Encephalitis

What Is Encephalitis?

Viral Infections
Encephalitis is a general term for inflammation of the brain. It may be caused by a variety of different viral infections.
  • Encephalitis is defined as inflammation of the brain.
  • This definition means encephalitis is different from meningitis, which is defined as inflammation of the layers of tissue, or membranes, covering the brain.
  • Unfortunately, in some people, both of the diseases may coexist and lead to a more complex diagnosis and treatment plan; in addition, both conditions share many of the same symptoms so they may be difficult to distinguish.
  • There are many causes of encephalitis: viruses, bacteria, parasites, chemicals, and even autoimmune reactions. This article is designed to discuss general features of encephalitis; it is not designed to be all-inclusive as book chapters have been written on individual causes. The reader wanting more information than is present in this introduction is urged to click on the links provided and to check the references provided at the end of this article.
  • In clinical practice, most doctors consider encephalitis to be a viral illness.
  • Viruses such as those responsible for causing cold sores, mumps, measles, and chickenpox can also cause encephalitis; they will not be further discussed in this article because their major disease manifestations, symptoms, and complications are detailed in other articles.
  • Major causes of viral encephalitis are herpesviruses and arboviruses.
  • Arboviruses are spread by insects such as mosquitoes and ticks.
  • The equine (meaning horse), West Nile, Japanese, La Crosse, and St. Louis encephalitis viruses are all mosquito-borne arboviruses.
  • Although viruses are the most common source of infection, bacteria, fungi, parasites, chemicals, and autoimmune reactions (limbic encephalitis) can also be responsible for encephalitis. However, current data suggest that these are far less common than viral infections as causes of encephalitis.

Viral encephalitis resembles the flu in terms of its symptoms and usually lasts for two to three weeks. It can vary from mild to life-threatening and even cause death. Most people with a mild infection can recover fully. Those with more severe infections can recover although they may have damage to their nervous system. This damage can be permanent. Some other general features of viral encephalitis are as follows:

  • Age, season, geographic location, regional climate conditions, and the strength of the person's immune system play a role in the development of the disease and the severity of the illness.
  • Herpes simplex (the virus causing cold sores) remains the most common virus involved in encephalitis in the United States and throughout the world. These viruses are usually transmitted from person to person.
  • In the United States, there are five main encephalitis-causing viruses spread by mosquitoes: West Nile, Eastern equine encephalitis (EEE), Western equine encephalitis (WEE), La Crosse, and St. Louis encephalitis. Two types of Powassan viruses, an infrequent cause of encephalitis, are transmitted by at least two types of ticks.
  • Venezuelan equine encephalitis is found in South America. It can be a rare cause of encephalitis in the southwestern United States, particularly Texas. The infection is very mild, and nervous system damage is rare.
  • Japanese encephalitis virus is the most common arbovirus in the world (a virus transmitted by blood-sucking mosquitoes or ticks) and is responsible for 50,000 cases and 15,000 deaths per year worldwide. Most of China, Southeast Asia, and the Indian subcontinent are affected.

What Causes Viral Encephalitis?

  • Herpes simplex (HSV): This type of virus causes cold sores of the mouth and lesions of the genitals. HSV is transmitted directly through human contact. Newborns can also get the virus by passing through an infected birth canal. Once inside the body, the virus travels through nerve fibers and can cause an infection of the brain. The virus may also undergo a period of latency in which it is inactive. At a later time, emotional or physical stress can reactivate the virus to cause an infection of the brain. It causes the most subacute (between acute and chronic) and chronic (lasting three or more months) encephalitis infections in humans.
  • Arbovirus: Hosts are animals such as birds, pigs, chipmunks, and squirrels that carry the virus. Mosquitoes (known as vectors, or ways of transmitting the virus) feed on these animals and become infected. The virus grows and cycles between the hosts and the vectors. Humans become infected through mosquito bites. Once inside the body, the virus replicates and travels in the bloodstream. If there is a large enough amount of the virus, the brain can become infected. The majority of cases occur between June and September when the mosquitoes are most active. In warmer climates, the disease can occur year-round.
    • West Nile virus (WNV): This virus was first isolated from an adult woman with a fever in the West Nile District of Uganda in 1937. The nature of the virus was studied in Egypt in the 1950s. In 1957, as a result of an outbreak in Israel in the elderly, the WNV became recognized as a cause for severe inflammation of the spinal cord and brain in humans. In the early 1960s, it was first noted that horses were becoming ill in Egypt and France. This virus then emerged in North America in 1999, with encephalitis reported in humans and horses.
      • The virus cycles between the Culex mosquito and hosts such as birds, horses, cats, bats, chipmunks, skunks, squirrels, and domestic rabbits. The mosquito feeds on the infected hosts carry the virus in its salivary glands and then passes it on to humans or other animals during a blood meal. It usually takes three to 15 days from the time of infection to the onset of disease symptoms. In the U.S., crows became a major host, but the disease would kill the crows; as a result, the number of infections dropped dramatically as the crow population died off.
      • West Nile encephalitis is not transmitted from person to person (such as through touching or kissing or from a healthcare worker caring for a sick person) nor can it be passed from animal to human. Blood transfusions are the exception; the virus may be passed among people by blood transfusions if the donor is infected.
      • The chance that people will become severely ill from a mosquito bite is extremely small. According to the Centers for Disease Control and Prevention (CDC), even in areas where mosquitoes are reported to carry the virus, much fewer than 1% of them are infected. Furthermore, less than 1% of the people who get bitten and become infected will become severely ill. Therefore, the majority of cases are mild, and people can fully recover. For example, the CDC reported 690 people infected in 2011, with a total of 43 deaths.
      • Prognosis is usually guarded in the extremes of age (infants, young children, and the elderly). Death rates as a result of West Nile encephalitis range from 3%-15% and are highest among the elderly. At present, there is no documented evidence to suggest that a pregnancy is at risk due to WNV infection. It is assumed that if a person contracts WNV, he or she will develop lifelong natural immunity. However, it may wane in later years. Currently, there is no commercially available vaccine for humans.
      • A relative of West Nile virus, Powassan virus, was discovered in 1958, but its vector is the black-legged (deer) tick. It is very rare; only about 60 individuals have been diagnosed since 1958. There is no vaccine available. It has a 10% death rate.
  • La Crosse encephalitis: The first case occurred in La Crosse, Wisconsin, in 1963. Since then, the largest number of cases has been identified in woodland areas of the midwestern and mid-Atlantic United States. This virus is the most common cause of mosquito-borne encephalitis in children younger than 16 years of age. Each year, about 75 cases are reported to the Centers for Disease Control and Prevention (CDC). The virus cycles between the daytime-biting tree hole mosquito (Aedes triseriatus) and hosts such as chipmunks and squirrels. Some investigators consider the cause of California encephalitis to be the La Crosse virus. The La Crosse encephalitis virus can cause adverse effects on IQ and school performance. About 80-100 people are diagnosed each year in the U.S., and 1% of people with this infection may die.
  • St. Louis encephalitis: Since 1964, an average of about 102 people is reported infected per year. Outbreaks can occur throughout most of the United States, although large urban epidemics have occurred in the midwestern and southeastern regions. The last major epidemic of St. Louis encephalitis occurred in the Midwest from 1974-1977. There were 2,500 cases in 35 states reported to the CDC. Additionally, there were 20 reported cases in New Orleans in 1999. The virus cycles between birds and the Culex mosquitoes breeding in stagnant water. It grows in both the mosquito and the bird but does not make either one sick. Only the infected mosquito can transmit the disease to humans during the blood meal. The virus cannot be transmitted from person to person through kissing or touching nor can it be transmitted from the infected bird. The disease tends to affect mostly adults and is generally milder in children.

What Are Other Less Frequent Causes of Encephalitis?

  • Eastern equine encephalitis (EEE): According to the CDC, there have been confirmed cases in the United States of EEE since 1964 with a rate of about 0-21 diagnosed infections per year (average about six per year). This virus is found along the East and Gulf Coasts. The virus causes severe disease in horses, puppies, and birds such as pheasants, quails, and ostriches. In humans, flu-like symptoms develop four to 10 days after the bite of an infected mosquito. Usually, human illnesses are preceded by those in horses. EEE can cause death in 50%-75% of human infections; 90% of infected people have mild to severe impairments. Those who recover may suffer severe permanent brain damage such as mental retardation, seizures, paralysis, and behavior abnormalities.
  • Western equine encephalitis (WEE): This virus was isolated from the brain of a horse with encephalitis in California in 1930. The worst epidemic was in Canada and the western U.S. when over 300,000 horses and mules were diagnosed, along with over 3,300 humans in 1941. Since 1964, there have been at least 639 confirmed cases, but currently, only a few per year are reported. However, it remains a cause of encephalitis in the western part of the United States and Canada. In 1994, there were two confirmed and several suspected cases of WEE reported in Wyoming. In 1997, 35 strains of the WEE virus were isolated from mosquitoes collected in Scotts Bluff County, Nebraska. The WEE virus cycles between certain types of birds (small, mostly songbirds) and Culex tarsalis mosquitoes, a species associated with irrigated agriculture and stream drainage. The virus has also been found in several other mammals. Horses and humans become sick through bites by infected mosquitoes. Infants are particularly affected and can have permanent problems such as seizure disorders and developmental delay as a result of the infection. A vaccine is not available for humans. WEE is becoming more frequently encountered in the U.S.
  • Venezuelan equine encephalitis (VEE): This virus is found in Central and South America and is a rare cause of encephalitis in the southwestern part of the United States. It is an important cause of encephalitis in horses and humans in South America. From 1969-1971, an outbreak from South America to Texas killed over 200,000 horses. In 1995, there were an estimated 90,000 human infections with VEE in Columbia and Venezuela. The virus cycles between forest-dwelling rodents and mosquito vectors, especially the species Culex. VEE infection in humans is much less severe than that of WEE and EEE. While adults tend to develop a flu-like illness, children tend to develop overt encephalitis. Deaths are rare in humans but are common in horses. There is an effective vaccine for horses but none for humans.
  • Japanese encephalitis: This virus is responsible for 50,000 cases and 15,000 deaths per year. Most of China, Southeast Asia, and the Indian subcontinent are affected. The geographic distribution is expanding. Rarely, cases may appear in United States civilians and military personnel traveling to and living in Asia. Children and young adults are mostly affected. Older adults are affected when there are epidemics in new locations. The virus cycles between domestic pigs, wild birds, and Culex tritaeniorhynchus mosquitoes, which breed in rice fields. The disease is not transmitted through human contact, pigs, or birds. Only the mosquitoes can transmit the disease during feedings.
  • Zika virus: This virus is spread by the bite of an infected Aedes species mosquito; the virus can be passed from a pregnant woman to her fetus, and this has been associated with certain birth defects, including microcephaly, Guillain-Barré disease, and disseminated encephalomyelitis. A major outbreak of this disease began in 2015 and is ongoing in Brazil and has spread to other countries. Zika typically is spread via the mosquito vector, but transmission through sexual intercourse has also been documented.

The following is a short summary of the viruses that cause the majority of encephalitis infections, although they may also cause other diseases.

Disease Geographic Location Vector/ Hosts Comment
Herpes encephalitis United States/the world Human-to-human
contact
Prompt treatment with acyclovir increases survival to 90%
West Nile encephalitis Africa, West Asia, Middle East, United States Mosquito/mostly birds The majority are mild cases. Less than 1% of those infected will become severely ill. Full recovery is expected. A vaccine for humans is not commercially available.
Eastern equine
encephalitis
East Coast (from
Massachusetts to Florida),
Gulf Coast
Mosquito/birds Often occurs in horses. High mortality rate (50%-75%); frequent outcomes (seizures, slight paralysis), especially in children
Western equine
encephalitis
The Western United States and
Canada
Mosquito/birds Often occurs in horses.
Particularly affects infants
Venezuelan equine
encephalitis
Western Hemisphere Mosquito/rodents Rare in the United States; low mortality rate, rare after-effects
La Crosse encephalitis Throughout the United States, especially in midwestern & southeastern regions Mosquito/ chipmunks,
squirrels
The most common cause of
encephalitis in children younger than 16 years of age
St. Louis encephalitis Midwestern & mid-Atlantic
United States
Mosquito/birds Mostly affects adults
Japanese encephalitis Temperate Asia, southern and southeastern Asia Mosquito/birds and pigs Vaccine is available for ages 17 and older. See
Prevention section.
High morbidity/mortality rates
Zika virus South America, Asia, Pacific Islands, Central America Mosquitoes Birth defects including microcephaly, neurologic damage

A special cause of viral encephalitis is HIV. This virus is mainly known for its damage to the human immune system. However, as HIV disease progresses, some individuals develop encephalitis symptoms termed AIDS dementia complex. It results in cognitive disorders (There is memory loss, abstract thinking, and verbal fluency decline, and motor control may be markedly decreased.). Other causes of encephalitis are as follows but will not be further discussed in detail in this article; the reader is referred to the links provided:

  • Bacteria, such as N. meningitidis, and those that cause Lyme disease, syphilis, tuberculosis, and occasionally other bacteria such as Mycoplasma spp. have been implicated in a few individuals.
  • Fungi such as Candida, Mucormycosis, Cryptococcus, and others
  • Rabies virus
  • Parasites such as Toxoplasma (often seen in HIV-infected patients) or the parasite Naegleria
  • Allergies to vaccinations
  • Autoimmune diseases such as Rasmussen's encephalitis
  • Cancers involving the brain tissue
  • Prion caused encephalitis (rare) such as bovine spongiform encephalitis or mad cow disease
  • Myalgic encephalitis or chronic fatigue syndrome (no defined cause)
  • Chemical encephalitis such as that seen with alcohol (Wernicke-Korsakoff syndrome) due to a decline in liver functions and ultimately, affecting the brain tissue, or by drug use

In recent years, researchers have begun more intensive studies of some types of encephalitis. In 2012, the CDC began a multicenter study of epidemic myalgic encephalomyelitis (or chronic fatigue syndrome or CFS) that is ongoing to better understand this problem.

Another cause of encephalitis understudy is encephalitis believed to be caused by an autoantibody attack on subunits of brain N-methyl-d-aspartate (NMDA) glutamate receptors. The autoantibodies are termed anti-NMDA receptor antibodies, and the disease is termed NMDA receptor encephalitis, first identified in 2007. The disease is found mainly in young women (over 80%) and has been associated with ovarian teratomas (germ cell tumors). Some investigators think it may have been seen previously as an outbreak of encephalitis of unknown cause termed (epidemic) encephalitis lethargica that occurred worldwide between 1918 and 1928. Recent research suggests that the anti-NMDA receptor symptoms (seizures, unresponsiveness, motor-control problems, and others) caused by this autoimmune disease can be treated with immunotherapy to reduce or halt symptoms in some patients. Some individuals believe this disease is related to autism but currently, no convincing evidence has shown such a relationship.

Is Encephalitis Contagious?

The answer to this question depends upon the underlying cause of encephalitis. For example, some herpes viruses are contagious from person to person and can cause encephalitis. In this case, encephalitis is considered to be contagious. Viruses that are transmitted through the bite of infected insects are not considered contagious from person to person. Other causes of encephalitis such as autoimmune problems or chemical encephalitis are not contagious.

What Is the Incubation Period and Contagious Period for Encephalitis?

The contagious period and incubation period for encephalitis depend on the underlying cause of encephalitis. For example, some herpesviruses have an incubation period of about three to seven days on average but may range from about one to three weeks. The contagious period for some viruses may include the incubation period and the time it takes for the lesions (blisters, for example, in shingles) to crust over. Consequently, the contagious period and incubation period for encephalitis depend upon the cause of encephalitis being contagious; noncontagious encephalitis has no contagious or incubation period.

What Are Encephalitis Symptoms and Signs?

The signs and symptoms of encephalitis are the same for adults and children. Infants may have poor feeding, irritability, vomiting, bulging fontanel, and body stiffness; such symptoms in an infant always constitute a medical emergency.

  • Signs and symptoms may last for two to three weeks, are flu-like, and can include one or more of the following which in some individuals may become progressively worse and continue over time:
    • Fever
    • Fatigue, muscle weakness, rhythmic muscle contractions, muscle pain
    • Sore throat
    • Stiff neck and back
    • Loss of appetite
    • Vomiting and nausea
    • Headache
    • Confusion
    • Irritability
    • Unsteady gait, weakness
    • Problems with coordination
    • Drowsiness
    • Visual sensitivity to light
  • More severe cases may involve these signs and symptoms:
    • Seizures
    • Muscle weakness
    • Paralysis
    • Memory loss
    • Sudden impaired judgment
    • Delirium and/or hallucinations
    • Disorientation
    • Poor responsiveness or altered level of consciousness

What Specialists Treat Encephalitis?

There are many causes (see causes section) of encephalitis. What type of specialists may be consulted depends upon the underlying cause of the disease. In general, primary-care physicians, pediatricians, emergency medicine specialists, infectious-disease specialists, toxicologists, critical-care specialists, neurologists, and possibly others may be consulted to help diagnose and treat encephalitis.

When Should Someone Seek Medical Care for Encephalitis?

Call the doctor for immediate advice if an infant, child, or adult develops acute signs and symptoms of encephalitis if they have any of these associated conditions:

  • Sores around the lips or genitals through contact with another person
  • Having been in wooded or forest areas and suspect mosquito bites
  • Visiting an area where these viral (or other) diseases are common, especially outside the United States
  • Having been bitten by a tick

If signs and symptoms of encephalitis develop and the doctor is not available, go immediately to a hospital's emergency department for further evaluation. Do not hesitate or decide on your own that you or your child simply have the flu. Symptoms indicating severe illness require emergency treatment.

How Do Doctors Diagnose Encephalitis?

The doctor will often question a patient about their travel history. Geographic location and seasonal occurrence can help identify the specific cause of encephalitis. The doctor will often do a physical exam that includes looking for insect bites and will probably complete a neurologic evaluation. The physician often will order some blood tests, including a complete blood count (CBC). Depending on the patient's unique situation, the doctor may perform one or more of the following tests:

  • An imaging study of the brain such as a CT scan or magnetic resonance imagining (MRI) is often done. MRI is the procedure of choice if herpes encephalitis is suspected.
  • A study called polymerase chain reaction (PCR) to detect the genetic material of the virus has greatly improved the diagnosis of herpes encephalitis. Variations of this test are used by the CDC and some state agencies to identify the various other virus types that may cause encephalitis.
  • A reading of the electrical activity of the brain with an EEG can detect irregularities. Herpes encephalitis produces a characteristic EEG pattern.
  • A lumbar puncture, also known as a spinal tap, may be necessary to isolate and identify the virus. During this procedure, the doctor applies local numbing medication and then inserts a needle into the lower back to collect fluid from the space around the spinal column for analysis.
  • The virus may also be isolated from tissue or blood.
  • Urine or serum toxicology screening tests may also be done.
  • Brain biopsy is an option although it is rarely done and usually only if the other tests do not give an answer.

What Is the Medical Treatment for Encephalitis?

Encephalitis is usually a viral illness, which means that antibiotics are not used to treat viral infections. However, some antiviral drugs have been used to treat HSV infections, and some doctors may attempt to use antiviral drugs on other acute viral infections. No antiviral drugs to date are used to treat arboviral infections.

As mentioned previously, there are other nonviral causes (see above) of encephalitis, so the treatment for a given case depends on the doctor's working diagnosis. If the encephalitis is due to non-viral causes, then other treatments, specific to the cause, are warranted. Many clinicians consult an infectious disease, immunology, or cancer expert to help manage the various types of treatments. With the exception of herpes encephalitis, the mainstay of treatment is symptom relief. People with viral encephalitis are kept hydrated with IV fluids while monitoring for brain swelling. Anticonvulsants like lorazepam (Ativan) can be given for seizure control. Steroids have not been established as being effective although they may still be used in some cases. Diuretics may be used to lower intracranial pressure in individuals who have encephalitis and increased intracranial pressure.

  • Herpes encephalitis can cause rapid death if not diagnosed and treated promptly. Therefore, medication is usually started when the doctor suspects herpes to be the diagnosis without waiting for the confirmatory results. The recommended treatment is acyclovir (Zovirax) given by IV for two to three weeks. Acyclovir-resistant herpes encephalitis can be treated with foscarnet (Foscavir). Liver and kidney functions are monitored through the course of medication.
  • Currently, the use of antiviral drugs in the treatment of other types of viral encephalitis is being studied.

Self-Care at Home for Encephalitis

Because encephalitis can cause death, seek treatment from a primary care doctor or a hospital's emergency department if the patient seems very ill.

  • Any home treatment or remedy to relieve the flu-like symptoms should be carried out according to the doctor's advice and recommendation after diagnosis.
  • If the symptoms become more severe, transport the person to an appropriate emergency facility (for example, an infant or child should go to an emergency center that has a pediatric facility as part of the hospital).

Follow-up for Encephalitis

It is important to follow up with the doctor after the initial treatment because certain nervous system problems (complications) can develop after what appears to be a successful initial treatment. Relapse can occur with herpes encephalitis.

Complications of encephalitis may include the following:

  • Seizures
  • Coma
  • Increased intracranial pressure

Is It Possible to Prevent Encephalitis?

There are no commercially available human vaccines for most arboviral diseases in the U.S. There is a Japanese encephalitis vaccine available in the U.S., but it is for ages 17 and above and not widely available. Equine (horse) vaccines are available for EEE, WEE, and Venezuelan equine encephalitis (VEE), but none of these are available for humans. A vaccine against human encephalitis is available in Europe against viruses that are transmitted by tick vectors (tick-borne encephalitis or TBE or TBEV), but this vaccine is not available in the U.S. currently (2016). Some of the causes of encephalitis are contagious (for example, herpes, HIV, and most bacterial causes) while others require vectors like mosquitoes or ticks (West Nile virus, WEE, VEE, Zika, and others) and are not spread from person to person.

The following measures are suggestions for the prevention of encephalitis that is transmitted by vectors (mosquitoes, ticks):

  • Wear long pants and long-sleeved shirts to avoid ticks and mosquitoes when in forests or grassy areas.
  • Use insect repellant in exposed areas of the body.
  • Avoid spending a long time outdoors during dusk when insects tend to bite.
  • A Caesarian section (C-section) can be performed if the mother has active herpes lesions of the genital tract to protect the newborn.
  • Vaccinate children against viruses that can cause encephalitis (measles, mumps).
  • Japanese encephalitis can be prevented with three doses of the vaccine. Take precautions when traveling to areas where this strain is common (available mainly for ages 17 and older).
    • According to the U.S. Centers for Disease Control and Prevention, the vaccine is not recommended for all travelers to Asia. It should be offered to people spending a month or longer in areas where the disease-causing mosquitoes are known to be present and during the transmission season. However, travelers spending fewer than 30 days should receive the vaccine if the area is experiencing an epidemic outbreak.
    • The benefit of the vaccine should be weighed against the side effects and the risk of developing the disease by getting the shot. The risk of developing a serious allergic reaction such as hives is low.
    • Special consideration should be given to the elderly and pregnant women. The elderly have a higher chance of developing symptoms with infection. The Japanese encephalitis virus can infect the fetus and cause death. Therefore, these two groups should be cautious when traveling abroad.

Prevention methods of human-to-human transfer of specific viral, bacterial, and other rare causes of encephalitis are detailed in individual articles available in links to the specific diseases (for example, herpes, HIV, and specific bacterial types).

What Is the Prognosis of Encephalitis?

The outcome of the disease varies and depends on factors such as initial cause, age, the severity of the case, and the strength of the immune system. For example, people who are HIV positive, have cancer, or who have other illnesses have a weaker immune system and are less able to withstand another disease. These patients have a wide range of outcomes that range from good to poor. In general, those people with mild cases and otherwise relatively good health usually will recover without any problems. Poorer outcomes can be summarized as follows:

  • The death rate for certain patients with viral encephalitis can be high.
  • The St. Louis encephalitis virus can cause death in up to 30% of the cases.
  • Japanese encephalitis can cause death rates that range from 0.3% to 60% of the people infected, usually within the first week of illness.
  • In untreated cases of herpes encephalitis, 50%-75% of people die within 18 months. Treatment with acyclovir (Zovirax) can increase survival up to 90%.
  • Patients with AIDS or chemical (alcohol) encephalitis often have only a fair to poor outcome.

The cause of encephalitis has an important bearing on outcomes; as medicine advances, the prognosis may improve for some causes. Readers are encouraged to research other specific articles and links to get more information and details about potential treatments that improve outcomes for each cause of encephalitis.

References
Ayoade, Folusakin O. "California Encephalitis." Medscape.com. July 1, 2016. <http://emedicine.medscape.com/article/234159-overview>.

Howes, David S. "Encephalitis Clinical Presentation." Medscape.com. Apr. 3, 2016. <http://emedicine.medscape.com/article/791896-clinical#b3>.

United States. National Institute of Neurological Disorders and Stroke. "NINDS Rasmussen's Encephalitis Information Page." Dec. 19, 2011. <http://www.ninds.nih.gov/disorders/rasmussen/rasmussen.htm>.