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Viral encephalitis

Highlights

Causes

Encephalitis, an inflammation of the brain, is rare but can be caused by many different viruses. They include:

  • Herpes viruses, which include herpes simplex virus, Epstein-Barr virus, and varicella-zoster virus.
  • Arboviruses, which are transmitted by blood-sucking insects such as mosquitoes. In the U.S., mosquito-borne encephalitis types include West Nile encephalitis, Eastern equine encephalitis, Western equine encephalitis, St. Louis encephalitis, La Crosse encephalitis.
  • Enteroviruses, which are various viruses that enter the body through the gastrointestinal tract.
  • Rabies virus, which is transmitted from the saliva of an infected animal.
  • Viruses that cause childhood infections, such as rubella, measles, and mumps.

Symptoms

Encephalitis symptoms can appear within 2 days to 2 weeks of exposure to the virus. Many people who are infected do not develop any symptoms. In milder cases, symptoms may resemble the flu. In severe cases of encephalitis, symptoms may include:

  • Fever
  • Headache
  • Vomiting
  • Lethargy and reduced consciousness
  • Seizures
  • Memory loss
  • Stiff neck and back
  • Confusion
  • Speech, hearing, and vision problems
  • Muscle weakness
  • Partial paralysis
  • Loss of consciousness
  • Coma

Treatment

Because encephalitis can be dangerous, it needs to be diagnosed promptly. Patients are treated immediately, even before diagnostic tests identify the specific virus that caused the illness. If herpes is a possible cause, the standard treatment is the antiviral drug acyclovir. Once the cause has been determined, other drugs may be administered. Unfortunately, however, many types of encephalitis, such as the ones caused by West Nile virus and other arboviruses, do not respond to antiviral drugs.

Prevention

The best way to prevent becoming infected with a mosquito-borne virus is to avoid being bitten by a mosquito. Use insect repellant when you go outside, especially during the peak mosquito hours of dusk and dawn. Remove mosquito-breeding environments from your property.

Introduction

Encephalitis is a rare but potentially life-threatening inflammation of the brain that can occur in people of all ages. The most common cause of encephalitis is infection by a virus. In very rare cases, encephalitis can also be caused by bacterial infection, parasites, or complications from other infectious diseases. This report focuses on viral encephalitis.

Encephalitis: Viral Infection of the Brain

Many viruses can cause encephalitis. The West Nile virus, for example, has been responsible for well-publicized outbreaks in the U.S. Most people exposed to encephalitis-causing viruses have no symptoms. Others may experience a mild flu-like illness, but do not develop full-blown encephalitis.

In severe cases, the infection can have devastating effects, including:

  • Swelling of the brain (cerebral edema)
  • Bleeding within the brain (intercerebral hemorrhage)
  • Nerve damage (neuropathy)

The damage may cause long-term mental or physical problems, depending on the specific areas of the brain affected.

Other Viral Infections of the Central Nervous System. Viral infection and inflammation can affect multiple areas of the central nervous system, and is categorized by its location:

  • Meningitis: infection of the meninges (the membranes that surround the brain and spinal cord)
  • Meningoencephalitis: infection of both the brain and meninges
  • Encephalomyelitis: infection of the brain and spinal cord

Specific Viruses Implicated in Encephalitis

Encephalitis caused by viruses in the United States generally fall into the following groups:

  • Arboviruses are the primary cause of acute encephalitis (sudden-onset encephalitis caused by direct infection). Arboviruses, short for "arthropod-borne viruses," are spread by mosquitoes and ticks..
  • Herpes viruses are the other major cause of encephalitis in the U.S. This virus family includes herpes simplex, Epstein-Barr, cytomegalovirus, and varicella-zoster. Herpes simplex is the most important of these viruses because it can cause severe brain damage, but anti-viral therapy is very helpful if started promptly.
  • Enteroviruses, such as coxsackievirus, are viruses that enter the body through the gastrointestinal tract.
  • In rare cases, secondary encephalitis can develop following childhood viral diseases such as measles, mumps, and rubella.

[For more information, see the Causes section in this report.]

How Viruses Can Infect the Central Nervous System

Encephalitis can develop shortly after an initial viral infection, or it can develop when a virus that was lying dormant in the body suddenly reactivates. Viruses are simple, but powerful infectious organisms.

  • The virus infects a person (host) by penetrating a cell membrane and ejecting its genetic material (its DNA or RNA) into the cell.
  • The viral DNA or RNA takes control of important cell processes, telling the cell to make more viruses.
  • The cell ruptures, releasing new viral particles that infect other cells.

There are two ways that viruses can infect brain cells:

  • The virus silently invades the body. There are no initial symptoms. The virus is carried by the bloodstream to the nerve cells of the brain, where they gather and multiply. Viruses that enter the brain in this manner are often widely scattered throughout the brain. This is called diffuse encephalitis.
  • A virus first infects other tissue and then invades brain cells. Viruses that are transmitted from other tissues usually cause focal infection, meaning they produce extensive damage in only a small area of the brain.

The Central Nervous System

The brain and spinal cord comprise the central nervous system. The adult human brain weighs about 3 pounds (1.4 kilograms). There are two major parts of the brain:

  • The higher and larger forebrain (the cerebrum)
  • The lower and smaller brain stem

The Cerebrum

The cerebrum is the uppermost and largest part of the brain. It is the most highly developed section of the brain. There cerebrum has several components:

The Cerebral Cortex. The cortex is the outermost layer of the cerebrum. It is made of gray and white matter:

  • Gray matter is a thin sheet of nerve cells that cover the surface of the brain.
  • White matter is a bundle of insulated nerve fibers that underlies the cortex and makes up the core of the cerebral hemispheres.

The Hemispheres. The two hemispheres control higher brain functions, such as memory, learning, decision making, and processing input from the senses. They are each divided into four lobes, which regulate different brain functions:

  • Frontal lobe: This is the brain's "gatekeeper." It controls higher motor functions, including speech, and governs concentration, attention, inhibition, judgment, and personality traits.
  • Parietal lobe: Processes information from the senses and controls walking, posture, and head and eye movements.
  • Occipital lobe: Responsible for interpreting visual input from the eyes.
  • Temporal lobe: Responsible for interpreting auditory input from the ears. Also regulates how language is interpreted and retrieves information for memory storage.

The Basal Ganglia. The basal ganglia are clusters of gray matter within each of the lobes. They are important for coordinating voluntary muscle movement, balance, and posture.

The Limbic System. The limbic system is located deep in the cerebrum and controls interpretation of smell, instinctive behavior, emotions, and drives.

Brain Stem

The brain stem is responsible for all vital functions. It is divided into the following areas, which are responsible for specific functions:

  • Medulla: sleep, breathing, heartbeat, digestion, activation of higher forebrain functions
  • Pons: sleep, breathing, motor control, activation of higher forebrain functions
  • Cerebellum: movement coordination
  • Midbrain: walking, posture, head, eye movement
  • Hypothalamus: body temperature, appetite, sexual behavior, reproductive hormones
  • Thalamus: communication with higher forebrain

The Spinal Cord

The spinal cord extends out of the base of the skull through the vertebrae of the spinal column. It is continuous with the brain. Thirty-one pairs of nerves extend from the sides of the spinal cord to other parts of the body (the peripheral nervous system).

The Meninges and Cerebrospinal Fluid

The meninges are three membranes that enclose the brain and spinal cord. They contain cerebrospinal fluid, which protects the central nervous system from pressure and injury.

Causes

Herpes Viruses

The herpes virus group includes a number of common infections, including herpes simplex, varicella-zoster (the cause of chickenpox and shingles), cytomegalovirus, herpes virus 6, and Epstein-Barr (EB) virus (the cause of mononucleosis). Several thousand people are hospitalized each year from herpes-associated encephalitis. These viruses share certain features, including the capacity to cause an infection and then to go into hiding. They can lie dormant for periods of time as short as months or as long as a lifetime. In a few cases, when the viruses reactivate, they cause encephalitis. In fact, some evidence suggests that varicella-zoster, cytomegalovirus, and Epstein-Barr (EB) virus may be more common causes of encephalitis than previously thought. In most cases, however, encephalitis from these viruses occurs in people with impaired immune systems, such as people with HIV or organ transplant patients.

Herpes Simplex Virus. Herpes simplex virus (HSV) is the most common cause of encephalitis in developed countries and is responsible for about 10 - 20% of all adult cases of viral encephalitis. There are two distinct types of the herpes simplex virus: HSV-1 (commonly associated with oral herpes) and HSV-2 (which usually causes genital herpes, although HSV-1 can also cause this condition). HSV-2 causes 70 - 90% of encephalitis cases in newborn infants; the virus is transmitted through the mother's genital secretions. Although HSV-1 is the primary culprit in most adult cases of herpes encephalitis, HSV-2 may also cause a small number of these cases.

Herpes simplex encephalitis is the only effectively treatable form of encephalitis, but treatment (typically intravenous acyclovir) must be administered within the first few days of symptom onset. If left untreated, the mortality rate for patients with HSV-1 is about 70%; if treated, the mortality rate declines to 30%. The mortality rate for HSV-2 encephalitis in newborns ranges from 15 - 57%. [For more information, see In-Depth Report #52: Herpes simplex.]

Varicella-Zoster Virus. The varicella-zoster virus is responsible for both chickenpox (when the virus is called varicella) and shingles (when it is referred to as herpes zoster). Chickenpox is the initial infection, after which the virus remains dormant, often for a lifetime. If it erupts, usually years later, is does so in the form of shingles. Encephalitis caused by varicella can occur in both children and adults and be very serious. If it occurs as a result of herpes zoster in adults, the brain inflammation tends to be mild, except in immunocompromised patients. In such cases, symptoms can appear weeks to months after an attack of shingles and resemble those of a stroke. Fortunately, encephalitis is rare with both varicella and zoster. [For more information, see In-Depth Report #82: Shingles and chickenpox (varicella-zoster virus).]

Epstein-Barr Virus. Epstein-Barr virus is the cause of infectious mononucleosis, which is most common in children and young adults. Symptoms of the disease are severe fatigue, headache, sore throat, and fever. In 1% of cases, neurological complications occur about 1 - 3 weeks after the onset of the infection. If encephalitis develops, it is almost always mild with full recovery.

Cytomegalovirus Encephalitis. Cytomegalovirus is also very common and usually mild. In immunocompromised patients, such those with AIDS, it can be dangerous, with severe complications including encephalitis.

Arboviruses

Arboviruses, including the West Nile virus, are transmitted by blood-sucking insects such as mosquitoes and ticks. Most of the time, the viral infections initially develop in birds. Insects that feed on the infected blood from a diseased bird (which functions as the reservoir of infection) carry the virus, and transmit it when they bite a susceptible host (such as an animal or a human). Insects, such as mosquitoes, that play a role in the disease-transmission process are referred to as vectors.

Arboviruses multiply in blood-sucking vectors, nearly always mosquitoes. There is no evidence that these infections can be transmitted casually from one infected person or animal directly to another uninfected person without passing through a mosquito (or tick) first. (However, a small number of West Nile virus cases have occurred through blood transfusions, organ transplantation, and possibly breastfeeding.) Only about 10% of people who are infected by an arbovirus develop encephalitis and only about 1% of those infected have symptoms.

Arboviruses that cause encephalitis are primarily found in three virus families: Togaviridae, Bunyaviridae, and Flaviviridae. In the United States, the main mosquito-borne encephalitis strains are Eastern equine, Western equine, St. Louis, La Crosse, and West Nile. Equine encephalitis causes disease in both humans and, as its name implies, horses. Powassan encephalitis is a less common tick-borne flavivirus that occurs primarily in the northern United States. Japanese encephalitis is the most common form of viral encephalitis to occur outside of the United States. It is endemic in rural areas in east, south, and southwest Asia, especially China and Korea. Venezuelan equine encephalitis is found in South and Central America.

Different arboviruses cause different forms of encephalitis. Although the overall disease is the same, there are subtle differences in symptoms and the type of brain damage they produce.

Common Forms of Mosquito-Borne Arbovirus Encephalitis

Eastern Equine Encephalitis

Virus Family

Togaviridae (genus Alphavirus)

U.S. Geographic Areas

Atlantic and Gulf coasts, in New England, and around the Great Lakes. States most affected are Florida, Georgia, Massachusetts, and New Jersey.

Symptom Onset

Symptoms appear 4 - 10 days following infection and can range from mild flu-like symptoms to full-blown encephalitis.

Incidence and Mortality Rates

About 6 cases are reported each year. About a third of people who contract EEE die from it. Children are more likely to survive but also to suffer complications afterward.

Age Risk Groups

Adults over age 50 and children under age 15.

Western Equine Encephalitis

Virus Family

Togaviridae (genus Alphavirus)

U.S. Geographic Areas

Farming areas in western and central Plains and Rocky Mountain states west of the Mississippi.

Symptom Onset

5 - 10 days following infection.

Incidence and Mortality Rates

Very rare. Mortality rate is 3 - 4%; 30% of survivors have complications afterward. Most severe in children, especially those younger than 1 year. Infants may suffer permanent neurological damage.

Age Risk Groups

Infants younger than 12 months.

St. Louis Encephalitis

Virus Family

Flaviviridae (genus Flavivirus)

U.S. Geographic Areas

Takes its name from an epidemic in St. Louis, but has occurred throughout the U.S., especially central and southern states, as well as parts of Canada, Caribbean, and South America.

Symptom Onset

5 - 15 days following infection.

Incidence and Mortality Rates

Mortality rate range between 5 - 30%, with highest rates among elderly. About 5% of survivors suffer complications afterward.

Age Risk Groups

Elderly adults (over age 60) are at highest risk, and the disease is most severe in this age group. Younger people usually experience mild, flu-like symptoms.

La Crosse Encephalitis

Virus Family

Bunyaviridae (genus Bunyavirus)

U.S. Geographic Areas

Occurs most frequently in upper Midwestern, southeastern (Appalachia), and mid-Atlantic states. Most cases have occurred in Ohio and Wisconsin. Unlike other encephalitis viruses which originate in birds, La Crosse encephalitis is transmitted to mosquitoes from infected chipmunks and squirrels.

Symptom Onset

5 - 15 days following infection.

Incidence and Mortality Rates

Mortality rates are less than 1%. More common and severe in children under age 16.

Age Risk Groups

Children younger than 16 years.

West Nile Encephalitis

Virus Family

Flaviviridae (genus Flavivirus).

U.S. Geographic Areas

Cases have been reported throughout the mainland United States.

Symptom Onset

3 - 14 days following infection.

Incidence and Mortality Rates

In 2011, 690 cases of WNV were reported to the CDC, with 45 deaths. Of all the reported cases, 31% were due to West Nile fever and 69% to meningitis and encephalitis. However, most cases of West Nile virus do not produce symptoms, and are not reported, so these numbers imply a more worrisome picture than actually exists. In fact, fewer than 1% of people who are infected with WNV go on to develop neurological disease.

Age Risk Groups

Adults over age 50.

West Nile Virus (WNV). Until 1999, the West Nile virus was generally restricted to Africa, the Middle East, southwestern Asia, eastern Europe, and Australia. It emerged in the United States with the first outbreak in New York City in 1999. WNV is now found in birds and mosquitoes in every state except Alaska and Hawaii. Human cases of West Nile encephalitis have been reported throughout the continental United States. In recent years, the highest number of cases of WNV have been reported in Arizona, New Mexico, Nebraska, and Colorado

How WNV Is Transmitted. WNV, discovered in Uganda in 1937, circulates primarily between birds and mosquitoes and can be carried long distances by migrating birds. In a given geographic area, the appearance of the virus among birds and mosquitoes generally precedes infection in humans. WNV has infected over 110 species of birds. In addition to mosquito-to-human transmission, other causes of human infection have included blood transfusions and organ transplantation. The U.S. now uses screening tests to detect West Nile virus in donated blood and organs. There have also been cases of mother-to-child transmission during pregnancy. It is still not clear if WNV can be transmitted through breast milk.

Severity of WNV. About 80% of people infected with WNV will not have any symptoms. Twenty percent will develop West Nile fever (which includes fever, headache, and occasional skin rash). Less than 1% of infected people will develop neuroinvasive disease, the most severe form of WNV. It is still not clear if the physical and mental symptoms of West Nile virus persist long term.

Neuroinvasive disease affects the nervous system and includes encephalitis, meningitis, and poliomyelitis. People over age 50 and those with weakened immune systems are at the greatest risk for neuroinvasive disease. In older adults, neuroinvasive disease usually manifests as encephalitis. In children and younger adults, meningitis is more common. The fatality rate for those afflicted ranges from 3 - 15%. Neuroinvasive disease symptoms include high fever, headache, stiff neck, stupor, disorientation, coma, tremors, convulsions, muscle weakness, and paralysis. There are currently no vaccines to prevent WNV or specific antiviral drugs to treat it.

Tick-Borne Encephalitis Viruses

Tick-borne encephalitis (TBE) is commonly found in many countries throughout Europe, Asia, and the former Soviet Union, but it is reported only rarely in the U.S. Powassan encephalitis is the main tick-borne encephalitis found in the United States and Canada. The first human encephalitis fatality caused by deer tick virus, which is closely related to Powasson virus, was reported in 2009. Cases of tick-borne encephalitis have also been reported from Rocky Mountain spotted fever, but this is a bacterial (not viral) infection.

Enteroviruses

Enteroviruses include various viruses that enter the body through the gastrointestinal tract. They account for between 10 - 20% of viral encephalitis cases. The group A coxsackievirus has been detected in infants and children with encephalitis and is among the important viruses in the class. (However, enteroviruses are nearly as common as cold viruses and are rarely serious.) Enteroviruses can be spread through food or water contaminated by trace amounts of fecal material and through sneezing and coughing.

Other Viral Causes of Encephalitis

Rabies. The rabies virus is transmitted from the saliva of an infected animal. The encephalitis it causes is virtually always fatal but is very rare in the U.S. Only one or two cases are typically reported each year, often from contact with raccoons, bats, or other wild animals.

Encephalitis Associated with Childhood Diseases. Encephalitis occurs rarely after common childhood infections, such as rubella, measles, and mumps. Immunizations have almost completely eliminated these infections in developed countries. Measles encephalitis still sometimes occurs in immunocompromised children. Rarely, influenza has caused acute encephalitis, usually in children. (Flu vaccinations are important in preventing these events.) Although there used to be concern that diphtheria-pertussis-tetanus and measles-mumps-rubella vaccines could cause encephalitis, recent research indicates that these childhood vaccines are very safe and do not increase encephalitis risk.

Adenoviruses. Adenoviruses were first identified in 1953 from infected tonsils and adenoids. The viruses can cause respiratory or gastrointestinal infections that are usually mild. In rare cases, adenoviruses can cause encephalitis or meningoencephalitis, which can be fatal in 30% of patients. Symptoms include lethargy, confusion, coma, and symptoms of meningitis (stiff neck, headache, and vomiting).

Parasitic Causes of Encephalitis

Toxoplasmosis. Encephalitis from toxoplasmosis, which can be transmitted through a cat's feces or by eating contaminated food, rivals herpes as the most common infectious cause of encephalitis. However, this condition causes very mild symptoms in most people. People with HIV and impaired immune systems are at risk for more severe symptoms. In addition, in pregnant women toxoplasmosis can cause severe problems in the fetus’ central nervous system and eyes Toxoplasmosis can be treated with certain antibiotics.

Raccoon Roundworm. Raccoon roundworm (Baylisascaris procyonis) is a large parasitic worm that lives in the intestines of raccoons. Humans usually become infected by ingesting the worm's eggs through accidental contact with soil, wood chips, or tree bark contaminated with raccoon feces. The worm is harmless in raccoons but can produce severe central nervous system disease, including encephalitis, in people. Prompt treatment with larvae-killing drugs, such as albendazole, or anti-inflammatory drugs is not consistently effective, so it is extremely important to avoid infection. Raccoons should not be kept as pets. Eliminate access to food sources, like garbage cans and bird feeders, which will attract raccoons.

Other Parasitic Infections. Encephalitis may be caused by other parasitic infections, such as toxocariasis (from roundworms found in dogs and cats) or cysticercosi (from food or water contaminated with pork tapeworm eggs). These infections usually cause only chills, fever, and swelling of lymph nodes, though seizures and headaches can occur.

Bacterial and Fungal Organisms

In very rare circumstances, encephalitis may be caused by bacterial or fungal organisms.

Acute Disseminated Encephalomyelitis (ADEM)

Acute disseminated encephalomyelitis (ADEM) is a condition that can develop in patients recovering from a viral infection. (Less commonly, it is associated with childhood vaccinations for measles, mumps, and rubella.) Although it is not caused directly by a viral infection, ADEM has symptoms similar to viral encephalitis, such as fever, fatigue, nausea, and vomiting. In severe cases, ADEM can cause seizures and coma.

The inflammation associated with ADEM occurs predominantly in the white matter of the brain rather than the gray matter (the usual target of infectious encephalitis). The nerve cells do not die as they do in a viral infection. Rather, the nerve cell coating (called a myelin sheath) is partially destroyed in much the same way as it is in multiple sclerosis. Indeed, the two conditions may at first be difficult to distinguish and they can share common symptoms of myelin damage. These symptoms include vision problems and muscle paralysis.

Risk Factors

Encephalitis is a rare disease, extremely uncommon in the U.S. even for people in the risk groups discussed below. Many people fall into the following categories, but few of them will ever contract encephalitis.

Age

Encephalitis can occur at any age. Age-associated risks depend on the type of encephalitis virus. Newborn infants are particularly at risk for herpes virus. For arboviruses, infants are most vulnerable to Western equine encephalitis. Older children and teenagers are more susceptible to Eastern equine and La Crosse encephalitis. Older and elderly adults are at higher risk for Eastern equine, St. Louis, and West Nile encephalitis.

Immunocompromised Patients

Patients whose immune systems are compromised by conditions such as HIV-AIDS, cancer therapies, or organ transplantation are more susceptible than other individuals to any form of encephalitis. Of particular concern are varicella and cytomegalovirus encephalitis which tend to be more common and deadly in these patients than in the normal population.

Risk Factors for Herpes Viruses

Few people in the world have not been infected with at least one of the herpes viruses. Most of these viruses are easily transmitted in body fluids, including saliva. Chickenpox, which is caused by a type of herpes virus, can also be spread when someone coughs or sneezes, propelling infected droplets into the air. Infants can contract herpes simplex virus from an infected mother during delivery, which can have very serious consequences. [For more information, see In-Depth Reports #52: Herpes simplex and #82: Shingles and chickenpox (varicella-zoster virus).]

Risk Factors for Arboviruses

U.S. Geographic Regions. The primary risk factor for arbovirus encephalitis is living in areas of possible exposure to virus-carrying mosquitoes. Most viral outbreaks occur in rural or farming areas, but they can also occur in cities. While some forms of arbovirus encephalitis are limited to specific geographical regions, the West Nile virus has become endemic throughout the mainland United States. [See Common Forms of Mosquito-Borne Encephalitis table for more detailed regional information.]

Seasonal Risks. Transmission of arboviruses correlates with the mosquito season and is highest during the months of July through September (late summer through early fall). The ideal conditions for mosquito breeding are a wet spring followed by a hot, dry summer.

Prognosis

In most cases of arbovirus infection, symptoms are mild, last 3 - 5 days, and resolve without becoming serious. In fact, the infection is generally unrecognized as anything other than a mild flu.

Prognosis for Severe Encephalitis

Prognosis for severe encephalitis depends on many factors, including:

  • Age of the patient -- worse outcomes for infants under age 12 months and adults over age 55
  • Immune status
  • Preexisting neurological conditions
  • Virulence of the virus

Death from Suppression of Vital Functions

In severe cases of encephalitis, the swelling of the brain inside the skull places downward pressure on the brain stem. The brain stem controls vital functions, such as respiration and heartbeat, and if the pressure becomes too severe, these vital functions can cease and cause death.

Complications from Brain Damage

Survivors of encephalitis commonly experience neurologic consequences, which can be long-term and even permanent. The degree and type of brain damage can vary from mild-to-severe and from focal (in one part of the brain) to multifocal (several parts of the brain) to diffuse (throughout the brain).

While coma can occur in patients with severe encephalitis, it does not necessarily predict a fatal or severe outcome. Some patients experience no or mild-to-moderate complications after awakening from an encephalitis-associated coma.

The location and severity of the infection largely determines the pattern of brain damage and therefore its effects, which can be:

  • Physical (muscle control)
  • Behavioral and emotional (personality changes)
  • Cognitive (memory, speech)
  • Sensory (vision, hearing)

Symptoms

Symptoms of encephalitis usually appear within 2 days to 2 weeks of exposure to the virus. In milder cases, symptoms may resemble the flu. In severe cases of full-blown encephalitis, symptoms may include:

  • Behavioral and personality changes
  • Sensitivity to light
  • Fever
  • Headache
  • Vomiting
  • Lethargy and reduced consciousness
  • Memory loss
  • Stiff neck and back -- accompanied by fever and headache would indicate meningitis
  • Confusion
  • Speech, hearing, and vision problems
  • Muscle weakness
  • Seizures
  • Partial paralysis
  • Loss of consciousness
  • Coma

Patients experiencing these types of symptoms (especially if they may have recently been bitten by a mosquito or tick or if they have lesions on the lips or genitals) should immediately seek medical treatment.

Symptoms in Infants. Infants with herpes virus encephalitis may develop lesions in the mouth, in the eye, or on the skin 1 - 45 days after birth. Other symptoms include lethargy, seizures, and changes in temperature. The fontanels, the soft spots on their head where the skull has not yet closed, may bulge outward.

Diagnosis

Because the various types of encephalitis produce similar symptoms, doctors cannot rely on clinical features to differentiate among the many causes of brain inflammation. The primary objective in diagnosing viral encephalitis is to determine if it is caused by:

  • Herpes simplex or other conditions that can be treated with specific medications
  • Arboviruses or other viruses that can be managed only by targeting symptoms

Imaging Techniques

If the doctor suspects encephalitis, a scanning technique is often the first diagnostic step. Computerized tomography (CT) or magnetic resonance imaging (MRI) scans can show the extent of the inflammation in the brain and help differentiate encephalitis from other conditions. MRIs are recommended over CT scans because they can detect injuries in parts of the brain that suggest infection with herpes virus at the onset of the disease, while CT scans cannot.

Electroencephalogram (EEG), which records brain waves, may reveal abnormalities in the temporal lobe that are indicative of herpes simplex encephalitis.

Cerebrospinal Fluid Tests

When encephalitis is suspected, a sample of cerebrospinal fluid is taken using a lumbar puncture, which involves inserting a needle between two vertebrae in the patient's lower back. The sample is taken to count white blood cells and identify specific blood cell types, to measure proteins and blood sugar levels, and to determine spinal fluid pressure. Doctors use cerebrospinal fluid to test for herpes simplex virus, Epstein-Barr virus, varicella-zoster virus, enteroviruses, and to look for the presence of antibodies to the West Nile virus. While cerebrospinal fluid tests may help diagnose encephalitis, they cannot provide information on how severe the disease will be.

Blood Tests

Blood tests may be used to test for West Nile virus and other arbovirus infections.

Brain Biopsy

If necessary, tiny samples of brain tissue are surgically removed for examination and testing for the presence of the virus. Tissue is prepared using staining techniques and then viewed under an electron microscope. In a few cases, the viruses in brain cells are able to be cultured; that is, the viruses can actually be made to replicate in samples. A brain biopsy is the gold standard for diagnosing rabies.

Treatment

With the exception of herpes simplex and varicella-zoster encephalitis, the viral forms of encephalitis are not treatable. The primary objective is to diagnose the patient as soon as possible so they receive the right medicines to treat the symptoms. It is very important to lower fever and ease the pressure caused by swelling of the brain.

Patients with very severe encephalitis are at risk for body-wide (systemic) complications including shock, low oxygen, low blood pressure, and low sodium levels. Any potentially life-threatening complication should be addressed immediately with the appropriate treatments.

Treating Probable Causes of Encephalitis

Since it is difficult to determine the cause of encephalitis, and rapid treatment is essential, clinical guidelines recommend immediately administering intravenously the antiviral drug acyclovir without waiting to determine the cause of the illness.

Once the doctor receives results from diagnostic tests, drug treatment depends on the cause of the encephalitis. Antiviral drug treatments for specific causes of encephalitis include:

  • Herpes Simplex Virus. Acyclovir is recommended.
  • Varicella-Zoster Virus. Acyclovir is recommended. Ganciclovir or adjunctive corticosteroids may also be considered.
  • Cytomegalovirus. Combination of ganciclovir plus foscarnet.
  • Epstein-Barr Virus. Corticosteroids may be used, although risks may outweigh benefits. (Acyclovir is not recommended.)
  • Human Herpesvirus 6. Ganciclovir or foscarnet are recommended for immunocompromised patients.
  • Measles. Ribavirin may be considered.
  • ADEM. High-dose intravenous corticosteroids.
  • St. Louis Encephalitis. Interferon alfa-2a may be considered.

For bacterial meningitis, antibiotics (not antiviral drugs) are used.

Additional Treatments

Other encephalitis treatments are aimed at reducing symptoms.

  • Seizures may be prevented by using oral anticonvulsant drugs or intravenous lorazepam (Ativan).
  • Sedatives may be prescribed for irritability or restlessness.
  • Simple pain relievers may be used for fever and headache.
  • In patients who are otherwise stable, the only other treatment measures are to keep the head elevated and monitor the patient's status.

Investigational Treatments

No specific drugs have been effective for treating arboviruses, including West Nile virus, although a number of drugs used to treat other virus infections are being investigated. They include interferon alfa 2a (Roferon-A) and other interferons.

Vaccinations

Certain vaccinations can help prevent the diseases that can lead to encephalitis.

Measles

Measles used to be a very common childhood disease. In about 1 in 1,000 patients it can lead to encephalitis or death. The risk for these severe complications is highest in the very young and very old. Aggressive vaccination programs have reduced the incidence of measles in the U.S. to fewer than 100 cases a year. Rarely, patients who receive the live-measles vaccine develop encephalopathy (brain damage), but the risk is far lower than brain problems occurring from the disease itself.

Vaccine for Varicella Virus (Chickenpox and Shingles)

Herpes zoster, or shingles, is a reactivation of the varicella virus, which causes chickenpox. Children (and adults who do not have a history of infection and who lack evidence of immunity) should receive 2 doses of the chickenpox vaccine. A vaccine for shingles (Zostavax) is available for adults age 50 years and older. [For more information, see In-Depth Report #82: Shingles and Chickenpox.]

Vaccines for Arboviruses

A vaccine (Ixiaro) is currently available for adults traveling for a month or longer to Asian regions where Japanese encephalitis is endemic. (An older vaccine, JE-VAX, is no longer manufactured, but limited quantities are available for vaccinating children.) Countries and regions with high rates of Japanese encephalitis include Viet Nam, Cambodia, Myanmar (Burma), southern India, Pakistan, Nepal, Malaysia, Korea, northern Thailand, Malaysia, Sri Lanka, and the Philippines.

Another type of vaccine (FSME-IMMUN) is used to prevent tick-borne encephalitis (TBE) in travelers visiting regions where this type of encephalitis is prevalent. TBE is found mainly in Eastern and Central Europe. This vaccine is available in Canada and many European countries, but it is not yet approved in the United States.

Several types of vaccines are under investigation for West Nile virus, but it will be several years before these vaccines could become commercially available.

Rabies Vaccine and Immune Globulin

Anyone exposed to the secretions of an animal suspected of having rabies, should be evaluated for post-exposure rabies vaccine. Exposed individuals may also receive immune globulin unless they were previously vaccinated. The regimen is one shot of immune globulin and four shots of rabies vaccine given over a period of two weeks. The new types of rabies vaccines cause much less discomfort and many fewer adverse effects than the older ones. Side effects may include mild reactions such as pain, redness, or swelling at the injection site. Patients may experience pain at the injection site and low-grade fever following the immune globulin shot.

Prevention

The risk for mosquito-borne infections is highest between dusk and dawn, when mosquitoes feed. A good insect repellent is very helpful in reducing the risk for vector-borne disease. The most complete personal protection program for adults and most children is to apply the insect repellant DEET to the skin, and also permethrin to clothing and similar surfaces.

DEET and Other Insect Repellant Skin Products

DEET. Most insect repellents contain the chemical DEET (N,N-diethyl-meta-toluamide), which remains the gold standard of currently available mosquito and tick repellents. DEET has been used for more than 40 years and is safe for most children when used as directed. Comparison studies suggest that DEET preparations are the most effective insect repellents now available.

Concentrations range from 4% to almost 100%. The concentration determines the duration of protection. Most adults and children over 12 years old should use preparations containing a DEET concentration of 20 - 35% (such as Ultrathon), which provides complete protection for an average of 5 hours. (Higher DEET concentrations may be necessary for adults who are in high-risk regions for prolonged periods.)

DEET products should never be used on infants younger than 2 months. According to the Environmental Protection Agency (EPA), DEET products can safely be used on all children age 2 months and older. The EPA recommends that parents check insect repellant product labels for age restrictions. If there is no age restriction listed, the product is safe for any age. The American Academy of Pediatrics recommends that children use concentrations of 10% or less; 30% DEET is the maximum concentration that should be used for children. When deciding what concentration is most appropriate, parents should consider the amount of time that children will be spending outside, and the risk of mosquito bites and mosquito-borne disease.

When applying DEET, take the following precautions:

  • Do not use on the face, and apply only enough to cover exposed skin on other areas.
  • Do not over apply, and do not use under clothing.
  • Do not apply over any cuts, wounds, or irritated skin.
  • Only parents or an adult should apply repellent to a child. They should first put DEET on their own hands and then apply it to the child. They should avoid putting DEET not only near the child's eyes and mouth but also on the hands (since children frequently touch their faces).
  • Wash any treated skin after going back inside.
  • If using a spray, apply DEET outdoors -- never indoors. Spray repellents should not be applied directly on anyone's face.

Other Insect Repellent Products. The U.S. Centers for Disease Control (CDC) also recommends the mosquito repellents picaridin and oil of lemon eucalyptus.

Picaridin, also known as KBR 3023 or Bayrepel, is an ingredient that has been used for many years in repellents sold in Europe, Latin America, and Asia. A product containing 7% picaridin is now available in the United States. Picaridin can safely be applied to young children and is also safe for women who are pregnant or breastfeeding. According to the CDC, insect repellents containing DEET or picaridin work better than other products.

In scientific tests, oil of lemon eucalyptus, also known as PMD, worked as well as low concentrations of DEET. However, oil of lemon eucalyptus is not recommended for children under the age of 3 years.

Permethrin for Clothing and Surfaces

Permethrin is an insect repellent used as a spray for clothing and bed nets, which can repel insects for weeks when applied correctly. Electric vaporizing mats containing permethrin may be very helpful. A permethrin solution is also available for soaking items, but it should never be applied to the skin. Side effects from direct exposure may include mild burning, stinging, itching, and rash. In general, however, permethrin is very safe and its use may even reduce child mortality rates from malaria. People allergic to chrysanthemum flowers or who are allergic to head-lice scabicides should avoid using permethrin.

Controlling Mosquitoes around the House

Eliminate Sources of Standing Water. The best way for homeowners to reduce mosquito populations is to eliminate sources of standing water.

  • Look for any source of standing water, where mosquitoes can breed. For example, discard any rubbish with standing water, such as old tires, cans, and bottles. (Even bottle caps can breed mosquitoes.) Do not let water accumulate in outdoor flower pot basins or pet bowls. Turn over wading pools and wheelbarrows when not in use. Change bird bath water every 3 - 4 days. A product such as Mosquito Dunk can be used to prevent breeding in standing water.
  • Swimming pools and hot tubs should be clean and chlorinated or drained and covered if not in use.
  • Clean vegetation and debris from the edges of ponds.
  • Keep gutters clean and unclogged.

Mosquito Traps and Bug Zappers. Mosquito traps use various methods for repelling or attracting and trapping female mosquitoes, which are the primary transmitters of arboviruses. These methods include electricity or propane. However, there is little evidence to support their effectiveness.

Insect light traps (commonly called bug zappers), which attract and electrocute insects, may actually spread viruses and bacteria that are on the insects. They are also not very effective for killing female mosquitoes.

Citronella Candles. Burning citronella candles reduces the likelihood of bites. (Indeed, burning any candle helps to some extent, perhaps because the generation of carbon dioxide diverts mosquitoes toward the flame.)

Other Preventive Measures

Your home environment, personal hygiene, and what you wear can also help reduce your risk for mosquito bites:

  • Wear trousers and long-sleeved shirts, particularly at dusk.
  • Sleep only in screened areas.
  • Air-conditioning may reduce mosquito infiltration. Where air-conditioning is not available, fans may be helpful. Mosquitoes appear to be reluctant to fly in windy air.
  • Don't wear perfumes.
  • Cover up bare skin after dusk.
  • Wash your hair at least twice a week.

Community Mosquito Control Programs

Spraying. Public health measures are the most effective methods for controlling mosquitoes. Local communities that experience outbreaks of encephalitis or West Nile virus from mosquitoes often have public spraying programs that target mosquito larvae during breeding season as well as adult mosquitoes. The U.S. Environmental Protection Agency (EPA) approves the safety of the insecticides used. While these pesticides are generally considered safe for humans, people with asthma or other respiratory problems should avoid exposure by staying indoors while spraying takes place.

Report Dead Birds. Dead birds may be indicators that the West Nile virus has reached a specific region. Report any dead birds to your local public health authorities. You should never touch a dead bird with your bare hands.

Resources

References

Aksamit AJ Jr. Acute viral encephalitis. In: Goldman L, Schafer AI, eds. Cecil Medicine. 24th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 422.

Bleck TP. Arthropod-borne viruses affecting the central nervous system. In: Goldman L, Schafer AI, eds. Cecil Medicine. 24th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 391.

Centers for Disease Control and Prevention (CDC). West Nile virus disease and other arboviral diseases--United States, 2010. MMWR Morb Mortal Wkly Rep. 2011 Aug 5;60(30):1009-13.

Fischer M, Lindsey N, Staples JE, Hills S; Centers for Disease Control and Prevention (CDC). Japanese encephalitis vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010 Mar 12;59(RR-1):1-27.

Katz TM, Miller JH, Hebert AA. Insect repellents: historical perspectives and new developments. J Am Acad Dermatol. 2008 May;58(5):865-71. Epub 2008 Feb 13.

Lindquist L, Vapalahti O. Tick-borne encephalitis. Lancet. 2008 May 31;371(9627):1861-71.

Lindsey NP, Hayes EB, Staples JE, Fischer M. West Nile virus disease in children, United States, 1999-2007. Pediatrics. 2009 Jun;123(6):e1084-9.

Loeb M, Hanna S, Nicolle L, Eyles J, Elliott S, Rathbone M, et al. Prognosis after West Nile virus infection. Ann Intern Med. 2008 Aug 19;149(4):232-41.

Tavakoli NP, Wang H, Dupuis M, Hull R, Ebel GD, Gilmore EJ, et al. Fatal case of deer tick virus encephalitis. N Engl J Med. 2009 May 14;360(20):2099-107.

Tunkel AR, Glaser CA, Bloch KC, Sejvar JJ, Marra CM, Roos KL, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008 Aug 1;47(3):303-27.

Tyler KL. Emerging viral infections of the central nervous system: part 1. Arch Neurol. 2009 Aug;66(8):939-48.

Voelker R. Effects of West nile virus may persist. JAMA. 2008 May 14;299(18):2135-6.

Whitley RJ. Herpes simplex virus infections. In: Goldman L, Schafer AI, eds. Cecil Medicine. 24th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 382.


Review Date: 2/7/2012
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.
The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997- A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.
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