas, however, are rare. In most cases they occur in mixed gliomas.
Ependymomas are derived from ependymal cells, which line the ventricles (fluid-filled cavities) in the lower part of the brain and the central canal of the spinal cord. They constitute about 6% of all primary tumors in the central nervous system. About 30% of these tumors occur in the spinal cord.
Mixed gliomas contain a mixture of malignant gliomas. About half of these tumors contain cancerous oligodendrocytes and astrocytes.

It should be noted that gliomas may also contain cancer cells derived from brain cells other than glial cells.

Some brain tumors are categorized by their location in the brain. Such tumors often contain gliomas but are also frequently a mixture of different cell types.

Meningiomas. Meningiomas are usually benign tumors that develop in the membranes that cover the brain and spinal cord (the meninges).

Click the icon to see an image of the meninges.

They are not technically classified as brain tumors, but they have similar symptoms and develop within the brain. So in practical terms, they are considered brain tumors. In fact, meningiomas comprise 20% of all primary brain tumors. They occur more often in women than in men. Most grow very slowly, and the majority of people who have them never know they are present. Malignant forms called anaplastic meningiomas and hemangiopericytomas are less common and are difficult to remove surgically.

Cerebral Astrocytomas. Gliomas that develop inside the brain often occur in the cerebral hemispheres (the right and left sides of the brain). In such cases, they are referred to as cerebral astrocytomas. Gliomas sometimes occur in another part of the brain, called the cerebellum. The cerebellum is responsible for balance and coordination. In such cases, the term cerebellar astrocytoma is used.

Click the icon to see an image of the function of the left cerebral hemisphere.

Click the icon to see an image of the function of the right cerebral hemisphere.

Brain Stem Gliomas. Brain stem gliomas develop in the lowest portion of the brain. The brain stem connects the cerebrum (the higher centers of the brain) to the spinal cord. The brain stem is thought to be the primitive brain because it controls the most basic functions.

Click the icon to see an image of the function of the brainstem.

The brain stem consists of three primary parts:

The medulla regulates breathing, swallowing, blood pressure, and heart rate.
The pons links the cerebellum to the cerebrum.
The midbrain helps control vision and hearing.

Click the icon to see an image of the structures of the brain.

Medulloblastomas. Medulloblastomas are always located in the cerebellum, which is at the base and toward the back of the brain. They represent about 3% of all brain tumors.

Click the icon to see an image of the function of the cerebellum.

Pituitary Tumors. Pituitary tumors comprise about 10% of primary brain tumors and are often benign, slow-growing masses in the pituitary gland.

Click the icon to see an image of the pituitary gland.

Other Brain Tumor Locations. Optic nerve gliomas occur in the optic nerve, which is located behind the eye. Acoustic neuromas make up 7.5% of brain tumors.

Click the icon to see an image of the optic nerve.

Symptoms

Brain tumors produce a variety of symptoms, ranging from headache to stroke. They are great mimics of other neurologic disorders. Symptoms occur if the tumor directly damages the nerves in the brain or central nervous system or if its growth imposes pressure on the brain. Some gliomas develop gradually, and symptoms may be subtle for a long time, making an early diagnosis difficult.

Headache is probably the most common symptom of a brain tumor. It should be strongly emphasized, however, that everyone has headaches, and they rarely represent an underlying brain tumor. Headaches caused by brain tumors may vary depending on the location, and many different features.

Steady and worse upon waking in the morning and clears up within a few hours
Persistent non-migraine headache that occurs while sleeping and is also accompanied by at least one other symptom (such as vomiting or confusion)
May or may not be throbbing, depending on location of the tumor
Accompanied by double vision, weakness, or numbness
May worsen with coughing or exercise or with a change in body position
Sometimes accompanied by neck pain

Gastrointestinal symptoms, including nausea, are also common. Nausea and vomiting, in fact, often occur in children with brain tumors and in all people with brain stem cell tumors.

Seizures occur in between 15 - 95% of patients, depending on the location of the tumor.

Tumors are more likely to be localized and affect one area of the brain. In such cases they can cause partial seizures. In this case, a person does not lose consciousness but may experience confusion, jerking movements, tingling, or odd mental and emotional events.
Generalized seizures, which can cause loss of consciousness, are less common, since they are caused by disturbances of nerve cells in diffuse areas of the brain.

Sometimes the only symptoms are mental changes, which may include the following:

Memory loss
Impaired concentration
Problems with speech and reasoning
Increased sleep

Gradual loss of movement or sensation in an arm or leg
Unsteadiness
Unexpected visual disturbance (especially if it is associated with headache), including vision loss (usually of peripheral vision) in one or both eyes or double vision
Hearing loss with or without dizziness
Speech difficulty

Specific symptom syndromes may help identify the tumor. The following are some examples.

Symptoms of Brain Stem Gliomas. Sudden onset of symptoms that include vomiting (usually just after waking), a clumsy walk, muscle weakness on one side of the face, difficulty in swallowing, slurred or nasal speech, as well as impaired hearing or vision.

Symptoms of Glioblastoma Multiforme. Rapid onset and worsening of symptoms that include headaches, seizures, memory loss, and changes in behavior.

The below symptoms indicate an emergency condition and require immediate medical attention:

Pupil dilation
A fixed gaze
Paralysis on one or both sides of the body
Blindness or defective vision in one eye

Risk Factors

Nearly 360,000 people in the U.S. are living with brain cancer. Men are at higher risk than women for most brain tumors. Primary malignant brain tumors are still uncommon and represent only 1.3% of all cancers diagnosed in the United States and 2.4% of all deaths due to cancer.

Primary brain cancers are rare, occurring in slightly more than 11 people per 100,000 per year. There has been some evidence of a growing incidence of brain cancer among the elderly since the 1980s. The increase, however, is most likely due to the rise in incidence of non-Hodgkin's lymphomas -- which can occur in the brain. When this malignancy is eliminated, any increase in other tumors is not significant.

The average age of diagnosis for brain tumors is 57, and about 90% of primary brain tumors occur in adults. These tumors can develop at all ages, usually peaking in two age groups.

In adults, ages 55 - 65
In children, ages 3 - 12

Risk Factors in Children. Tumors in the central nervous system are now the most common primary cancers in children, but they are still rare. An estimated 3,110 benign or malignant brain tumors are expected to be diagnosed in children each year. Brain tumors in children are more likely to occur in the cerebellum, the midbrain, or the optic nerve.

The incidence has increased over the past years, but there is some evidence that this increase is only due to better diagnostic procedures. The mortality rate has actually decreased. Researchers have attempted to uncover risk factors for childhood brain cancer. There may be some association between a higher risk and the following conditions:

Children treated with radiation to the head for leukemia and who have a specific genetic defect may face a high risk for brain cancer. (It should be noted that for children without this defect, the risk is very small.)
Having parents with specific cancers. (According to one study, having parents with nervous system cancers, colon cancer, or cancer in the salivary glands increased the risk of specific brain tumors in their children.)

Click the icon to see an illustrated series detailing colon cancer surgery.

The risk for primary brain tumors in Caucasians is higher -- as much as twofold depending on type -- than in African-Americans.

Radiation Exposure. People who receive radiation therapy to the head during cancer treatment have an increased risk of developing brain tumors 10 - 15 years later. Workers in the nuclear industry are also at increased risk.

There is no evidence that electromagnetic field exposure from power lines or household appliances poses any risk. Several recent epidemiological studies, including a 2006 study in the British Medical Journal, found that cell phones, cordless phones, and wireless devices are also safe and do not increase the risk for gliomas.

Chemical and Metals in Brain Tumors. High exposure to numerous metals and chemicals have been associated with brain tumors:

Industrial chemicals, including vinyl chloride and petroleum products
Lead, arsenic, or mercury exposure
Exposure to pesticides. A major study of pesticides is underway, but results are not in yet. A 2003 study indicated that parental exposure to pesticides or herbicides did not appear to be important in increasing risk for brain cancer in their children.

Brain cancer is uncommon, and, over the course of their lifetime, many people are exposed to these chemicals, many of which are very common. To date, there has been no clear evidence that implicates any specific industrial chemical or metal.

One study reported a higher risk for brain cancers in patients who had undergone organ transplantations. Researchers believed that the drugs used to suppress the immune response after the procedures may increase the risk.

One study reported lower risks for brain cancers in individuals with allergies and autoimmune diseases (such as type 1 diabetes). Autoimmune diseases were also associated with a lower risk for meningiomas. The cause of this possible association remains unknown.

Studies have also found an association between lower risk for gliomas and a history of infection with varicella zoster, the virus that causes chicken pox and shingles.

Click the icon to see an image of the chicken pox.

Causes

Only 5 - 10% of primary brain tumors are associated with genetic disorders. These inherited conditions and associated genes include:

Von Recklinghausen disease, also called neurofibromatosis 1 (NF1 gene) and neurofibromatosis 2 (NF2 gene)
Turcot's syndrome (APC gene)
Gorlin syndrome, also called basal cell naevus syndrome (PTCH gene)
Tuberous sclerosis (TSC1 and TSC2 genes)
Li-Fraumeni syndrome (TP53 gene)

Certain types of brain tumors are specifically linked with these genetic conditions. For example, neurofibromatosis 1 is associated with about 15% of cases of pilocytic astrocytomas, the most common type of childhood glioma. Neurofibromatosis results from defects in the tumor suppressor genes NF1 and NF2. Li-Fraumeni syndrome results from mutations in the tumor suppressor gene TP53. These mutations affect the production of tumor suppressor protein p53.

Tumor suppressor genes regulate cell division and help repair DNA damage. When mutations that affect protein encoding occur, unregulated cell division and growth can lead to the development of a tumor. Tumor suppressor genes are sometimes described as being in a tug-of-war with cancer-causing genes called oncogenes. Oncogenes derive from mutations or overexpressions of proto-oncogenes. Proto-oncogenes encode for proteins that regulate cell growth and differentiation. When proto-oncogenes become oncogenes, normal cells start to grow uncontrollably. Cancer can occur when tumor suppressor genes are turned off, or when oncogenes are turned on.

Many different oncogenes are involved in cancer. Growth factors are a particularly important type of oncogene associated with brain tumors. Growth factors attach to receptors (connectors) that stimulate cell growth. Epidermal growth factor receptor (EGFR) has been shown to play a role in high-grade brain tumors such as glioblastoma multiforme. In 2007, scientists identified insulin-like growth factor binding protein (IGFBP2) with an oncogene that may be associated with the development of astrocytoma and oligodendroglioma.

Knowing the molecular origin of a brain tumor may help determine the treatment course, both for standard chemotherapy and "targeted therapy" biologic drugs. For example, patients with tumors marked by high EGFR proliferation may benefit from treatment with the EGFR kinase inhibitor drugs gefitinib (Iressa) or erlotinib (Tarceva).

Most genetic abnormalities that cause brain tumors are not inherited but occur as a result of environmental or other factors that affect genetic materials (DNA) in the cells. Researchers are studying various environmental factors (viruses, hormones, chemicals, radiation) that may trigger the genetic disruptions that lead to brain tumors in susceptible individuals. They are also working to identify the specific genes that are affected by these environmental triggers. For example, in a 2007 study, scientists proposed that genetic susceptibility may explain why some people develop meningioma, a rare type of brain tumor, following exposure to ionizing radiation. Future investigations will hopefully identify the specific genes involved and help determine which people would potentially be most at risk.

Prognosis

About 13,100 people die from cancerous brain tumors each year. Recent advances in surgical and radiation treatments have significantly extended average survival times and can reduce the size and progression of malignant gliomas. In general, survival rates are highest in younger people and lowest in the elderly.


Age	Survival Rates
0 - 19 years	63.1%
20 - 44 years	50.4%
45 - 64 years	14.2%
Over 65	4.9%
Data From: 2002 - 2003 Primary Brain Tumors in the United States Statistical Report. Fact Sheet (1973- 1999 data). Brain Tumor Registry of the United States www.cbtrus.org/factsheet/factsheet.html.

In general, studies are reporting that patients who survive the first 2 years after a diagnosis of a brain tumor have at least a 70% chance of surviving for at least 5 years. The best recent progress has been made for:

Medulloblastomas in both children and adults. Long-term survival rates are now about 60% in children after treatment for medulloblastomas, the most common malignant brain tumor in this age group. (New treatments, however, may significantly improve these rates.)
Nonmalignant astrocytomas and oligodendrogliomas in adults.

Unfortunately, the majority of primary brain tumors, notably anaplastic astrocytomas and glioblastoma multiforme, are only rarely curable.

The specific effects of tumors on the brain can cause seizures, mental changes, and mood, personality, and emotional changes. Such effects can be devastating to the patient and the caregivers. Numerous treatments are available that help alleviate these complications, and patients and family members should discuss these with their doctors.

Diagnosis

A neurological exam is usually the first test given when a patient complains of symptoms that suggest a brain tumor. The exam includes checking eye movements, hearing, sensation, muscle movement, sense of smell, and balance and coordination. The doctor will also test mental state and memory.

X-rays of the skull were once standard diagnostic tools but are now performed only when more advanced procedures are not available. Advanced imaging techniques have dramatically improved the diagnosis of brain tumors in recent years.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) is the gold standard for diagnosing a brain tumor. It does not use radiation and provides pictures from various angles that can enable doctors to construct a three-dimensional image of the tumor. It gives a clear picture of tumors near bones, smaller tumors, brainstem tumors, and low-grade tumors. MRI is also useful during surgery to show tumor bulk, for accurately mapping the brain and for detecting response to therapy.

An MRI (magnetic resonance imaging) of the brain creates a detailed image of the complex structures in the brain. An MRI creates a three-dimensional picture of the brain, which allows doctors to more precisely locate problems such as tumors or aneurysms.

A variant called magnetic resonance spectroscopy (MRS) is capable of providing information on the activity of the brain using magnetic resonance imaging. MRS is proving to be accurate for distinguishing dead (necrotic) tissue caused by previous radiation treatments from recurring tumor cells in the brain, a difficult diagnostic issue.

Computed Tomography. Computed tomography (CT) uses a sophisticated x-ray machine and a computer to create a detailed picture of the body's tissues and structures. It is not as accurate as an MRI and does not detect about half of low-grade gliomas. It is useful in certain situations, however. Often, doctors will inject the patient with an iodine dye, called contrast material, to make it easier to see abnormal tissues. A CT scan helps locate the tumor and can sometimes help determine its type. It can also help detect swelling, bleeding, and associated conditions. In addition, computed tomography is used to check the effectiveness of treatments and watch for tumor recurrence.

Click the icon to see an image of a CT scan of the brain.

Positron Emission Tomography. Positron emission tomography (PET) provides a picture of the brain's activity rather than its structure by tracking substances that have been labeled with a radioactive tracer. As with magnetic resonance spectroscopy (MRS), it is also able to distinguish between recurrent tumor cells from dead cells or scar tissue, although MRS is more widely available. PET is not routinely used for diagnosis, but it may supplement MRIs to help determine tumor grade after a diagnosis. Data from PET may also help improve the accuracy of newer radiosurgery techniques.

Other Imaging Techniques. Numerous other advanced imaging techniques may be used for specific purposes, if available or under investigation.

Single photon emission tomography (SPECT) is similar to PET but is not as effective in distinguishing tumor cells from destroyed tissue after treatments.
Magnetoencephalography (MEG) scans measure the magnetic fields created by nerve cells as they produce electrical currents.
Cerebral angiography involves x-rays of blood vessels in the brain. A long, thin tube (catheter) is threaded through blood vessels from a distant site to the brain, and a radiopaque substance (a substance that is impenetrable to x-rays) is injected through it. The role of angiography in glioma is usually limited to planning surgical removal of a tumor suspected of having a large blood supply.
Radionuclide brain scintigraphy uses a radioactive substance that is administered and absorbed by capillaries in the tumor, which are then viewed using imaging techniques.
Digital holography, a new technique that provides full three-dimensional mapping, is under investigation.

A lumbar puncture is used to obtain a sample of spinal fluid, which is examined for the presence of tumor cells. A computed tomography (CT) scan or magnetic resonance imaging (MRI) should generally be performed before a lumbar procedure to be sure that the procedure will be safe.

Click the icon to see an image of a lumbar puncture.

A biopsy is a surgical procedure in which a small sample of tissue is taken from the suspected tumor and examined under a microscope for malignancy. The results of the biopsy also provide information on the cancer cell type.

In some cases, such as brain stem gliomas, a biopsy might be too hazardous because removing any healthy tissue from this area can affect vital functions. In such cases, diagnosis must rely on less invasive and possibly less accurate measures. Of promise is the stereotactic technique (also called stereotaxy), which uses computers to provide three-dimensional views of very small areas. This may allow precise biopsies of cancer cells without affecting healthy brain tissue. Expertise in this technique is extremely important, however, and the technique is not widely available.

The survival rates in people with brain tumors depend on many different variables:

Whether the tumor is malignant or benign
Cancer cell type and location (location affects whether the tumor can be removed surgically or not)
The tendency to spread and the growth rate (tumor grade)
Patient's age
Patient's ability to function
Duration of symptoms

The outlook is poorer in the very youngest and very oldest patients, although younger patients who survive 2 years after diagnosis have a much better outlook than older patients.

Grading Tumors. Malignant primary brain tumors are classified according to tumor grade. Grade I is the least cancerous, and Grades IV and V are the most dangerous. Grading a tumor attempts to predict its tendency to spread and its growth rate. It is based on the appearance of the tumor cells as seen under a microscope.

Lower-grade (I and II) tumor cells are well defined and almost normal-shaped. (Some primary low-grade brain tumors are curable by surgery alone, and some are curable by surgery and radiotherapy. Low-grade tumors tend to have the most favorable survival rates and high-grade the least. However, this is not always the case. For example, some low-grade II gliomas are at very high risk for progression.)
Higher-grade (III and IV) tumor cells are abnormally shaped and are more diffuse, which indicates more aggressive behavior. (High-grade brain tumors usually require surgery, radiotherapy, chemotherapy, and possibly investigational treatments.)
In tumors that contain a mixture of different-grade cells, the tumor is graded using the highest-grade cells in the mixture, even when there are very few of them.

Biologic Markers. Elevated levels of certain cancer-associated molecules or compounds may be correlated with prognosis. For example, evidence of genetically mutated p53 indicates a poorer prognosis in younger patients with glioblastoma multiforme.

Elevations of epidermal growth factors (EGF) or vascular endothelial growth factors (VEGF) suggest aggressive tumors. High levels of the receptor for EGF (EGFR), in fact, are found in 70% of glioblastoma specimens.

Genetic Profiles of Cancer Cells. Analyses that identify genetic types may soon help clinicians determine if patients with specific brain tumor cells might respond better to one treatment than another. For example, specific genetic profiles of oligodendrogliomas can help predict how patients respond to nitrosourea alkylating drugs such as carmustine. Genetic variation tests are also being used to determine how patients may respond to epidermal growth factor receptor (EGFR) kinase inhibitors, such as erlotinib (Tarceva) and gefitinib (Iressa).

A genetic profile can also help give doctors a better idea of a patient’s prognosis and survival. In a 2006 study of patients with anaplastic oligodendroglioma, the status of specific chromosomal deletions within tumors was a better predictor of survival than which kind of treatment patients received. In fact, the researchers suggested that gliomas be classified according to chromosomal deletion status, and recommended that chromosomal testing be a regular part of diagnosis and treatment decisions.

Common Brain Tumors


GENERAL DESCRIPTION OF ASTROCYTOMAS: Derived from star-shaped glial cells called astrocytes.

Low-Grade (Usually I) Astrocytomas. Pilocytic gliomas.	Pilocytic gliomas occur mostly in children. Tumors are well differentiated. Cells are relatively normal and rarely metastasize. They grow relatively slowly. Pilocytic astrocytomas have the highest 5-year survival rates (greater than 70%). However, even well differentiated astrocytomas are life threatening if they are inaccessible.	Cancer may sometimes be completely removed through surgery, particularly if it occurs in the cerebellum. For recurrence or residual tumors, reoperation, radiotherapy, or chemotherapy may be given, depending on the circumstances. Repeat surgery for cerebellar astrocytoma is often very successful. For those who fail radiotherapy and chemotherapy, investigative drugs are used.
Low-Grade (II) Astrocytomas. Fibrillary, protoplasmic, and protoplasmic astrocytomas. Some pleomorphic xanthoastrocytomas.	Tumors are well differentiated. Cells are relatively normal and less malignant than those in higher grades. They grow relatively slowly but can spread. Survival rates average 5 years, but people can survive for a decade or more. Pleomorphic xanthoastrocytomas have a relatively favorable prognosis, but can recur and demonstrate aggressive clinical behavior. Low-grade astrocytomas generally occur in young adulthood, with a peak incidence in 30s and 40s.	Surgery, if possible, plus radiotherapy. Surgery alone in certain children, if possible. Trials on postoperative radiotherapy include the following: radiotherapy with or without chemotherapy; low-versus-high radiotherapy doses (studies suggest results are the same and high-dose causes more side effects); deferring radiotherapy until tumor progresses and symptoms occur. (A major study confirmed earlier ones that suggest that this approach has the same 5-year survival benefits -- about 65% -- as immediate postoperative radiotherapy.)
Malignant (High-grade III and IV) Astrocytomas. Anaplastic astrocytoma (gemistocytic and some pleomorphic xanthoastrocytomas). Usually mid-grade (III).	Tumors grow more rapidly than lower grades and infiltrate other nearby healthy cells. Not well-differentiated. Five-year survival rates are about 30%. Recurrence is common.	Treatment same for all high-grade malignant astrocytomas. Surgery, with removal of as much of tumor as possible followed by radiotherapy, with or without chemotherapy. The addition of chemotherapy, particularly being able to take more than 6 cycles, appears to improve survival rates. Carmustine (BCNU) most effective drug at this time. Other drugs and treatment sequences are under investigation. For example, temozolomide is showing promise for many patients, including the elderly. Topotecan may also be useful with other drugs or with radiation. For recurring gliomas, surgery with placement of wafers that release carmustine (Gliadel wafers) is the only proven beneficial therapy to date. Combinations, such as procarbazine and carmustine, provide benefits for recurrent anaplastic astrocytomas. Single drugs may be less toxic and as helpful for other recurrent gliomas. Temozolomide has been approved in Europe for high-grade recurrent gliomas and is proving to be beneficial. Other trials include the following: drugs that block small molecules involved in tumor growth; radioimmunotherapy using monoclonal antibodies; advanced radiotherapy techniques; intraarterial chemotherapy.
High-grade (IV and V). Glioblastoma (notably glioblastoma multiforme or GBM).	Very rapidly growing tumors that spread quickly. Represents about 25% of all primary brain tumors. Most common in older adults (over age 55) and affect more men than women. Recurrences are common in patients who achieve long-term survival.


GENERAL DESCRIPTION OF EPENDYMOMAS: Derived from cells that line the ventricles (fluid-filled brain cavities) and spinal cord central canal. Do not usually spread into normal brain tissue. Can block exits for cerebrospinal fluid and cause hydrocephalus. They constitute about 4% of all central nervous system tumors in adults and 10% of these tumors in children. About 30% of ependymomas develop in the spinal column.

Low-grade (I). Myxopapillary ependymoma (found in the spine). Subependymoma (found in one of the ventricles).	No or very slow growth. In addition to grade, risk is also based on location of the tumor. Tumors on the spinal cord are more accessible than those in the fourth ventricle or in the middle of the lower back portion of the brain.	Can often be removed and cured with surgery, particularly those on spinal cord. Radiation may be needed. Chemotherapy (avoid radiation, if possible) in children under age 6).
Low-grade (II). Papillary, cellular, and clear cell ependymomas.	Slow growth. Usually affect adults.	Surgery alone or followed by radiotherapy. For those who fail radiotherapy, possible use of nitrosourea-based chemotherapies or investigative drugs.
Grade III. Anaplastic ependymomas.	Spreads to the spinal fluid.	Surgery followed by radiotherapy to brain and spinal cord. Possible shunt.
Grade IV. Primitive neuroecto-dermal tumor (PNET). Composed of malignant forms of early, undeveloped nerve cells called neuroblasts. (This malignancy is also referred to as neuroblastoma.)	Very rare, but more common in children. Primitive nerve cells that grow very rapidly. Usually occur in cerebellum.	Surgery followed by radiotherapy to brain and spinal cord. Chemotherapy in young children. Investigative high-dose chemotherapy with stem cell rescue for children with relapsed cancer.


DESCRIPTION OF OLIGODENDROGLIOMAS: They develop from oligodendrocyte glial cells. These cells form the protective coatings around nerve cells. Pure cell types are rare. Most often occur in mixed gliomas. Categorized as either low- or high-grade. Most are low-grade II.

Low-grade: Low grade difficult to tell from astrocytomas, although they are usually calcified. Very likely to bleed. Usually spread along nerve pathways of the brain and spine and rarely outside this area. In spite of difficulty in removing surgically, in some patients survival can be 30 - 40 years. Usually have better prognosis than astrocytomas of equal grade. Occur mostly in middle-aged adults, although there is also a small peak of incidence in children.	Treatment usually delayed until progression causes symptoms. Surgery to remove whole tumor. Radiotherapy often follows in all adults over age 40 or in anyone in which tumor cannot be completely removed. Solid evidence is lacking on this approach, however, and there is some debate on its benefits. Trials using chemotherapy after radiation are promising. Two-thirds of patients respond to PCV (combination of procarbazine, lomustine and vincristine.) Sustained remissions averaging 16 years often achieved. Pure oligodendrogliomas respond better than mixed gliomas. Temozolomide is showing promise as second-line treatment. Others under investigation. Trials of additional chemotherapy for less well-differentiated tumors or for residual tumors after surgery.
High-grade. Anaplastic oligodendrogliomas.	Immediate treatment. Surgery to remove the whole tumor, if possible. Radiation typically follows surgery. Chemotherapy treatments either before or with radiation. Standard drugs are limited. Experts recommend trying investigative drugs. Temozolomide and retinoic acid may be useful. Possible additional drugs include melphalan, thiotepa, carboplatin, cisplatin, and etoposide. (Numerous biologic markers may help identify specific oligodendrogliomas that will respond better or worse to specific treatments.)


GENERAL DESCRIPTION OF MIXED GLIOMAS: Mixed gliomas contain a mixture of malignant gliomas. About half of these tumors contain cancerous oligodendrocytes and astrocytes.

Grade determined by the highest-grade cell present in the tumor.	Same as for oligodendroglioma.



Meningiomas	They are found in the membranes around the brain and spinal column. They are usually benign and rarely invasive. In such cases, long-term outlook is very favorable. (Malignant forms, anaplastic meningiomas, and hemangiopericytomas are uncommon and occur in about 2% of cases.)	Usually watchful waiting. Aggressive surgery the treatment of choice, if possible, although 20% recur after 10 years. Malignant forms and those at the base of the skull difficult to impossible to remove surgically. Stereotactic radiosurgery or fractionated external beam radiotherapy showing promising results for some patients.
Cerebellar astrocytomas (located in cerebellum)	Located in the cerebellum. Usually low-grade, but depends on cell type. If surgical removal is complete, up to 90% survival rates. More common in children than adults.	Surgery primary treatment. Radiotherapy if removal is incomplete.
Brain Stem Gliomas	About 60 - 70% of brain stem tumors are diffuse, which are likely to spread and have a rapid onset of symptoms. Focal tumors tend to be solid or cyst-like. They generally develop gradually. Occurs in both children and young adults.	Radiation is usual treatment. Tumors in this area are rarely removed surgically since the nerve tissue in this area is responsible for vital life functions. Slow-growing tumors may only require watchful waiting. Trials using advanced radiotherapy techniques, gene therapy, immunotherapy, and other experimental drugs.
Medulloblastomas	Occurs in cerebellum (the lower portion of the brain), brainstem, and spinal cord. Usually fast-growing aggressive cells. Most common brain tumors in children and young people, causing between 15 - 20% of brain tumors. With aggressive therapy, in children 5-year survival rates between 60 - 80%. In patients who survive for 2 years after diagnosis, long-term survival rate is nearly 80%.	Treatment is usually surgery and radiotherapy followed by chemotherapy. A 2005 study found that a combination chemotherapy regimen may replace radiation for very young children. A 2006 study suggested that radiation and chemotherapy doses should be adjusted based on disease severity.
Optic Tract Gliomas	Spread along the optic nerve. Usually slow growing. Most often in children under age 10. Children with these tumors often have vision and hormonal problems.	Usually surgery if one eye is involved. Possible chemotherapy or radiation.

Treatment

The approach for treating brain tumors is to reduce the tumor as much as possible using surgery, radiation treatment (also called radiotherapy), chemotherapy, or investigative procedures. Such treatments are used alone or, more commonly, in combinations. With some very slow-growing cancers, such as those that occur in the midbrain or optic nerve pathway, patients may be closely observed and not treated until the tumor shows signs of growth. The intensity, combination, and sequence of these treatments depends on the glioma subtype, its size and location, and patient age, health status, and medical history.

Recent advances in surgical and radiation treatments have significantly extended average survival times compared to those of standard therapy. Investigative treatments, such as monoclonal antibodies, are also showing promise. Patients or their caretakers should discuss all options thoroughly with a specialist in brain cancer. Different specialists may be needed to help manage symptoms.

Because of the low-cure rates of most malignant brain tumors, support for the patients and their families is a critical component of treatment and management. In response to one survey of patients with gliomas, experts made several recommendations to help both patients and caregivers:

Any physical impairment that could benefit from home equipment or physical therapy should be identified and treated.
Patients should discuss emotional as well as physical issues with their doctors. Depression, for instance, can be medically treated. Caregivers should also seek help for the inevitable stress, depression, and tension arising from their difficult role.
Relaxation techniques, meditation, and spiritual resources can be extremely helpful. Support groups are beneficial, but experts recommend separate groups for patients and their families.

Surgery

Surgery is usually the first step in treating most brain tumors. In some cases, however, such as most brain stem gliomas, it may be too dangerous to perform surgery. The object of most brain tumor surgeries is to remove or reduce as much of its bulk as possible. By reducing the size, other therapies, particularly radiotherapy, can be more effective. (Although there have been significant advances in brain surgeries, some experts argue that in high-grade gliomas extensive surgery may not improve survival rates at all and patients are best served by radiation therapy.)

The standard procedure is called craniotomy.

The neurosurgeon removes a piece of skull bone to expose the area of brain over the tumor.
The tumor is located and then removed.

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

There are various surgical options for breaking down and removing the tumor. They include:

Standard surgical procedures
Laser microsurgery (which produces great heat and vaporizes tumor cells)
Ultrasonic aspiration (which uses ultrasound to break the glioma tumor into small pieces, which are then suctioned out)

Relatively benign, grade I gliomas may be treated only by surgery. Some controversy exists over whether surgery for low-grade astrocytomas improves survival, although insufficient research has been conducted to prove its benefits for these gliomas. Most malignant tumors require additional treatments, including repeat surgery.

The surgeon's skill in removing the tumor as completely as possible is critical to survival. No one should be shy about asking the surgeon the number of similar procedures they have performed. (Asking for complication rates may not be useful, since a very experienced surgeon might operate on many high-risk patients.)

In most cancers outside the brain, surgical removal of a tumor usually involves taking out surrounding healthy tissue to be sure all cancer cells are gone. In the brain, however, removing healthy nearby nerve tissue can be as disastrous for the patient as the cancer itself. Special techniques have been developed to allow maximum removal of tumors while protecting healthy brain cells.

Stereotaxy. Stereotaxy has become a useful adjunct to both surgery (stereotactic surgery) and radiotherapy (stereotactic radiotherapy).

Cortical Localization. Cortical localization, or stimulation, uses a probe that passes a tiny electrical current to delicately stimulate a specific area of the brain. This produces a visible response of the body part (such as a twitch in a leg), which the stimulated region of the brain controls. The surgeon then knows to avoid those areas during the operation.

Image-Guided Surgery. Image guided surgery uses a three-dimensional picture of the patient's brain derived from computed tomography (CT) or magnetic resonance imaging (MRI) scans. An advanced technique called high-field interventional MR imaging (iMRI) is particularly accurate in identifying the tumor, but it is not widely available. The image, with various views of the brain, is displayed on a monitor in the operating room. During surgery, as the surgeon's instrument touches a part of the brain, a camera sends the image to a computer, which calculates the position of the surgical tool and displays it in its proper location on the 3-D image. The surgeon then can look at the monitor and see what structures to avoid.

Magnetic-Tipped Catheters. Neurosurgeons are investigating a technique in which external magnetic fields direct a magnet-tipped flexible catheter to the tumor site through a path that avoids harming certain important areas of the brain.

Heparin. Heparin, a blood-thinning drug, should be given at the time of surgery to help prevent blood clots.

Radiotherapy

Radiotherapy plays a central role in the treatment of most brain tumors, whether benign or malignant.

Radiotherapy after Surgery. Even when it appears that the entire tumor has been surgically removed, microscopic cancer cells often remain in the surrounding brain tissue. Radiation targets the residual tumor with the goal of reducing its size or stopping its progression. If the entire tumor cannot be removed safely, postoperative radiotherapy is often recommended. Even some benign gliomas may require radiation, since they may be life-threatening if their growth is not controlled.

Radiotherapy When Surgery Is not Appropriate. Radiotherapy may be used instead of surgery for inaccessible tumors or for tumors that have properties that are particularly responsive to radiotherapy.

Radiotherapy and Chemotherapy (Radiochemotherapy). Combining chemotherapy with radiotherapy is beneficial in some patients with high-grade tumors.

Various radiation treatments are now available.

Conventional radiotherapy uses external beams aimed directly at the tumor and is usually recommended for large or infiltrating tumors. It begins about a week after surgery and continues 5 days per week for 6 weeks. Older adults tend to have a more limited response to external-beam radiation therapy than younger people. According to a 2007 study in the New England Journal of Medicine, radiotherapy leads to a modest improvement in survival in elderly patients (70 years or older) with glioblastoma, and causes few negative impacts on quality of life or cognition.

For tumors that are highly localized, the radiation therapist has a choice of other radiation treatments:

Brachytherapy (also called interstitial radiation) uses radioactive "seeds" implanted directly in the tumor site. It is used as a booster to external beam radiation for patients with malignant astrocytoma. Brachytherapy appears to prolong survival in some aggressive gliomas. It may also be a safe and effective treatment for some children.
Intensity-modulated radiation therapy (IMRT) uses high-dose radiation beams that conform to the three-dimensional shape of the tumor.
Hyperfractionated radiation uses many small radiation doses to deliver a high total dosage of radiation.
A balloon catheter (GliaSite) that delivers radiation to the tumor cavity after surgery is showing promise.

Stereotactic radiosurgery has been developed to allow highly targeted radiation to be delivered directly to the small tumors while avoiding healthy brain tissue. The term radiosurgery is used because the destruction is so precise that it acts almost like a surgical knife. Some studies suggest that stereotactic radiosurgery improves survival, even in patients with the highly aggressive glioblastoma multiforme brain cancer. The procedure is being tested to boost standard radiotherapy.

Benefits of Stereotaxy. There are numerous benefits for stereotaxy:

Stereotaxy allows precisely focused, high-dose beams to be delivered to gliomas less than 1.25 inch in diameter.
Investigators have found that stereotactic radiosurgery can help them reach small tumors located deep in the brain that were previously considered inoperable.
Sometimes with stereotaxy only a single treatment may be needed.
Unlike traditional radiotherapy, stereotactic radiotherapy can be repeated, so it is useful for recurrent tumors when a patient has already received standard radiation treatments.
Combining stereotaxy with techniques that gauge speech and other mental functions in patients who are awake during the procedure can allow removal of brain tissue with a lower risk for complications in areas that affect such functioning.

The Planning Procedure. Stereotactic radiosurgery usually begins with a series of steps designed to plan the radiation target:

First, the patient is given a local anesthetic. In the standard operation, the patient's head must be totally immobilized by screwing a device known as a stereotactic frame into the patient's skull. (The frame procedure is effective only on brain tumors that have regular margins.) The frame is removed as soon as the whole procedure has been completed (about 3 - 4 hours).
A three-dimensional map, usually using magnetic resonance imaging (MRI) scans, is made of the patient's brain.
A computer program calculates dosage levels and specific areas for radiation targeting.

Advanced imaging techniques are now allowing frameless stereotaxy, which eliminates the frame and may be effective on more tumors. For example, high-field interventional MR imaging (iMRI) uses a guidance system based on cruise-missile technology to calculate the slightest variations in movements of the head and the location of the tumor relative to these movements. These calculations are then used to target the radiation beams directly on the tumor, even if the patient's head is moving slightly.

Delivery of Radiation Beams. Once the preliminary planning stage has been completed, treatment begins. Several advanced machines, such as the gamma knife, adapted linear accelerator (LINAC), and cyclotron, are being used with stereotaxy and can deliver very focused beams of radiation. Actual treatment takes 10 minutes to 1 hour.

The gamma knife uses gamma rays that are sent from multiple points to converge at a single point on the tumor. Although each gamma-ray beam is very low dosage, when the beams converge, the intensity and destructive power is very high. The gamma knife is limited to very small tumors and so is generally useful as a booster after standard radiation, surgery, chemotherapy, or combinations.
The linear accelerator (LINAC) produces photons (positively-charged atomic particles) in patterns that are matched to the tumor shape. The patient is positioned on a bed that can be moved to allow flexible positioning. It allows treatment over multiple sessions of small doses (fractionated stereotactic radiotherapy), instead of a single session. This means that larger tumors can be treated.
The cyclotron is basically an atom smasher, which produces protons that can be directed toward the tumor. As part of this procedure, some researchers are using boron neutron capture therapy (BNCT). BNCT employs intravenous administration of a boron compound, which is picked up more selectively by tumor cells than by normal brain tissue. The cyclotron delivers a single dose of radiation that triggers the release of high-energy particles from the boron to destroy nearby tumor cells. The cyclotron is available only in a very few locations, and there have been few trials to date.

Researchers are studying drugs that may be used along with radiation to increase the effectiveness of the treatment.

Radioprotectors. Drugs such as amifosistine (Ethyol) may protect healthy cells during radiation.

Radiosensitizers. Drugs such as fluorouracil (5-FU) and cisplatin (Platinol) may help make cancerous cells more sensitive to radiation.

Common Side Effects. Side effects of radiotherapy may vary depending on the tumor type and radiation treatment. Side effects may include hair loss, fatigue, and nausea and vomiting. Skin irritation and sensitivity may develop in the areas being treated. To prevent further irritation, avoid scratching or rubbing, avoid direct sunlight and heating pads, and do not attempt to treat the symptoms yourself. (Ask your doctor or radiation therapist for advice.) Brain swelling (edema) is another common radiotherapy side effect, which can sometimes cause an increase in brain tumor symptoms. Edema can be treated with steroids.

Tissue Injury. Radiation necrosis (total destruction of nearby healthy tissue) occurs in about 25% of patients treated with intensive radiation. Radiation necrosis can cause brain swelling and reduction in mental functions. The condition is treated with steroids. If steroids prove ineffective, surgery may be required to remove the damaged tissue.

New Tumors. Radiation therapy for childhood cancer is the most important risk factor for developing new brain and spinal column tumors, according to a 2006 study. The risk appears greatest for children who received radiation therapy before age 5. Researchers found that the risk of second primary tumors increased in relation to the radiation dose used to treat the first cancer.

Stroke. Survivors of childhood brain tumors who were treated with high doses of cranial radiation (especially doses greater than 50Gy) may be at increased risk of having a stroke later in life. In a study of nearly 2,000 brain tumor survivors, the average length of time from cancer diagnosis to stroke was 14 years.

Chemotherapy

Chemotherapy involves the use of drugs to kill or alter cancer cells. Chemotherapy is not an effective initial treatment for low-grade brain tumors, mostly because standard drugs cannot pass through the blood-brain barrier, the functional system that protects the brain by preventing certain molecules from reaching the central nervous system. In addition, not all types of brain tumors respond to chemotherapy. In general, chemotherapy for brain tumors is usually administered following surgery or radiation therapy.

The type of drug determines how it is administered. "Systemic delivery" drugs, which pass to the brain from the bloodstream, may be given by mouth, injected into a vein through an IV, or injected into an artery or a muscle. "Local delivery" drugs are placed within or around the brain tumor.

Scientists are working on several approaches to overcome the blood-brain barrier. Newer delivery methods include:

Interstitial chemotherapy uses disc-shaped polymer wafers (known as Gliadel wafers) soaked with carmustine, the standard chemotherapeutic drug for brain cancer. The surgeon implants the wafer directly into the surgical cavity after a tumor is removed.
Intrathecal chemotherapy delivers chemotherapeutic drugs directly into the spinal fluid.
Intraarterial chemotherapy delivers high-dose chemotherapy into arteries in the brain using tiny catheters. In one study, this approach was used within 2 weeks of radiotherapy in patients with high-grade astrocytomas, and the survival rates for glioblastoma multiforme tripled (20 months) compared to those who had chemotherapy and radiation at the same time.
Convection-enhanced delivery (CED) involves placing catheters into the brain tumor or nearby brain tissue to deliver slowly and continuously a cancer drug over several days.

Many different drugs, and drug combinations, are used for chemotherapy. Standard ones include:

Temozolomide (Temodar). Temozolomide, the first new drug approved for brain tumors in several decades, is taken by mouth as a pill. Temozolomide was first approved in 1999 for adult patients with anaplastic astrocytoma that did not respond to other treatments. In 2005, it was approved for use during and after radiation therapy for patients newly diagnosed with glioblastoma multiforme. The current first-line treatment for patients with glioblastoma is combined radiotherapy and temozolomide, followed by monthly doses of temozolomide after radiation treatment ends. A 2005 study, published in the New England Journal of Medicine, reported that adults with newly diagnosed glioblastoma who received temozolomide during and after radiation therapy had a higher rate of 2-year survival than patients who received radiation alone. A 2007 study in Neurology suggested that temozolomide works best for patients who are missing a particular gene (1p/19q). Temozolomide’s side effects are relatively minor, but may include constipation, nausea and vomiting, fatigue, and headache.

Carmustine (BCNU, BiCNU). Carmustine is used to treat many types of brain tumors, including glioblastoma, medulloblastoma, and astrocytoma. Carmustine is usually administered into the vein by IV. It can also be delivered through a wafer implant (Gliadel), which is surgically placed into the brain cavity after tumor removal. If carmustine is administered intravenously, side effects may include nausea and vomiting, fatigue, respiratory problems, and lung scarring (pulmonary fibrosis). Intravenous carmustine may cause bone marrow impairment, which results in decreased production of blood cells (a condition called myelosuppression). If carmustine is delivered through a wafer, side effects may include seizures, brain swelling, and infection within the brain cavity.

PCV Drug Regimen. PCV is an abbreviation for a chemotherapy regimen that combines procarbazine (Matulane), lomustine (CCNU), and vincristine (Oncovin). PCV is commonly used to treat oligodendrogliomas and oligoastrocytomas. The drugs may also be used alone or in other combinations. Procarbazine and lomustine are taken by mouth. Vincristine is given by either injection or IV. These drugs can cause significant side effects, including a drop in blood cell counts, nausea and vomiting, constipation, fatigue, and mouth sores. Procarbazine can cause high blood pressure when taken with foods high in tyramine. Patients should avoid foods such as beer, red wine, cheese, chocolate, processed meat, yogurt, and certain fruits and vegetables.

Platinum-Based Drugs. Cisplatin (Platinol) and carboplatin (Paraplatin) are standard cancer drugs that are sometimes used to treat glioma, medulloblastoma, and other types of brain tumors. These drugs are delivered by IV. In addition to nausea and vomiting, carboplatin can cause hair loss, and cisplatin can cause muscle weakness.

Patients with brain tumors, especially tumors that are in advanced stages, should consider enrolling in clinical trials. Many clinical trials are conducted through academic medical centers. Some promising areas of drug research include:

Other Chemotherapy Drugs. Researchers are investigating whether drugs used to treat other types of cancer may have benefits for brain tumors. These drugs include tamoxifen (Nolvadex) and paclitaxel (Taxol), which are used to treat breast cancer; topotecan (Hycamtin), which is used to treat ovarian and lung cancers; and vorinostat (Zolinza), which is approved for treatment of cutaneous T-cell lymphoma. Research presented at the 2007 meeting of the American Society of Clinical Oncology indicated that vorinostat may help patients with glioblastoma multiforme. Irinotecan (Campath) is another cancer drug that is being studied in combination treatment.

Molecular Targeted Therapy Drugs. One of the most promising developments in cancer treatment research has been the emergence of so-called "targeted therapies." Traditional chemotherapy drugs can be effective, but because they do not distinguish between healthy and cancerous cells their generalized toxicity can cause severe side effects. Targeted therapies work on a molecular level by blocking specific mechanisms associated with cancer cell growth and division. Because they selectively target cancerous cells, they may induce less severe side effects. In addition, these drugs hold the promise of creating options for more individualized cancer treatment based on a patient's genotypes.

Promising targeted therapies for brain tumors include:

Anti-angiogenesis drugs block molecules involved with the growth of blood vessels that feed the tumor (a process called "angiogenesis," which is particularly important in the growth of glioblastomas.) These drugs starve tumors of vital nutrients and oxygen. Bevacizumab (Avastin) is being studied in combination with irinotecan for treatment of recurrent malignant gliomas. Bevacizumab targets vascular endothelial growth factor (VEGF), a specific angiogenesis growth factor. Cediranib (Recentin, AZD2171) is another VEGF inhibitor. In 2007 clinical trials, cediranib appeared to help make recurrent glioblastomas more responsive to chemotherapy and radiation treatment.
Tyrosine kinase inhibitor drugs block proteins involved in tumor cell growth and production. Drugs that specifically target epidermal growth factor receptors (EGFR) are a type of tyrosine kinase inhibitor of special interest in brain tumor research. These drugs include erlotinib (Tarceva), imatinib (Gleevac), and gefitinib (Iressa).
Farnesyl protein transferase inhibitors, such as tipifarnib (Zarnestra) and lonafarnib (Sarasar), are drugs that target a protein involved in the functioning of the cancer-causing Ras protein. Lonafarnib is being studied in combination with temozolomide, and tipifarnib in combination with radiation therapy.
MTOR inhibitors target other enzymes involved in cell growth and replication. Everolimus (RAD-001) is being studied for glioblastoma multiforme and astrocytoma. Everolimus is related to rapamycin (Siroliumus) and tacrolimus (Prograf), which are also being investigated for brain tumor treatment. These drugs are commonly used to suppress the immune system to prevent rejection after organ transplantation.

Other Treatments

Researchers are testing several drugs that target specific mechanisms associated with brain cancer. Combinations of some of these drugs, with or without standard chemotherapy and radiotherapy, may prove to be more effective than the use of any one treatment. It should be noted that none of these drugs at this time are producing cures, although some are improving survival.

Immunotherapy aims at using modalities that boost the patient's own immune system's ability to seek out and destroy cancerous cells.

Radioimmunotherapy with Monoclonal Antibodies. Radioimmunotherapy is showing special promise as a treatment approach to brain tumors. It typically uses monoclonal antibodies (MAbs), genetically engineered drugs designed to work against a specific target. MAbs are bound with radioactive substances and delivered directly into the brain and sometimes into the tumor. The MAbs are specifically designed to lock with the surface of certain cells in the tumor. Once they do so, the radioactive substances destroy the cell. The approach is essentially mini-radiation therapy without the damage or severe side effects of standard radiation treatments. Numerous different radioimmunotherapies are being investigated, and trials of some are reporting improved survival rates in high-grade gliomas. Some doctors believe this approach could prove to be the most effective therapy against these cancers.

Interleukins. Interleukins are natural proteins created by the immune system. Certain tumor cells carry receptors for specific interleukins, which are being investigated for a possible therapeutic role. For example, some drugs combine an interleukin with a drug that is toxic to cancer cells. The interleukin locks onto the receptor on the cancer cell, and the toxic chemical enters the tumor with the intent to kill it. Some interleukins are also being investigated alone for their own tumor-cell killing properties.

Tumor Vaccines. Tumor vaccines are being created, in which tumor cells are removed from the patient and inactivated. When the tumor cells are transferred back to the patient, they are harmless but can elicit a powerful immunologic response against the tumor. Vitespan (Oncophage) is a tumor vaccine that is showing promise against recurrent high-grade glioma, according to preliminary results from early trials presented at the 2007 annual meeting of the American Association of Neurological Surgeons.

Much research is focusing on drugs that block small molecules involved with the growth of blood vessels that feed the tumor (a process called angiogenesis). Such drugs, when effective, would starve tumors of vital nutrients and oxygen. Angiogenesis is particularly important in the growth of glioblastomas, the most malignant brain tumors. Of particular promise are drugs that inhibit enzymes called tyrosine kinase, farnesyl protein transferase, and matrix metalloproteinase, which play critical roles in angiogenesis.

Farnesyl Protein Transferase Inhibitors. Farnesyl protein transferase inhibitors, such as tipifarnib, also called R115777 (Zarnestra) and lonafarnib (Sarasar), are drugs in a new class that block a mutated gene called the Ras gene, which is responsible for about 30% of cancers. Lonafarnib is in early trials in combination with temozolomide. Tipifarnib is also currently in early trials and may prove to be effective.

Tyrosine Kinase Inhibitors. Drugs that target growth factor receptors, such as tyrosine kinase, interfere with the pathway leading to angiogenesis. Some tyrosine kinase inhibitors -- including erlotinib (Tarceva), imatinib (Gleevac), gefitinib (Iressa), and others -- are being investigated in early trials for brain tumor treatment. Side effects include rash, diarrhea, nausea and vomiting. Some of these drugs may reduce white blood cell count or cause liver damage. Researchers are trying to identify biomarkers that could help predict which patients would best respond to tyrosine kinase inhibitor therapy.

Matrix metalloproteinase Inhibitors. Matrix metalloproteinase is an important enzyme in angiogenesis. Inhibitors of these enzymes, including marimastat, metastat, and prinomastat, are in early trials. Marimastat has been studied and has shown some benefits in early trials for patients with recurrent glioblastoma and anaplastic gliomas, particularly in combination with temozolomide.

Phophoinositide 3-Kinse (Pi3K) Inhibitors. Rapamycin and its analog (CCI-779) inhibit Pi3K, an enzyme involved in cell growth. Early trials using CCI-779 are underway. (Another rapamycin analog, everolimus, has different effects but is also being studied for its actions in inhibiting cell growth.)

Other Drugs that Block Angiogenesis. Thalidomide was one of the first drugs used to inhibit angiogenesis and has undergone several trials. There is some evidence that it may work more effectively for metastasized brain tumors than primary tumors. Other drugs in early trials with various effects on tumor growth include suramin, cilengitide, semaxanib, PTK787, and atrasentan.

Retinoids. Retinoids are vitamin A derivatives and act as differentiating drugs in cancer treatments. That is, they can convert immature, dividing tumor cells into mature cells, stopping tumor growth. Studies suggest that they have little benefits as single drugs. Combination with radiotherapy and other drugs may hold promise.

Inactivated Viruses. Investigators are finding that certain genetically inactivated viruses, such as the poliovirus or herpes virus, may prove to be valuable fighters of brain cancers. Such viruses can enter cells and destroy them but do not pose any danger for infection. For example, one specially designed herpes virus targets the enzyme thymidine kinase (an enzyme that promotes tumor growth). Some researchers believe that a combination of this virus with retinoids may be effective with few serious side effects. Other viruses are being investigated. A drug based on this model is years away, however.

Immunotoxins. Drugs called immunotoxins use natural toxins to kill malignant brain cells.

Drugs that use diphtheria toxins, including TransMID-107R and DAB(389)EGF), are the first immunotoxins to show some promise. Clinical trials are investigating them for gliomas and metastatic brain cancers. Other toxins under investigation include irofulven (a mushroom toxin) and chlorotoxin (a substance derived from scorpions).

Taurolidine. Taurolidine is a unique drug that prevents tumor formation and growth in animals. An early clinical trial in patients with high-grade gliomas is under way.

Protein-Blocking Drug. Another development is the discovery of a protein called BEHAB (Brain-Enriched Hyaluronan Binding Protein). BEHAB is produced only by invasive glioma tumor cells, not by normal brain tissue or noninvasive tumor cells. Breakdown of BEHAB releases a substance called HABD (hyaluronan-binding domain), which appears to give glioma cells the ability to invade other areas of the brain. Both BEHAB and HABD represent potential targets for new therapies.

Chemotherapy destroys not only cancer cells but also healthy cells, including special blood cells in the bone marrow called stem cells. Stem cells are immature cells from which all blood cells develop. Transplantation procedures using bone marrow or stem cells allow high-dose chemotherapy to be administered while protecting blood cells. The procedures are being tested for patients with recurrent brain tumors, such as medulloblastoma, primitive neuroectodermal tumors, and germ cell tumors. A 2003 study reported long-term survival in some patients who underwent this procedure

Photodynamic therapy uses a special drug (Photofrin) that is absorbed by the tumor and causes the cancer cells to become fluorescent when a laser is directed at them. It is being investigated in trials in combination with other treatments. A 2003 study reported encouraging results, notably in patients with recurring glioblastoma multiforme. In the study, more than half of these patients survived for at least a year.

Treatment of Complications

Some tumors, particularly medulloblastomas, interfere with the flow of cerebrospinal fluid and cause hydrocephalus (accumulation of fluid in the skull). This causes a build-up fluid in the ventricles (the cavities) in the brain. Symptoms include nausea and vomiting, severe headaches, lethargy, difficulty staying awake, seizures, visual impairment, irritability, and tiredness.

The ventricles of the brain are hollow chambers filled with cerebrospinal fluid (CSF), which supports the tissues of the brain.

Corticosteroids (commonly called steroids) such as dexamethasone (Decadron), prednisolone, and prednisone are used to treat hydrocephalus. Side effects include high blood pressure, mood swings, increased risk of infection, stronger appetite, facial swelling, and fluid retention.

Human corticotropin-releasing factor (hCRF), a naturally occurring neurohormone, appears to possess substantial anti-swelling properties and thus has been proposed as an alternative to corticosteroids in brain edema, with potentially fewer side effects. A hCRF drug called Xerecept is currently in clinical trials.

A shunt procedure may be performed to drain fluid. Shunts are flexible tubes used to reroute and drain the fluid.

Seizures are common in brain tumor cases, with younger patients having higher risks than older ones. Anti-epileptic medications, such as carbamazepine or phenobarbital, may treat seizures and are helpful in preventing recurrence. These drugs are not useful in preventing a first seizure, however, and they should not be used routinely to treat patients with newly diagnosed brain tumors. Anti-seizure medications should be used only for patients who are experiencing seizures. Despite these guidelines, a 2005 study in the Journal of the American Medical Association reported that nearly 90% of patients with newly diagnosed malignant glioma are treated with anti-epileptic drugs, although only 32% of the patients actually have seizures. Anti-seizure medications can interact with some of the chemotherapies used to treat brain cancers, including paclitaxel, irinotecan, interferon, and retinoic acid. Patients should discuss these interactions with their doctors.

Antidepressants are very useful for treating the emotional side effects of this disease. However, according to a 2005 Journal of the American Medical Association study, only 8% of patients with malignant gliomas receive antidepressant medication even though over 90% report depressive symptoms. Support groups can also have great benefit for both patients and families.

Resources

www.abta.org -- American Brain Tumor Association
www.cbtf.org -- Children's Brain Tumor Foundation
www.virtualtrials.com -- Musella Foundation for Brain Tumor Research and Information
www.braintumor.org -- National Brain Tumor Foundation
www.neurosurgery.org -- American Association of Neurologic Surgeons
www.cancer.org -- American Cancer Society
www.cancer.gov -- National Cancer Institute
www.asco.org -- American Society for Clinical Oncology
www.cancer.gov/clinicaltrials -- Find clinical trials
www.radiologyinfo.org -- RadiologyInfo
www.plwc.org -- People Living with CAncer

References

Bowers DC, Liu Y, Leisenring W, McNeil E, Stovall M, Gurney JG, et al. Late-occurring stroke among long-term survivors of childhood leukemia and brain tumors: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2006 Nov 20;24(33):5277-82. Epub 2006 Nov 6.

Dunlap SM, Celestino J, Wang H, Jiang R, Holland EC, Fuller GN, et al. Insulin-like growth factor binding protein 2 promotes glioma development and progression. Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11736-41. Epub 2007 Jul 2.

Flint-Richter P, Sadetzki S. Genetic predisposition for the development of radiation-associated meningioma: an epidemiological study. Lancet Oncol. 2007 May;8(5):403-10.

Kaloshi G, Benouaich-Amiel A, Diakite F, Taillibert S, Lejeune J, Laigle-Donadey F, et al. Temozolomide for low-grade gliomas: predictive impact of 1p/19q loss on response and outcome. Neurology. 2007 May 22;68(21):1831-6.

Keime-Guibert F, Chinot O, Taillandier L, Cartalat-Carel S, Frenay M, Kantor G, et al. Radiotherapy for glioblastoma in the elderly. N Engl J Med. 2007 Apr 12;356(15):1527-35.

Neglia JP, Robison LL, Stovall M, Liu Y, Packer RJ, Hammond S, et al. New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2006 Nov 1;98(21):1528-37.

Sharma MK, Mansur DB, Reifenberger G, Perry A, Leonard JR, Aldape KD, et al. Distinct genetic signatures among pilocytic astrocytomas relate to their brain region origin. Cancer Res. 2007 Feb 1;67(3):890-900.

Vredenburgh JJ, Desjardins A, Herndon JE 2nd, Dowell JM, Reardon DA, Quinn JA,et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 2007 Feb 15;13(4):1253-9.

Review Date:
11/1/2007
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

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adam.com

Looking For Motivation: Use Your Imagination

FitSugar — Thu, 03 Sep 2009 14:30:24 -0700

We all hit slumps, when we either don't want to exercise or working out just doesn't feel as good as it used to. When you hit the wall, using your imagination can help motivate you to get up and get moving.

Imagining your workout, be it running or rowing, activates the same part of your brain as actually doing the activity. Jumping into your workout is considerably less difficult when you harness this visualization. Picture yourself barreling up the hills then skipping down the other side, and your motivation will soon follow. Mentally reviewing the technique of your sport can help work out the kinks that are causing your discomfort or hurting your performance. Use your brain and get moving.

Epilepsy

FitSugar — Wed, 08 Oct 2008 17:35:12 -0700

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

Parkinson's disease

FitSugar — Wed, 08 Oct 2008 17:35:13 -0700

In This Report

Highlights
Introduction
Symptoms
Risk Factors
Complications
Diagnosis
Treatment
Levadopa (L-dopa)
Other Medications
Surgery
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

In 2007, the FDA approved the first skin patch drug for treatment of Parkinson’s disease. Transdermal rotigotine (Neupro) is a dopamine agonist drug that may help improve symptoms of early-stage Parkinson’s disease. The patch is applied daily.
Rivastigimine (Exelon), an Alzheimer’s disease drug, was approved in 2006 for treatment of mild-to-moderate dementia associated with Parkinson’s disease.

Drug Withdrawal

In 2007, the FDA withdrew the dopamine agonist pergolide (Permax) from the market due to safety concerns. Several articles published in 2007 in the New England Journal of Medicine indicated that pergolide and a similar drug, cabergoline (Dostinex), are associated with heart valve problems. Cabergoline is not approved in the U.S. for treatment of Parkinson’s disease.

Dietary Supplements

In 2007, the U.S. National Institutes of Health launched a large-scale clinical trial to study whether creatine may help slow the progression of Parkinson’s disease. Creatine is a nutritional supplement that is sometimes used to enhance exercise performance.
Coenzyme Q10, an antioxidant dietary supplement, does not help improve Parkinson’s disease symptoms, according to a study published in 2007 in the Archives of Neurology.

Deep-Brain Stimulation

Deep-brain stimulation outperformed drug therapy in a randomized trial comparing these two treatment approaches. In a study published in 2006 in the New England Journal of Medicine, patients who received deep-brain stimulation had better symptom and quality of life improvement than those who were treated with only medications. However, more serious side effects were reported in the deep-brain stimulation group. Deep-brain stimulation is a surgical technique that involves implanting electrodes in a target area of the brain.

Introduction

Parkinson's disease (PD) is a slowly progressive disorder that affects movement, muscle control, and balance. Parkinson's disease is referred to as idiopathic, which means that the cause is unknown. This term distinguishes the primary disease from parkinsonism, which are the symptoms occurring from a known cause. In addition to its effects on motor control, Parkinson's disease is now recognized as a broader condition that can include cognitive and behavioral disturbances, sleep disorders, speech difficulties, and other problems.

Parkinson's disease occurs from the following process in the brain:

PD develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell mass known as the substantia nigra.

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.

Nerve cells in the substantia nigra send out fibers to the corpus stratia, gray and white bands of tissue located in both sides of the brain.
There the cells release dopamine, an essential neurotransmitter (a chemical messenger in the brain). Loss of dopamine in the corpus stratia is the primary defect in Parkinson's disease.

Dopamine. Dopamine deficiency is the hallmark feature in PD. It is one of three major neurotransmitters known as catecholamines, which help the body respond to stress and prepare it for the fight-or-flight response. Loss of dopamine negatively affects the nerves and muscles controlling movement and coordination, resulting in the major symptoms characteristic of Parkinson's disease. Dopamine also appears to be important for efficient information processing, and deficiencies may also be responsible for problems in memory and concentration that occur in many patients.

Although it is clear that dopamine deficiency is the primary defect in Parkinson's disease, it is not clear what causes dopamine loss. The culprit is less likely to be a single cause than a combination of genetic and biologic factors, which are triggered by some environmental assault.

Other Changes. The PD disease process also appears to impair nerve endings in the heart to cause dysautonomia-- changes in the autonomic (also called sympathetic) nervous system. Such changes may impair the release of norepinephrine, a hormone that regulates blood pressure, pulse rate, perspiration, and other automatic responses to stress. Evidence suggests this may be responsible for the abrupt drops in blood pressure when standing that occur in PD. Further research is underway to determine if the loss of nerve terminals is confined to the heart or if it affects other organs as well.

Click the icon to see an animation about Parkinson's disease.

Apoptosis and Alpha Synuclein. Important research now suggests that three molecules are critical in the development of inherited PD: alpha synuclein, parkin, and ubiquitin, which all interact in the normal brain. Abnormally high levels of alpha synuclein, which is produced in dopamine-rich nerve cells, may play a central role. Normally, two other molecules, parkin and ubiquitin, are involved in the natural self-destruction of synuclein -- a natural process of programmed cell death called apoptosis. If this process goes awry, for instance, with a defective parkin gene, cell death fails to occur. If synuclein is not eliminated in these cells, it builds up and becomes toxic to dopamine. In such cases, synuclein accumulates in Lewy bodies, the deposits of fibrous tissue found in all patients with PD.

Another protein, beta amyloid, also increases the build-up of synuclein. Beta amyloid is a known factor in Alzheimer's disease, and may help explain the co-existence between Alzheimer's and Parkinson's disease in many patients.

Lewy Bodies. The fibrous deposits known as Lewy bodies are the hallmark signs of Parkinson's disease. They are found in the substantia nigra, the place in the brain where dopamine is first released. It is not clear whether Lewy bodies are the major killers of the nerve cells or whether they are simply a byproduct of the degenerative process. They are found not only in the brains of patients with Parkinson's disease but, in rare cases, may show up in cells in other parts of the body (the heart, intestine), causing severe disabling symptoms. These substances are also present in other diseases that cause dementia, such as Alzheimer's, and can occur in people without neurologic symptoms.

The Mitochondria and Oxygen-Free Radicals. Some research has observed that certain patients with PD have significantly low levels of complex I, an enzyme found in the mitochondria, sausage-like structures that are the primary source of energy within cells. Some theories suggest that low amounts of complex I may make nerve cells vulnerable to the assault of oxygen free radicals (also called oxidants). Oxidants are unstable molecules that bind to other molecules in the body. They are normally produced by the natural chemical processes in the body. If the body is subjected to environmental stresses, however, they can be over-produced. In excess, they can damage any cell, including nerve cells in the brain, and even interfere with their DNA.

NMDA Receptors. Also of interest in PD are processes that occur in an area of the brain called the subthalamic nucleus. Here, receptors known as glutamatergic N-methyl-D-aspartate (NMDA) become persistently overexcited and produce high levels of calcium ions within brain cells. This in turn leads to a cascade of events that trigger oxygen-free radicals and cell damage.

Immune Factors and the Inflammatory Response. An over-responsive immune system triggered by initial damage may also play a role in perpetuating Parkinson's disease. When the immune system becomes overactive, it produces excessive numbers of potent factors called cytokines, which cause inflammation and further injury in brain cells. Important cytokines under investigation are interleukin-1 and tumor necrosis factor.

Specific genetic factors appear to play a strong role in early-onset Parkinson's disease, an uncommon form of the disease. Research from the last several years suggests that multiple genetic factors may also be involved in late-onset Parkinson’s disease. Several important studies, published in 2005, lay the groundwork for potential genetic screening for this disease. Researchers identified the leukine-rich repeat kinase 2 (LRRK2) gene, located on a region of chromosome 12 known as PARK8, as a key gene involved in inherited forms of Parkinson’s. The researchers estimate that a single gene mutation in LRRK2 may be responsible for 5% of inherited Parkinson’s cases and about 2% of isolated cases.

Early Onset PD. The cases of genetic early-onset Parkinson's disease have most often been detected in specific family groups.

Defective genes that regulate the molecules alpha synuclein and parkin, which are important in the PD disease process, may be responsible for a number of early-onset cases. For example, genetic abnormalities the alpha synuclein protein have been detected in some early-onset Parkinson's patients of European descent.
The parkin gene may be the cause of many cases of early-onset Parkinson's in young adults. (Parkinson's cases associated with this mutation tend to progress slowly and respond well to treatment, even after years of symptoms. Dementia is also rare with this form.)

Late Onset PD. Two landmark studies published in the Journal of the American Medical Association provided the first evidence of a genetic link to late-onset Parkinson’s disease. In these 2001 studies, researchers found that regions on chromosomes 5, 6, 8, 9, and 17 were implicated with Parkinson’s. The parkin gene (located on chromosome 6) and the tau gene (located on chromosome 17) were both found in families that had late onset Parkinson’s. Parkin was previously thought to be responsible only for early-onset Parkinson’s, but this research identified it in families that had both early- and late-onset disease forms. These studies also bolstered the theory that Parkinson’s does have a genetic component and is not caused solely by environmental factors. A 2005 study found that a G2019S mutation in the LRRK gene, located on the PARK8 region of chromosome 12, was definitively associated with late-onset Parkinson’s disease in North American and European families.

Environmental toxins, infections, and other triggers can provoke excessive production in the body of oxygen free-radicals, damaging particles that may play a major role in the deterioration of nerve cells that lead to Parkinson's.

Infectious Organisms. Some research has identified immune factors that suggest a viral presence in the Lewy bodies and swollen nerve pathways of Parkinson's brains. Influenza and other potent viruses have long been known to be a cause of parkinsonism. In one well-known example, a major flu epidemic causing encephalitis in the early twentieth century left many of its victims with parkinsonism.

Environmental and Industrial Chemicals. Intense exposure to certain environmental and industrial chemicals is also being studied.

Pesticides and Herbicides. Some evidence implicates pesticides and herbicides as important factors in many cases of Parkinson's disease. A higher incidence of parkinsonism has long been noted in people who live in rural areas, particularly those who drink private well water or are agricultural workers. A large 2000 study found a strong link between high exposure to insecticides and herbicides at home and a 50 - 70% increase in risk of Parkinson's.
Other Chemicals. Intense exposure to other industrial chemicals and metals (manganese, copper, lead, iron, mercury, zinc, aluminum, and others) has also been linked with parkinsonism, a cause that is often reversible. The role of long-term exposure in the development of Parkinson's disease is unclear. High levels of iron content observed in critical parts of the brain in PD are under particular scrutiny.

Most, but not all, Parkinson's victims are elderly. Some studies indicate that the very elderly are not susceptible to the disease, indicating that the aging process itself is not the major player in the disease. Aging does appear to reduce the concentration of dopamine in structures called dopamine transporters, which carry the neurotransmitter back and forth between nerve cells. Some researchers posit that any excessive stress on these transporters might trigger Parkinson's disease in the aging, and more vulnerable, brain.

Symptoms

Parkinson's disease (PD) symptoms often start with tremor, which may occur in the following ways:

Tremors may first be only occasional, starting in one finger and spreading over time to involve the whole arm. The tremor is often rhythmic, 4 - 5 cycles per second, and frequently causes an action of the thumb and fingers known as pill rolling.
Tremors can occur when the limb is at rest or when it is held up in a stiff unsupported position. They usually disappear briefly during movement and do not occur during sleep.
Tremors can also eventually occur in the head, lips, tongue, and feet. Symptoms can occur on one or both sides of the body. In one study, 44% of patients reported experiencing internal tremors lasting less than half an hour, but occurring several times a week.

In younger patients tremor is usually predominant and often suggests a less aggressive form of the disease. Some evidence suggests that tremor in PD may occur from mechanisms in the brain that are different from those that cause other PD symptoms.

A number of PD symptoms involve motor impairment caused by the abnormalities in the brain that regulate movement:

Slowness of motion (bradykinesia) is one of the classic symptoms of Parkinson's disease. Patients may eventually develop a stooped posture and a slow, shuffling walk. The gait can be erratic and unsteady. After a number of years, muscles may freeze up or stall, usually when a patient is making a turn or passing through narrow spaces, such as a doorway.
Intestinal motility (the ability to swallow, digest, and eliminate) may slow down, causing eating problems and constipation.
Muscles may become rigid (akinesia). This symptom often begins in the legs and neck. Muscle rigidity in the face can produce a mask-like, staring appearance.
Motor abnormalities that limit action in the hand may develop in late stages. Handwriting, for instance, often becomes diminutive.
Normally spontaneous muscle movements, such as blinking, may need to be done consciously.

The traditional view of Parkinson's disease is shifting to reflect growing awareness that it is much more than a motor disease. Many non-motor components and their treatments are now under study. The following symptoms should be carefully monitored by doctors and caregivers:

Depression is the most common psychiatric problem associated with PD, affecting about 40% of patients. Because depression is a common problem in older people, it is likely not to be recognized as a symptom.
Anxiety affects about 30% of patients.
Dementia and paranoia are more common than previously understood.
Orthostatic hypotension -- some patients experience a sudden drop in blood pressure when they stand. This can cause dizziness and fainting.
Changes in sensations of temperature, hot flashes, and excessive sweating.
Daytime sleepiness and other sleep disorders are common.

Risk Factors

Parkinson's disease affects about 3% of Americans over 65 years old. Experts estimate that this percentage could double in the next 30 - 40 years. The symptoms of parkinsonism (tremor, gait disturbance, bradykinesia, and rigidity) occur in even more people, estimated to be 8 million over age 65. In a study that included very mild symptoms, parkinsonism occurred in about 15% of people 65 - 74 years of age, about 30% in those 75 - 84, and over half of people older than age 85.

The average age of onset of Parkinson's disease is 55. About 10% of Parkinson's cases are in people younger than 40 years old. Older adults are at higher risk for both parkinsonism and Parkinson's disease. There is some evidence, however, that the risk declines significantly after age 75 and that the very elderly are at low risk.

Some research indicates that men may face up to twice the risk as women. Estrogen may offer some protection for women up until menopause. A 2001 study, for example, reported a higher rate of Parkinson's disease in women who had undergone hysterectomy. Other studies suggest that the disease also progresses more rapidly in men than women. Older women seem to be more at risk for gait disturbance and men for rigidity and tremor.

People with siblings or parents who developed Parkinson's at a younger age are at higher risk for Parkinson's disease, but relatives of those who were elderly when they had the disease appear to have an average risk.

African- and Asian-Americans have a lower risk than Caucasians. Some evidence suggests that non-Caucasians may be more vulnerable to an atypical form of PD, which causes early impairment in thinking and has a poor response to levodopa, the primary PD treatment.

Increasing weight gain in middle age was associated with a higher risk of PD in a 2002 study.

Complications

Parkinson's disease (PD) is not fatal, but it can reduce longevity. The disease progresses more quickly in older than younger patients, and may lead to severe incapacity within 10 - 20 years. Older patients also tend to experience freezing and greater declines in mental function and daily functioning than younger people. If PD starts without signs of tremor, it is likely to be more severe than if tremor had been present. Having other family members with PD does not appear to have any effect on the severity of the disease.

Parkinson's disease can seriously impair the quality of life in any age group. The physical and emotional impact on the family should not be underestimated as the patient becomes increasingly dependent on their support.

Treatment advances are increasingly effective in alleviating symptoms and even slowing progression of the disease. Taking many of the medications over time, however, can produce significant side effects. Newer drugs may help reduce these occurrences.

The negative effect of overall motor and muscle impairment on daily life can be considerable. Some motor complications can be life-threatening.

Disturbed gait and unstable posture are common and serious problems in elderly patients, since they increase the risk for falling and injury. Some studies have suggested that the appearance of these symptoms early in the course of the disease predict a faster decline than having tremor as the predominant symptom.
Swallowing problems (dysphagia). The presence of dysphagia is associated with shorter survival time. Motor impairment of the muscles in the throat not only impairs swallowing but it also poses a risk for aspiration pneumonia.
Constipation is a major problem and occurs both as a result of the disease and a side effect of its treatment. Laxatives, stool softeners, and other medications may be prescribed.
Bladder control and urinary incontinence are also important complications of PD.
Speech problems occur in more than 70% of patients, by some estimates. Speech difficulty can be caused by rigidity of the facial muscles, loss of motor control, and impaired breath control. Tone can become monotonous, words may be repeated over and over, or the rate of speech may even be very fast.

Depression is extremely common, affecting up to 40% of patients with Parkinson's. PD poses multiple threats on the emotional health:

The disease process itself causes changes in chemicals in the brain that affect mood and well-being.
The complications of its symptoms have a profound impact on daily life that can be emotionally devastating without help and support.
Some drug treatments (levodopa combined with a dopamine agonist) can cause compulsive behavior, such as gambling, shopping, and increased sexuality. Patients who have pre-existing tendencies to novelty-seeking behavior, or a family or personal history of alcohol abuse, may be more likely to develop compulsive gambling. Deep brain stimulus (DBS) surgery may also increase the risk for compulsive gambling in patients who have a history of gambling.

Impaired Thinking (Cognitive Impairment). Defects in thinking, memory, language, and problem solving skills may occur early on in untreated patients or late in the course of the disease. Medications may play a role in thinking problems. In one study, for example, patients with PD were slower in detecting associations, although (unlike in Alzheimer's disease) once they discovered them they were able to apply this knowledge to other concepts. After they were taken off medication, however, they had no problems with the tasks.

Dementia. Dementia is three to 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. PD marked by muscle rigidity (akinesia), rather than tremor, and early hallucinations also increase the risk for dementia. (Visual hallucinations can also occur in about a third of patients from PD medication.) Unlike in Alzheimer's, language is not usually affected in Parkinson's related dementia.

A number of other problems associated with Parkinson's disease affect daily life:

Vision Problems. Vision is also affected, including impaired color perception and contrast sensitivity. These problems progress and can impair motor functioning.

Sleep Disorders. Excessive daytime sleepiness and other sleep disorders are common in PD, both from the disease itself and from the drugs that treat it. In general, patients have a 25% higher risk for daytime sleepiness, including suddenly falling asleep, than patients with other neurologic diseases.

Restless legs syndrome, an irresistible urge to move the calves, which often occurs at night, affects many patients. However, Parkinson's disease itself does not seem to increase the risk for RLS. Nor does RLS early in life predispose to Parkinson's later on. The common connection between RLS and Parkinson's disease may derive from iron deficiencies that can play a role in both conditions.

Many patients also suffer from nighttime leg cramps. And, some of the medications cause vivid dreams as well as waking hallucinations.

Impaired Sexuality. Although Parkinson's disease and its treatments can cause compulsive sexual behavior, the disease can also affect patients' self-esteem and inhibit sexuality. This is an area not often studied but which is important for many patients' well-being. A 2000 study reported that not only did sexual dysfunction occur, but also affectionate touching and expression of feelings were reduced, even though both partners maintained a desire for intimacy.

Worsened Sense of Smell. The sense of smell is impaired in about 70% of patients.

Osteoporosis. Parkinson’s disease may increase the risk for low bone density and osteoporosis. Both men and women are at risk. Experts recommend that patients with Parkinson’s disease get tested for osteoporosis, especially if they have problems with walking.

Diagnosis

It is difficult to diagnose Parkinson's in early stages. The disease is primarily diagnosed by its symptoms, and studies indicate that doctors make an incorrect initial diagnosis of Parkinson's disease in 8 - 35% of cases. Even neurologists have difficulties in correctly identifying the disease.

A medical and personal history should include any relevant symptoms as well as any medications taken, and information on exposure to environmental toxins.

Early Symptoms. Early treatment may help slow progression, so an early diagnosis of Parkinson's is highly desirable. Early symptoms are often mild, however, so Parkinson's disease can be missed, particularly in young adults. Repeated assessment of symptoms over time is important for improving the accuracy of diagnosis. Too often a younger person with Parkinson's may be diagnosed with mental illness, because the doctor associates the disease only with older people.

Parkinson's may be suspected in patients with the following symptoms:

Slowness and difficulty of movement. These are usually the first symptoms. The patient will be asked to walk and to get out of a chair, preferably a deep one. Early gait disturbance, however, often indicates a disease other than Parkinson's disease.
A tremor when their limb is relaxed. (As many as 25% of patients, however, will not have a tremor.)
Symptoms on one side of the body.

Later Symptoms. In later stages of Parkinson's disease, the symptoms are usually unmistakable, and the problem can often be diagnosed using simple physical tests and a medical and personal history.

The loss of smell is associated with loss of dopamine receptors in the brain. “Scratch and sniff” smell tests can help a doctor diagnose Parkinson’s disease. Smell tests can help differentiate Parkinson’s disease from other conditions with similar symptoms. Some patients with a very similar condition called multiple system atrophy will have a good initial response to levodopa, but it is not usually sustained.

Levodopa and apomorphine can confirm a diagnosis of Parkinson’s disease. If patients’ symptoms improve when they take these drugs, they likely have Parkinson’s, ruling out other neurological diseases.

According to 2006 guidelines from the American Academy of Neurology, there is not enough evidence to recommend for or against the use of imaging techniques such as computerized tomography (CT), magnetic resonance imaging (MRI), or positron-emission tomographic (PET) to diagnose PD.

When symptoms resemble Parkinson's disease but have an identifiable cause, the syndrome is known as parkinsonism. People who have parkinsonism, but not Parkinson's disease, often have additional neurologic symptoms. A number of conditions can also have similar or some of these symptoms.

Other Neurologic Conditions. Many medical conditions may cause symptoms of Parkinson's disease:

Hardening of the arteries (arteriosclerosis) in the brain can cause multiple small strokes, which can produce loss of motor control.

Click the icon to see an image of plaque in an artery.

Alzheimer's disease can be very similar. In one study 23% of people with Alzheimer's also met the criteria for Parkinson's disease. The two diseases often coexist, and research suggests that Alzheimer's and Parkinson's disease may sometimes share a common biologic origin, the accumulation of the protein alpha synuclein and Lewy bodies in the brain.
Lewy bodies variant (LBV), also called dementia with Lewy bodies, is a separate disease from both Alzheimer's and Parkinson's disease. It has similar symptoms to both but is marked by early dementia.
Encephalitis caused by influenza has been known to cause parkinsonism.
Primary progressive freezing gait is a progression condition, in which freezing gait occurs at the onset. Other Parkinson-like features, such as slow movement, often develop. Although very similar to PD, this condition does not respond to L-dopa or other PD medications.
Essential tremor, unlike the tremor of Parkinson's disease, often occurs in the head and voice and is usually worse during motion, as opposed to rest.
Progressive supranuclear palsy has similar symptoms, but involves less tremor and earlier rigidity, and it tends to affect both sides of the body symmetrically. Magnetic resonance imaging scans that measure parts of the midbrain may be a reliable method for distinguishing between PD and progressive supranuclear palsy.
Multiple system atrophy (previously called Shy-Drager syndrome) is a degenerative nerve disease that also affects movement and blood pressure and has many of the symptoms of Parkinson's disease. Some research suggests that a trial using the drug apomorphine may help differentiate between the two.
Other problems that may mimic Parkinson's disease include Wilson's disease, thyroid abnormalities, hydrocephalus, tumors, having the fragile X trait (but not the full disorder), and a number of degenerative neurologic diseases.

Drugs. Certain drugs or medications account for about 4% of all cases of parkinsonism. According to some studies, patients who experience drug-induced parkinsonism may actually be at an increased risk of developing Parkinson's disease later in life. A number of drugs can cause these symptoms, including antipsychotic and antiseizure drugs. Anyone with parkinsonism should discuss their medications with their doctor.

The American Academy of Neurology (AAN) recommends the Beck Depression Inventory or the Hamilton Depression Rating Scale to screen for depression in patients with Parkinson’s disease. The AAN recommends the MMSE and CAMCOG tests to screen for dementia. During these tests, the patient answers a series of questions.

Treatment

Drugs, physical therapy, and surgical interventions can manage Parkinson's disease. The goals of treatment for Parkinson's disease are to:

Relieve disabilities
Balance the problems of the disease with the side effects of the medications

Treatment is very individualized for this complicated disease. Patients must work closely with doctors and therapists throughout the course of the disease to customize a program suitable for their particular and changing needs. Patients should never change their medications without consulting their doctor, and they should never stop taking their medications abruptly.

The American Academy of Neurology recommends the following therapies for the initial treatment of Parkinson’s disease:

Levodopa (L-dopa). Levodopa, or L-dopa, has been used for years and is the gold standard for treating Parkinson's disease. The drug increases brain levels of dopamine. It is used in nearly all phases of the disease. The standard preparations (Sinemet, Atamet) combine levodopa with carbidopa, a drug that slows the breakdown of levodopa. Levodopa is better at improving motor problems than dopamine agonists but increases the risk of involuntary movements (dyskinesia).

Dopamine Agonists. Dopamine agonist drugs mimic dopamine to stimulate the dopamine system in the brain. These drugs include pramipexole (Mirapex), ropinirole (Requip), bromocriptine (Parlodel), and rotigotine (Neupro). The Food and Drug Administration (FDA) pulled the dopamine agonist pergolide (Permax) from the market in March 2007 over safety concerns that included potentially fatal heart valve damage.

Selegiline (Eldepryl) and rasagiline (Azilect). Selegiline is a monoamine oxidase B (MAO-B) inhibitor that may have some mild benefit as an initial therapy. However, unlike levodopa, it does not slow the progression of Parkinson’s disease. Another MAO-B inhibitor, rasagiline (Azilect), was approved in May 2006. Unlike selegiline, which needs to be taken by mouth twice a day, rasagiline needs to be taken only once a day.

Drug treatments for Parkinson disease do not consistently control symptoms. At certain points during the day, the beneficial effects of drugs wear off, and patients can experience a return of symptoms, such as uncontrolled muscular motor function, difficulty walking, and loss of energy. In 2006, the American Academy of Neurology (AAN) reviewed evidence for the various drugs used to treat “off time.” The AAN found that the following drugs had the strongest evidence for controlling off time symptoms:

Entacapone (Comtan) belongs to a class of drugs called catechol-o-methyl transferase (COMT) inhibitors. COMT inhibitors help prolong the effects of levodopa by blocking an enzyme that breaks down dopamine.
Rasagiline (Azilect) belongs to a class of drugs called monoamine oxidase (MAO) inhibitors. These drugs slow the breakdown of dopamine that occurs naturally in the brain and dopamine produced from levodopa.

The AAN also found good evidence for the dopamine agonists ropinirole (Requip) and pramipexole (Mirapex), and the COMT inhibitor tolcapone (Tasmar). Deep brain stimulation is a surgical treatment that may help improve motor fluctuations in some patients.

Both Levodopa and dopamine agonists can cause involuntary movements (dyskinesia). The AAN has not found any strong evidence to recommend any drug for treating dyskinesia. However, weak evidence suggests that the antiviral drug amantadine (Symmetrel) may help reduce stiffness and improve dyskinesia. There is also weak evidence that deep brain stimulation of the subthalamus area may be helpful.

Conditions associated with motor impairment and other symptoms of Parkinson's disease may require a variety of treatments.

Depression. Although depression is very common in PD, there have been surprisingly few controlled studies. Antidepressants used for PD include tricyclics, particularly amitriptyline (Elavil). Some studies have found that selective serotonin-reuptake inhibitors (SSRIs) -- which include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil) -- may worsen symptoms of Parkinson's. Doctors should monitor patients taking SSRIs.

Psychotic Side Effects. Studies indicate that clozapine (Clozaril) and quetiapine (Seroquel), antipsychotic drugs used to treat schizophrenia, may be the best drugs for treating psychosis in patients with Parkinson's disease. A similar drug, olanzapine (Zyprexa), should not be used for patients with PD because it can worsen their psychotic symptoms.

Dementia. The cholinesterase inhibitor drugs donepezil (Aricept) and rivastigmine (Exelon) are used to treat Alzheimer’s disease. Studies suggest that these drugs may also help treat dementia associated with Parkinson’s disease. In 2006, rivastigimine was approved for treatment of mild-to-moderate dementia associated with Parkinson’s disease.

Daytime Sleepiness. Modafinil (Provigil), a drug used to treat narcolepsy, is proving to be very helpful for patients with sleepiness related to their disease.

Drooling. In search of a simple solution for the problem of drooling, scientists have reported that injections of very small amounts of botulinum toxin effectively reduce saliva production and drooling. In such small amounts the toxin is safe.

Voice Loss. A relatively simple procedure using collagen injections in the neck appears to be a safe and effective method of improving the voice and speech disorders caused by PD. The procedure augments the collagen in the vocal fold and works best in patients who can still initiate speech. A 2001 study reported improvements that lasted from 2 - 7 months in 61% of patients.

Erectile Dysfunction. Sildenafil (Viagra) is proving to be very helpful for men who suffer from impotence from Parkinson's disease. However, the drug may worsen orthostatic hypotension, a side effect of some PD medications.

Eventually, symptoms such as stooped posture, freezing, and speech difficulties may not respond to drug treatment. (Total unresponsiveness is unlikely, however, even after 20 years of treatment.) The following approaches may be tried:

Simply increasing the dose of levodopa or its frequency raises an unacceptable risk of the distressing side effects. Some doctors have tried hospitalizing patients, totally withdrawing the levodopa, and then re-administering it. Benefits were seen for only a few months, however, and there were some dangerous risks to the process of withdrawal, including pneumonia and blood clots in the lungs.

An embolus is a blockage of an artery in the lungs by fat, air, tumor tissue, or blood clot.

Surgical treatments, including deep brain stimulation and pallidotomy, may help some patients.
Research is ongoing to develop drugs and procedures that will manage advanced disease and possibly even reverse the process.

Levadopa (L-dopa)

Levodopa, also called L-dopa, which is converted to dopamine in the brain, remains the gold standard for treating Parkinson's disease. The standard preparations (Sinemet, Atamet) combine levodopa with carbidopa, which improves the action of levodopa and reduces some of its side effects, particularly nausea. Levodopa can also be combined with benserazide (Madopar) with similar results, but Sinemet is almost always used in America. Dosages vary, although the preparation is usually taken in three or four divided doses per day. In 2004, the FDA approved a new oral form of carbidopa-levodopa (Parcopa) that dissolves on the tongue.

In general L-dopa has the following effects on Parkinson's disease:

It is most effective against rigidity and slowness.
It produces less benefit for tremor, balance, and gait.

In many patients, levodopa significantly improves the quality of life for many years. If symptoms do not improve after 2 - 3 months, one of the following reasons may account for the failure:

Other neurologic problems may be causing the symptoms.
Some patients have abnormalities in other brain sites that do not respond to L-dopa.
Sometimes patients are so depressed they cannot tell if the drug is beneficial or not. Only a series of physical examinations by the doctor will indicate that the drug is actually helping.

Studies suggest that levodopa may help slow disease progression and protect against brain cell degeneration.

The toxic effects of levodopa with or without carbidopa are considerable.

Physical Side Effects. The physical side effects are as follows:

Low blood pressure. Low blood pressure is a common problem during the first few weeks, particularly if the initial dose is too high. The addition of extra supplements of carbidopa reduces this effect to some degree. The patient should drink lots of fluids and possibly increase salt intake to maintain normal blood pressure.
Arrhythmia. In some cases the drug may cause abnormal heart rhythms.
Gastrointestinal effects. Stomach and intestinal side effects are common even with carbidopa. Taking the drug with food can alleviate the nausea. However, proteins interfere with intestinal absorption of levodopa, and some doctors recommend not eating any protein until nighttime in order to avoid this interference. The drug can also cause gastrointestinal bleeding.
Effects in the lung. Levodopa can cause disturbances in breathing function, although it may benefit patients who have upper airway obstruction.
Hair loss.

Psychiatric and Mental Side Effects. The major adverse effects of the drug are psychiatric. Patients taking levodopa, especially in combination with other drugs, can experience:

Confusion.
Extreme emotional states, particularly anxiety.
Vivid dreams.
Visual and possibly auditory hallucinations. The drug may even unmask dementia that had not been previously noticed.
Effects on learning. L-dopa appears to have mixed effects on learning. It may improve working memory. However, some evidence suggests that it impairs areas of the brain related to other learning functions and social behavior.
Sleepiness and sleep attacks.

Levodopa causes fewer psychiatric side effects than other drugs used for Parkinson's disease, including anticholinergics, selegiline, amantadine, and dopamine agonists. Because psychiatric side effects often occur at night, if they are severe some doctors recommend reducing or stopping the evening dose.

Within 4 - 6 years of treatment with levodopa, the effects of the drug in many patients begin to last for shorter periods of time (called the wearing-off effect) and the following pattern may occur:

Patients may first notice slowness (bradykinesia) or tremor in the morning before the next dose is due.
Less commonly, some experience painful dystonia, muscle spasms that can cause sustained contortions of various parts of the body, particularly the neck, jaw, trunk, and eyes and possibly the feet.
Patients must increase the frequency of levodopa doses. This puts them at risk for dyskinesia (the inability to control muscles), which usually occurs when the drug level peaks. Dyskinesia can take many forms, most often uncontrolled flailing of the arms and legs or chorea, rapid and repetitive motions that can affect the limbs, face, tongue, mouth, and neck. Dyskinesia is not painful, but it is very distressing.
In some people, eventually L-dopa is effective only for 1 - 2 hours and most patients start to experience motor fluctuations. In about 15 - 20% of patients such fluctuations become extreme, a phenomenon known as the on-off effect, which consists of unpredictable, alternating periods of dyskinesia and immobility. Sometimes the symptoms switch back in forth within minutes or even seconds. (The transition may follow such symptoms as intense anxiety, sweating, and rapid heartbeats.)

Reasons for the Wearing-Off Effect. Debate is ongoing about the cause of the wearing-off effect and dyskinesia. Some theories suggested for these effects are:

The disease progresses beyond the ability of levodopa to control it.
Some patients become tolerant to prolonged exposure to dopamine and, at the same time, the disease is progressing.
The brain's own dopamine neurons become incapable of storing dopamine. When the levodopa wears off, little or no natural dopamine remains.
Levodopa itself accelerates the disease by producing oxygen free radicals, unstable particles that increase injuries to the brain and dopamine degradation.

Preventing the Wearing-Off Effect. To reduce the effects of fluctuation and the wearing-off effect, it is important to maintain as consistent a level of dopamine as possible. Unfortunately, levodopa is poorly absorbed and may remain in the stomach a long time. A number of strategies are being developed to take care of these problems:

Some patients take multiple small doses on an empty stomach, crushing the pills and mixing them with a lot of liquid.
A liquid form of Sinemet may produce fewer fluctuations and a prolonged "on" time compared with the tablet.
A prolonged release version of levodopa and carbidopa (Sinemet CR) is also available to control fluctuations for some people. (Some evidence suggests that there is no actual difference in symptom control between the sustained and immediate release forms, but patients on Sinemet CR tend to experience a better quality of life.)

Other Medications

Selegiline (Eldepryl, Movergan, Zelepar), also known as deprenyl, is an antioxidant drug that blocks monoamine oxidase B (MAO-B), an enzyme that degrades dopamine. Until recently, selegiline was the drug most commonly used in early-onset disease and in combination with levodopa for maintenance. A major 2002 study reported, however, that although selegiline delays the need for L-dopa by a few months, it has no effect on long-term progression.

Rasagiline (Azilect), another MAO-B inhibitor, was approved in May 2006 for the initial treatment of Parkinson’s disease. It is used alone during early-stage PD and in combination with L-dopa for moderate-to-advanced PD. Unlike selegiline, which is taken twice a day, rasagiline is taken once a day.

Other Adverse Effects. MAO-B inhibitors may have severe side effects:

One of the most important side effects is orthostatic hypotension, particularly in people taking Sinemet plus selegiline. This condition is a sudden drop in blood pressure that causes dizziness and lightheadedness when a patient stands up. Orthostatic hypotension can also occur with other Parkinson's drugs.
Can cause high blood pressure (hypertension) if combined with drugs that increase serotonin levels -- such drugs include nearly every major antidepressant. Patients suffering from depression and taking selegiline should discuss all treatment options with their doctor.
Can also cause a dangerous increase in blood pressure if patients eat foods rich in the amino acid tyramine. Patients should avoid the following foods while taking selegiline or rasagiline and for 2 weeks after stopping medication: aged cheeses, air-dried meats, pickled herring, yeast extract, aged red wines, draft beers, sauerkraut, and soy sauce

Debate over Mortality Rates. Some major studies have reported higher mortality rates in patients with advanced PD. Such findings may be due to adverse effects on the heart and blood vessels. Although other studies have not reported lower survival rates, some experts believe that, given its modest effects, selegiline may be a poorer drug choice than others, particularly in patients with risk factors for heart disease.

Dopamine agonists stimulate dopamine receptors in the substantia nigra, the part of the brain in which Parkinson's is thought to originate. Dopamine agonists are effective in delaying motor complications during the first 1 or 2 years of treatment.

Newer Dopamine Agonists. The most commonly prescribed dopamine agonists are pramipexole (Mirapex) and ropinirole (Requip). They are used either alone or in combination with L-dopa. Pramipexole appears to work better and have fewer side effects than ropinirole.

Studies still report, however, that L-dopa is superior for improving motor function. In one study, motor function was no different in disease progression among all of the drugs by the third year of treatment. Recent research suggests that L-dopa is better at improving motor disability and dopamine agonists are better at reducing motor complications. L-dopa has a higher risk for dyskinesia side effects than dopamine agonists, but dyskinesia can also occur with dopamine agonists.

Side Effects. Side effects of pramipexole and ropinirole vary but can be severe and include:

Gastrointestinal side effects (nausea and constipation). Nausea can be controlled by drugs, such as domperidone.
Headache
Orthostatic hypotension (sudden drop in blood pressure upon standing up)
Nasal congestion
Nightmares, hallucinations, and psychosis (more severe than with L-dopa for both drugs)
Sudden sleep attacks. These can be very serious, particularly if patients are driving. (Sleep attacks may occur -- although less commonly -- with other PD drugs.)

Other Dopamine Agonists.

Specific dopamine agonists that contain ergot alkaloids include bromocriptine (Parodel), pergolide (Permax), cabergoline (Dostinex), and lisuride (Dopergin). As of 2007, bromocriptine is the only ergot dopamine agonist approved for Parkinson’s treatment in the United States. In January 2007, the New England Journal of Medicine (NEJM) published two studies indicating that pergolide and cabergoline are associated with heart valve damage. In March 2007, due to these safety concerns, the FDA withdrew pergolide from the U.S. market. Cabergoline and lisuride are not approved in the U.S. for Parkinson’s disease treatment but are used for this purpose in other countries. The NEJM studies did not find any heart valve problems associated with bromocriptine or lisuride.
Rotigotine transdermal (Neupro) is a dopamine agonist that is delivered through a skin patch that is changed daily. In 2007, the FDA approved rotigotine transdermal for treatment of symptoms of early Parkinson’s disease. It is the first skin patch approved for Parkinson’s disease. Side effects are similar to those of other dopamine agonists.
Apomorphine is a dopamine agonist used as a "rescue" drug in people experiencing on-off effects severe enough to require going off L-dopa for a few days. In 2004, the FDA approved apomorphine for treating off-time episodes of Parkinson’s disease. Apomorphine is given by injection. Because it causes severe nausea and vomiting, it must be taken with an anti-nausea drug.

Catechol-O-methyl transferase (COMT) inhibitors increase concentrations of existing dopamine in the brain. Entacapone (Comtan, Stalevo) is the current standard COMT inhibitor. (Stalevo combines entacapone and levodopa into a single pill.) It improves motor fluctuations related to the wearing-off effect and has shown good results in improving on time and reducing the requirements for L-dopa. If the patient does not respond to the drug within 3 weeks, it should be withdrawn. No one should withdraw abruptly from these drugs.

Side Effects. Side effects include:

Involuntary muscle movements
Mental confusion and hallucinations
Cramps, nausea, and vomiting
Insomnia
Headache
Urine discoloration (a harmless side effect but should be reported to the doctor)
Diarrhea
Less commonly, constipation, susceptibility to respiratory infection, sweating, dry mouth

Of major concern are reports of a few deaths from liver damage in patients taking the COMT inhibitor tolcapone (Tasmar). The drug has been taken off the market in many countries and is recommended in the U.S. only for patients who cannot tolerate another other drugs. Entacapone does not appear to have the same effects on the liver and does not require monitoring. A 2003 3-year study suggested that the drug is safe and effective over the long term. Still, patients should watch out for symptoms of liver damage, including jaundice (yellowish skin), fatigue, and loss of appetite.

Jaundice is a condition produced when excess amounts of bilirubin circulating in the bloodstream dissolve in the subcutaneous fat (the layer of fat just beneath the skin), causing a yellowish appearance of the skin and the whites of the eyes. With the exception of normal newborn jaundice in the first week of life, all other jaundice indicates overload or damage to the liver, or inability to move bilirubin from the liver through the biliary tract to the gut.

Anticholinergics were the first drugs used for PD, but have largely been replaced by dopamine drugs. They are generally used only against tremor in the early stages. They are not as effective against bradykinesia and posture problems and may increase the risk for dementia in late stages. Among the many anticholinergics are trihexyphenidyl (Artane, Trihexy), benztropine (Cogentin), biperiden (Akineton), procyclidine (Kemadrin), and ethopropazine (Parisdol). Orphenadrine (Norflex) is a drug with anticholinergic properties, but is also a muscle relaxant and does not cause urinary retention.

Side effects of Anticholinergics. Anticholinergics commonly cause dryness of the mouth (which can actually be an advantage in some people who experience drooling). Other side effects are nausea, urinary retention, blurred vision, and constipation. These drugs can also increase heart rate and worsen constipation. Anticholinergics can sometimes cause significant mental problems, including memory loss, confusion, and even hallucinations. People with glaucoma should use these drugs cautiously.

Amantadine (Symadine, Symmetrel) stimulates the release of dopamine and may be used for patients with early mild symptoms. It has some benefit against muscle rigidity and slowness and may help some patients in advanced stages who are unresponsive to other drugs. It is less powerful than levodopa and may lose its effectiveness after 6 months. It may also reduce motor fluctuations brought on by levodopa, however, and these benefits appear to persist for at least a year. Large, well-conducted studies are still needed to determine its true benefits and safety.

Side Effects. Side effects are similar to those of anticholinergic drugs and also may include swollen ankles and mottled skin. It can also cause visual hallucinations. Overdose can cause serious and even life-threatening toxicity. Patients with Parkinson's should not withdraw from this drug abruptly. In rare instances, it can cause acute delirium or a life-threatening condition called neuroleptic malignant syndrome. Pregnant or nursing women should not use this drug.

Anticonvulsants. Zonisamide (Zonegran), a drug used to treat epilepsy, is showing promise in treating tremors, motor problems, and involuntary movements in patients with Parkinson’s disease.

Budipine and Other Glutamate Blockers. A number of experimental drugs are being investigated for Parkinson's disease because they block the actions of glutamate, an amino acid that is a particularly potent nerve cell killer. Some of these drugs block a receptor group to glutamate called N-methyl-D-aspartate (NMDA). Investigational NMDA antagonists include remacemide, memantine, riluzole, and budipine.

Stem Cell Transplantation. Scientists are investigating whether transplanting embryonic stem cells into the brain may help treat Parkinson’s disease. Researchers hope that the transplanted stem cells may be able to stimulate dopamine production. However, stem cell transplantation research is still in its very early stage. It will be many years before clinical trials will be conducted in humans.

Surgery

Surgical procedures are recommended for specific patients with advanced Parkinson’s disease who no longer respond to drug treatments. Surgical treatment cannot cure Parkinson's disease, but it may help control symptoms such as motor fluctuations and dyskinesia. Pallidotomy and thalamotomy are older procedures that destroy tissue in certain parts of the brain. Deep brain stimulation, the current standard surgical practice for Parkinson’s disease, has largely replaced the older operations.

In deep brain stimulation (DBS), also called neurostimulation, an electric pulse generator controls symptoms. The generator is similar to a heart pacemaker. It sends electrical pulses to specific regions of the brain. Candidates for surgery are generally patients who have responded well to levodopa drug treatment. Patients who have had PD for fewer than 16 years may experience greater benefit from DBS than patients who have had the disease longer.

Evidence indicates that DBS improves motor function and reduces dyskinesia best when the procedure targets the subthalamic nucleus (STN) of the brain. Many studies demonstrate the effectiveness of STN stimulation. Procedures that target the globus pallidus interna or ventral intermediate nucleus of the thalamus can also sometimes treat rigidity and tremors. However, there is not yet enough evidence to support stimulation of these parts of the brain.

The procedure is performed as follows:

The surgeon implants a tiny pulse generator near the collarbone, which is connected to four electrodes that have been implanted in the target area in the brain.
The generator delivers programmed pulses to this area, which the patient can turn on and off using a magnet held over the skin.
When on, the pulses suppress symptoms. Complications occur in 2 - 4% of operations. The most serious ones are bleeding in the brain and infection. Depression is common.

In a 2006 study of patients with advanced Parkinson’s disease and severe motor symptoms, patients who received DBS had better improvement in symptoms and quality of life than those who received only drug therapy. However, patients in the neurostimulation group had more serious side effects than those who were treated only with medications. Researchers are also studying whether DBS can benefit patients with earlier-stage Parkinson’s disease.

Pallidotomy and thalamotomy are surgical procedures that destroy brain tissue in regions of the brain associated with Parkinson’s symptoms such as dyskinesia, rigidity, and tremor. In these procedures, a surgeon drills a small hole in the patient’s skull and inserts an electrode to destroy brain tissue. Pallidotomy targets the global pallidus area. Thalamotomy targets the thalamus. Because these procedures permanently eliminate brain tissue, most experts now recommend deep brain stimulation instead of pallidotomy or thalamotomy.

Surgical complications may include behavioral or personality changes, trouble speaking and swallowing, facial paralysis, and vision problems. Weight gain after surgery is also common.

Scientists are investigating whether stem cells may eventually help treat Parkinson disease. Experimental surgery has shown promise using fetal brain cells rich in dopamine implanted in the substantia nigra area of the brain. Because the use of embryonic stem cells is controversial, researchers are studying alternative types of cells, including stem cells from adult brains and cells from human placentas or umbilical cords. Studies are also using gene therapies and other advanced treatments for transplanting dopamine-producing cells or nerve-protecting cells into the brain. All of this research is still in preliminary stages.

Lifestyle Changes

No special diets or natural foods have been shown to slow down the progression of Parkinson's disease, but there are some dietary recommendations.

Protein. High levels of proteins compete with levodopa for transport to the brain and reduce its effectiveness. Avoiding protein altogether is not the solution, since malnutrition can result. Most experts now recommend trying to maintain a carbohydrate-to-protein ratio of 7:1 throughout the day. This may be difficult to calculate and some doctors recommend simply keeping proteins to 12% of total daily calories.

As an aid in calculation, food labels indicate proteins in grams. One gram of protein equals four calories. Good control of protein intake may help minimize fluctuations and wearing-off and may allow some patients to reduce their daily levodopa dosage.

Fruits and Vegetables and Increasing Fiber. Eating whole grains, fresh fruits, and vegetables is the best approach for any healthy life. A diet rich in fruits and vegetables may help protect nerve cell function. Many of these foods are also often rich in fiber, which is particularly important for helping to prevent constipation.

Dietary fiber is the part of food that is not affected by the digestive process in the body. Only a small amount of fiber is metabolized in the stomach and intestine, the rest is passed through the gastrointestinal tract and makes up a part of the stool. There are two types of dietary fiber, soluble and insoluble. Soluble fiber retains water and turns to gel during digestion. It also slows digestion and nutrient absorption from the stomach and intestine. Soluble fiber is found in foods such as oat bran, barley, nuts, seeds, beans, lentils, peas, and some fruits and vegetables. Insoluble fiber appears to speed the passage of foods through the stomach and intestines and adds bulk to the stool. It is found in foods such as wheat bran, vegetables, and whole grains. Fiber is very important to a healthy diet and can be a helpful aid in weight management. One of the best sources of fiber comes from legumes, the group of food containing dried peas and beans.

People whose diets have been low in fiber should increase it gradually. It is best to obtain dietary fiber, soluble or insoluble, in the natural form of whole grains, nuts, legumes, fruits, and vegetables. If it proves difficult to do so, psyllium, a grain naturally found in India, is an excellent soluble fiber supplement (Metamucil, Fiberall, Perdiem Fiber). Fluids are particularly important in preventing constipation.

Fish Oil. Omega-3 fatty acids, which are found in oily fish, are proving to have powerful anti-inflammatory effects and may also be nerve protective.

Click the icon to see an image of foods that contain omega-3 fatty acids.

Dairy Products. A 2002 study reported a higher risk for Parkinson's disease in men (but not in women) who consumed high amounts of dairy products. This association was not linked to fats in dairy foods and high intake of calcium or protein from other sources did not increase the risk. A 2005 prospective study of men found that milk consumption in midlife was associated with increased risk of Parkinson’s disease. As with prior research, the researchers did not find that calcium itself carried a risk. They suggested that some unidentified neurotoxic contaminant in milk may be responsible.

Vitamins.

B Vitamins. Most B vitamins play important roles in the brain and central nervous system. Vitamin B6 (pyridoxine) theoretically has benefits for PD because it is necessary in the production and metabolism of dopamine. Folate deficiency may increase toxic effects against dopamine neural pathways, perhaps by increasing levels of homocysteine, an amino acid that may play a destructive role in many diseases, including heart and neurologic disorders. Some evidence suggests that L-dopa elevates homocysteine levels, so folate supplements may be particularly important for patients. Although the major food sources of B vitamins are meats and dairy products, which are high in protein, these vitamins are also found in whole grains and are added as supplements to commercial cereals.

Click the icon to see an image of the benefits of vitamin B6.

Click the icon to see an image of foods that contain vitamin B6.

Click the icon to see an image of foods that contain folate.

Vitamin E. Researchers have investigated antioxidant vitamins, especially vitamin E, for their effect on the brain. Some, but not all, studies have reported slower mental decline and lower risk for Parkinson's and Alzheimer's disease in people who ate large amounts of foods rich in vitamin E. Such foods include vegetable oils (particularly wheat germ oil), sweet potatoes, turnip greens, mangos, avocados, nuts, sunflower seeds, and soybeans. Vitamin E supplements, however, do not appear to be helpful for slowing disease progression or improving symptoms.

Both smoking and coffee drinking have been associated with lower risk for PD. Researchers are attempting to discover if these substances protect nerve cells. One interesting study suggested that the early disease process in PD produces changes in the dopamine pathway that actually protects an individual from caffeine and nicotine addiction, so that fewer patients have a history of smoking and caffeine. Research is needed to determine why these toxic substances protect against PD.

Smoking and Nicotine Replacement. Cigarette smokers appear to have a 40% lower risk for Parkinson's disease, indicating some protection by nicotine. This finding, of course, is no excuse to smoke, but such protection may help researchers develop new therapies. Studies on nicotine replacement, such as gum or patches, have been conflicting, however, with some short-term studies reporting no benefits. A 2002 study suggested that nicotine replacement may help smokers with early PD, but not nonsmokers.

Coffee Consumption. Studies have indicated that the risk for PD in coffee drinkers is about 30% lower than for non-coffee drinkers. In a 30-year study of Japanese-American men, coffee consumption was associated with a lower risk for Parkinson's disease, and the more coffee they drank, the lower their risk became. Coffee and tea can reduce fluids by increasing urination, however, and so may increase constipation in PD.

Regular use of ibuprofen may reduce the risk of Parkinson’s disease according to research presented at the 2005 annual meeting of the American Academy of Neurology. In this prospective study, people who took at least two ibuprofen tablets per week for at least 1 year lowered their risk of developing Parkinson’s by 35% compared to nonusers or irregular users. For those who took ibuprofen daily, the comparative risk was 38% lower. Other non-steroidal anti-inflammatory drugs (NSAIDS) did not appear to affect disease risk.

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.

The following dietary supplements are being studied for treatment of Parkinson's disease:

Creatine. Creatine is a nutritional supplement that is sometimes used to improve exercise performance. In 2007, the U.S. National Institutes of Health launched a large-scale clinical trial to study whether creatine can slow the progression of Parkinson’s disease. The trial will enroll patients who have been diagnosed with PD within the last 5 years and who have received levodopa therapy for no more than 2 years.

Coenzyme Q10 (Ubiquinone). Coenzyme Q10 (also called ubiquinone) is an antioxidant being studied for the treatment of Parkinson's disease. This enzyme is important for cellular energy, which may be impaired in PD. In one study, patients who took coenzyme Q10 had slower decline in daily activities and mental and motor skills compared to patients on placebo. However, a 2007 study found that small doses of coenzyme Q10 had no effect on improving Parkinson’s symptoms. Researchers are still investigating whether larger doses given over a long period of time may benefit patients.

Exercise early in adult life may help protect against later development of Parkinson’s disease. Exercise is also an important component of rehabilitation. Physical therapy is extremely important and usually includes active and passive exercise, gait training, practice in normal activities, and if needed, hot or cold treatments, water therapy, and electrical stimulation. Exercise is also essential for well-being and helps patients maintain productive years. To date, no specific approach has been proven to be better than others.

Exercise Programs. Exercise programs are defined as passive or active.

Passive exercise, mostly stretching and manipulation of muscles by a physical therapist, is aimed at preventing muscles from shortening. A passive exercise program that begins with slow and gentle exercises and becomes progressively more intense may improve mobility in patients with early and mid-stage Parkinson's disease.
Active exercises are used to help range-of-motion, coordination, and speed. Patients should continually make efforts to practice movement, even simple ones, such as marching in place, making circular arm movements, and raising the legs up and down while sitting. Patients who enjoy sports or the use of exercise equipment should continue with these activities even if their skills diminish, assuming there are no other medical conditions that would prevent participation.

Gait Training. Practicing new methods for standing, walking, and turning may help retain balance. The following tips may be helpful:

Take large steps when walking forward, raising the toes at the forward step, and hitting the ground with the heel.
Take small steps while turning.
When walking or turning, have the legs 12 - 15 inches apart to provide a wide base.
Do not wear rubber or crepe-soled shoes because they grip the floor and may cause the patient to fall forward.
Using devices that keep a rhythmic beat, such a metronome (a simple device used by musicians to keep time), may be very effective, possibly more than music itself, in helping patients to walk faster and take longer steps. One study found that setting a metronome rhythm to about 10% faster than the patient's fastest gait offers significant improvement over walking to no rhythm at all or to a rhythm that matches the gait.

Reducing Muscle Freezing. The patient should practice regular daily activities that simplify actions and reduce the incidence of muscle freezing. Most often, freezing occurs when a patient begins to move or is presented with an obstacle. The following tips may be helpful:

Rock from side to side.
If the legs feel frozen, lift the toes. This simple action may free spasm in some cases.
Hum marching tunes. In fact, music has been shown to help people move and to get out of bed in the morning. Some studies report that wearing a Walkman and turning music on in situations associated with freezing, such as crossing a street, is helpful.
Divide actions into separate events, which may prevent freezing that occurs from trying to coordinate too many physical operations at one time. For instance, when going through a doorway, approach the door, stop at the door, open it, stop, and then walk through the doorway.
A cane equipped with a laser pointer may be helpful, at least temporarily.
Simply being touched by another person can sometimes release the patient (although a patient with PD should never be pulled or pushed).

Sleep Deprivation Therapy. Sleep deprivation therapy may have a role in treating some cases of depression and some studies are finding some benefits on the depression, tremor, and rigidity experienced by patients. Scientists believe that sleep deprivation produces certain anticholinergic effects, which may improve both depression and Parkinson's symptoms.

Mental Tasks. Mental training may increase dopamine in the brain. Some studies indicate that being mentally fit may be as important for patients as being physically fit. Helpful approaches include:

Select and learn new hobbies that require finger and hand mobility, such as sewing, carpentry, fishing, or playing cards.
Practice deep breathing and relaxation exercises. These may help maintain proper speech control, control tremor, and reduce anxiety.
Both the patient and any caregivers should consider psychological therapy and support for depression and loss of motivation. If psychological therapy is too costly, inexpensive support programs and groups are widely available and can be invaluable for the patient and the family.

Speech Therapy. Speech therapy may help those who develop a monotone voice and lose volume, particularly in combination with medications. There are no well-conducted studies comparing specific speech therapies, but the Lee Silverman Voice Treatment (LSVT) appears to be an example of an effective technique. It has five major components:

Focus on the voice ("think loud/think shout")
High effort (pushes patients to overcome limitations)
Intensive treatment (16 sessions in 1 month)
Calibration (learning to know and accept the amount of effort needed to produce normal sound so it becomes automatic)
Quantification (continuous feedback to objectively document success)

LSVT may help swallowing as well as speech.

Equipment and Devices. A number of devices can be helpful for maintaining stability and preventing falls. The following are some examples:

Rails installed where the patient needs support in getting up or down, such as along the bed and in the bathroom.
Walkers with locking wheels. (Walkers do not appear to be helpful for freezing.)
Chairs with straight backs, firm seats, and arm rests.
Firm mattresses and satin sheets or less expensive sheets with high thread counts. (These are useful for helping patients slide out of bed.)

Resources

www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.aan.com -- American Academy of Neurology
www.apdaparkinson.org -- American Parkinson's Disease Association
www.pdf.org -- Parkinson's Disease Foundation
www.parkinson.org -- National Parkinson Foundation
www.michaeljfox.org -- Michael J. Fox Foundation for Parkinson's Research
www.wemove.org -- Worldwide Education and Awareness for Movement Disorders
www.parkinsonsaction.org -- Parkinson's Action Network

References

Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K, et al. A randomized trial of deep-brain stimulation for Parkinson's disease. N Engl J Med. 2006 Aug 31;355(9):896-908.

Murata M, Hasegawa K, Kanazawa I. Zonisamide improves motor function in Parkinson disease: a randomized, double-blind study. Neurology. 2007 Jan 2;68(1):45-50.

Schade R, Andersohn F, Suissa S, Haverkamp W, Garbe E. Dopamine agonists and the risk of cardiac-valve regurgitation. N Engl J Med. 2007 Jan 4;356(1):29-38.

Schupbach WM, Maltete D, Houeto JL, du Montcel ST, Mallet L, Welter ML, et al. Neurosurgery at an earlier stage of Parkinson disease: a randomized, controlled trial. Neurology. 2007 Jan 23;68(4):267-71. Epub 2006 Dec 6.

Storch A, Jost WH, Vieregge P, Spiegel J, Grelich W, Durner J, et al. Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q10 in Parkinson disease. Arch Neurol. 2007 July;64.

Voon V, Thomsen T, Miyasaki JM, de Souza M, Shafro A, Fox SH, et al. Factors associated with dopaminergic drug-related pathological gambling in Parkinson disease. Arch Neurol. 2007 Feb;64(2):212-6.

Watts RL, Jankovic J, Waters C, Rajput A, Boroojerdi B, Rao J. Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson disease. Neurology. 2007 Jan 23;68(4):272-6. Epub 2007 Jan 3.

Zanettini R, Antonini A, Gatto G, Gentile R, Tesei S, Pezzoli G. Valvular heart disease and the use of dopamine agonists for Parkinson's disease. N Engl J Med. 2007 Jan 4;356(1):39-46.

Review Date:
6/4/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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