Encephalitis: Overview

Encephalitis is the medical term for inflammation of the brain, a potentially life-threatening condition that can occur in people of all ages but which is fortunately extremely rare.

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Incidence; Causes and Development; Contributing Risk Factors

Encephalitis can occur at any age, but the highest risk is in children under four years of age, with a peak from three to six months, and among adults, especially those over age 60.  Both eastern and western equine encephalitis disproportionately affect infants.  The eastern variant also tends to affect children and the elderly.  La Crosse encephalitis nearly always infects children (not infants or adults).  St. Louis encephalitis usually occurs in adults over 40 years old.

Encephalitis is usually caused by infection with one of many different viruses; the West Nile virus has been responsible for the high-profile outbreak in the Northeast U.S.

Viral Causes of Encephalitis

Viral encephalitis infections that are caused by arboviruses are transmitted by mosquitoes or ticks (the 'vectors').  An important subgroup of such vector-transmitted diseases consists of flaviviruses, which include West Nile, Japanese encephalitis virus, and St. Louis encephalitis virus.

Arboviruses multiply in blood-sucking vectors, nearly always mosquitoes.  There is no evidence that these infections can be transmitted from one infected person or animal directly to another uninfected person without passing through a mosquito (or tick) first.  Only about 10% of people who are infected by an arbovirus develop encephalitis, and symptoms arise in only about 1% of those infected: arboviruses are responsible for only about 150 to 3,000 cases of encephalitis each year.

Some tick-borne encephalitis cases have been reported, but only rarely in the US.  The most notable is Rocky Mountain spotted fever.  Ticks can also carry related viruses that cause brain inflammation, particularly one known as Russian spring-summer encephalitis.  This encephalitis is most common in China, Korea, and the eastern areas of Russia.  Only a very few viral tick-borne cases of encephalitis have been reported in the US.

Enteroviruses account for 10-20% of viral encephalitis cases.  For example, the group A coxackievirus has been detected in infants and children with encephalitis and is among the important viruses in this class.  It should be noted that 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.

The herpes virus group includes a number of common infections, including herpes simplex, varicella-zoster (the cause of chicken pox and shingles), cytomegalovirus, herpesvirus 6, and Epstein-Barr (EB) virus (the cause of mononucleosis).  These viruses share certain features, including the capacity to cause an infection and then to go into hiding.  They can remain 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 that previously thought.

Herpes simplex virus (HSV) is the most common cause of so-called sporadic encephalitis (encephalitis that crops up in individuals rather than in insect-borne outbreaks) in developed countries and is responsible for about 10% to 20% of all cases of viral encephalitis.  Note that the annual incidence of encephalitis caused by HSV is only two cases per million people.  There are two distinct types of the herpes simplex virus: HSV-1 (which tends to cause oral herpes) and HSV-2 (which usually causes genital herpes).  HSV-1 is the culprit in most adult cases of herpes encephalitis, while both types can cause encephalitis in infants.  Herpes simplex encephalitis is the only effectively treatable form of encephalitis.

The varicella-zoster virus is responsible for both chicken pox (when the virus is called varicella) and shingles (when it is referred to as herpes zoster ).  Chicken pox 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, the brain inflammation tends to be mild except in immunocompromised patients.  Fortunately, encephalitis is rare with both varicella and zoster.

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 one to three weeks after the onset of the infection.  If encephalitis develops, it is almost always mild with full recovery.

Other viral causes of encephalitis include:

  • Rabies. Transmitted from the saliva of an infected animal, the encephalitis caused by the rabies virus is virtually always fatal but is very rare in the US.  Only one or two cases are typically reported each year, often from contact with bats.
  • Encephalitis Associated with Childhood Diseases. Encephalitis occurs rarely after common childhood infections, such as rubella, measles, and mumps.  Immunizations have almost wiped out these complications in developed countries.  Measles encephalitis still sometimes occurs in immunocompromised children.  Rarely, influenza has caused acute encephalitis, usually in children.
  • Adenoviruses. 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 cases.  Symptoms include lethargy, confusion, coma, and symptoms of meningitis (stiff neck, headache, and vomiting).

Parasitic Causes of Encephalitis

Raccoon roundworm (Baylisascaris procyonis) is a large parasitic worm that lives in the intestines of raccoons.  In one Wisconsin study, half the raccoons tested were infected.  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 humans.  At least 12 severe cases have been reported in the US since 1981, most in children younger than six years of age (who are at higher risk because of their tendency to put their fingers or other objects into their mouths).  Prompt treatment with larvae-killing drugs such as albendazole or anti-inflammatory agents is not consistently effective, so it is extremely important to avoid infection.

Encephalitis may be caused by other parasitic infections, such as toxoplasmosis, which is transmitted in a cat's fecal matter; toxocariasis, from roundworms found in dogs and cats; or cysticercosis, 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), also called noninfectious encephalitis, constitutes one-third of all known cases of encephalitis.  It is not caused by a virus, although it most often develops in patients two to three weeks after recovery from a viral illness.  (It does not affect children under two.)  Damage to nerve cells in such cases is caused not by the viral infection, however, but most likely by an autoimmune reaction, in which the body's immune system attacks its own brain tissue.

ADEM has been reported as a rare complication of childhood illness, including chicken pox, mumps, or measles.  Vaccination reduces these risks to nearly insignificant levels.  It is a complication of the rabies vaccine in one out of 30,000 cases.  Varicella (chicken pox) and nonspecific respiratory infections are now the most common causes of ADEM, but such cases are also extremely rare.

The inflammation 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.  Recurrences may occur several months to years after the initial episode.

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

Risk Factors for Arboviruses. US 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 areas, but they can also occur in cities.  People all over the country can be exposed to western equine encephalitis, although it is more likely to occur in the west.  In addition, people in the Midwest are at risk for La Crosse and St. Louis encephalitis.  Mosquitoes infected with the West Nile virus have now been found up and down the eastern seaboard and the Midwest and are spreading.

Seasonal Risks.  The chances for transmission of arboviruses are highest during the months of July through September.  The ideal conditions for the mosquitoes that harbor the virus for St. Louis encephalitis are a relatively mild winter, wet spring, and hot, dry summer, although arboviruses such as West Nile are cropping up early in the east even after the drought-stricken spring of 2002.  Mosquitoes can carry the virus over a winter and transmit it the next year.

Risk Factors for Herpes Viruses. It is a very rare individual anywhere in the world who has not been infected with at least one of the herpes viruses.  Many of these viruses are easily transmitted in saliva or in droplets after people exhale or sneeze.  One exception is herpes simplex virus 2 (HSV-2), which is sexually transmitted or is passed from an infected mother to her newborn infant during delivery.

Signs and Symptoms

Symptoms of encephalitis usually appear within 4-14 days of exposure to the arbovirus.  The symptoms and severity of the condition depend on the age of the patient at time of the infection, the type of virus, and the part or parts of the brain affected.  Early symptoms of arbovirus encephalitis usually last 3-5 days, usually resolve without becoming serious, and are similar to those of a flu and usually include fever, headache, nausea and vomiting, muscle aches, and lethargy.

Because encephalitis involves one or more parts of the brain, however, those with the condition may develop personality changes, confusion, or other disturbing mental symptoms as well as poor muscle control and sensory impairment – features that distinguish it from an ordinary flu.

People with St. Louis encephalitis sometimes have problems with urination; West Nile virus may produce a non-itchy rash on the chest, back, and arms (lasting about a week), loss of muscle tone, and weakness.

The standard symptoms of severe (full-blown) arbovirus encephalitis include:

  • Behavioral and personality changes
  • Sensitivity to light
  • Vomiting
  • Lethargy and reduced consciousness
  • Seizures (uncommon with West Nile Virus)
  • Memory loss
  • Stiff neck and back
  • Confusion
  • Coma.

In addition to the standard symptoms of encephalitis noted above, motor disorders are likely in arbovirus-related encephalitis.  They include severe general weakness, an inability to coordinate voluntary muscle movements (ataxia), tremor, partial paralysis, difficulty in hearing, seeing, or speaking (Broca's aphasia), or difficulty in swallowing (dysphagia).

Symptoms of Herpes Simplex Encephalitis
Early symptoms of encephalitis in herpes simplex patients include fever and headache.  In cases caused by the varicella virus, Epstein-Barr, or cytomegalovirus, early symptoms usually include a rash and swollen glands.  Adult patients with herpesvirus encephalitis usually have no rash.  Symptoms of herpesvirus encephalitis may evolve slowly, but most often they appear abruptly.  The standard symptoms include:

  • Stiff neck
  • Seizures
  • Partial paralysis
  • Stupor
  • Coma
  • Odd mental states
  • Smell and taste disturbances
  • Loss of speech or comprehension
  • Memory loss
  • Emotional volatility
  • Bizarre or psychotic behavior
  • Confusion.

Because of the local nature of the infection, herpes simplex may produce symptoms that differ from other forms of viral encephalitis, including loss of feeling or paralysis on one side of the body, or other specific symptoms that are isolated to one side.  About 50% of patients have such symptoms.  In severe cases without treatment, respiratory arrest can occur within the first 24 to 72 hours.

Infants with herpesvirus encephalitis may develop lesions in the mouth, in the eye, or on the skin within one to 45 days.  The infant may be irritable, have changes in attention span, and experience seizures.  Their fontanelles, the soft spots on their head where the skull has not yet closed, may bulge outward.

Rabies Symptoms
Symptoms usually develop one to three months after exposure to the virus, depending on the location of the wound.  Pain or numbness occurs in the wound.  Initial symptoms are fever, apathy, and headache followed by local twitching and convulsions.  The patient often hallucinates and exhibits strange behaviors.  Spasms occur in the throat, causing profuse salivation.  The patient refuses to drink anything.  Eventually, the patient becomes paralyzed and goes into a coma.

Diagnosis and Tests

In many cases, the symptoms of encephalitis are too similar to aid the physician in differentiating among the many causes of brain inflammation.  The primary objective in diagnosing viral encephalitis is to determine if it is caused by:

  • Arboviruses or other viral agents that can only be managed by relieving symptoms.
  • Herpes simplex or other conditions that are potentially treatable.

In most of the relatively common US arbovirus infections, including St. Louis encephalitis and the West Nile virus, fewer than 1% of infections cause any noticeable symptoms.  Symptoms that occur are usually minor and flu-like.

Treatment and Prevention

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 in order to administer any medications that might treat the symptoms.  It is imperative to lower fever and ease the pressure caused by swelling of the brain.

Patients with very severe encephalitis are at risk for systemic (body wide) 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.

Since it is difficult to determine the cause of encephalitis, and since rapid treatment is essential, it is common to medicate the patient for the causes that respond to medication without waiting to determine the cause of the illness:

  • Some experts advise immediately administering intravenous acyclovir, the standard treatment for herpes simplex encephalitis, to all patients whose symptoms indicate encephalitis.
  • Corticosteroids, which reduce inflammation, may also be administered immediately.
  • Antibiotics, which attack bacteria but not viruses, are used in case the cause of the symptoms is bacterial meningitis.

For any form of encephalitis, supportive treatments are aimed at reducing symptoms:

  • Seizures may be prevented using fosphenytoin (Cerebyx).  If they develop, they can be treated with 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.

Antiviral Agents:

  • Acyclovir.  Intravenous acyclovir is the treatment of choice for encephalitis caused by herpes simplex virus or varicella-zoster virus.  It should be started immediately and administered for at least 10 days.  Although at this time treatment is nearly always administered in the hospital, some centers are finding that some patients can be safely treated with intravenous medications at home after the first few days, although close monitoring by a health professional is essential.  Some experts advocate use of acyclovir in any patient with herpesvirus who has fever and any other early symptoms of encephalitis, since the drug is relatively safe and delay may have significantly negative effects on outcome.
  • Other Antiviral Agents.  Other antiviral agents have been investigated, but to date acyclovir has proven superior.
  • Foscarnet (Foscavir) is another powerful antiviral agent known as a pyrophosphate analogue, which may be useful for herpes simplex viral strains that have become resistant to acyclovir.
  • Foscarnet or ganciclovir, another antiviral drug, may have some benefits for patients with encephalitis from cytomegalovirus.
  • Ribavirin (Virazole) is under evaluation for La Crosse virus.

Relapse Rate.  Of concern is a relapse rate of about 25% in patients who have been successfully treated for herpes encephalitis.  It is not clear whether all such relapses are a reactivation of the herpes virus or whether they are caused by a different virus.

Erythropoietin. If the body requires an increase in oxygen, the kidney produces more of the hormone erythropoietin (EPO), which acts in the bone marrow to increase the production of red blood cells.  A genetically engineered version of the hormone, called recombinant erythropoietin epoetin alfa (Epogen, Procrit, AraNESP) is used in many disorders requiring an increase in red blood cells.  Some evidence suggests that it also helps protect the brain.  Experimental work suggests it may be helpful for ADEM patients.  It is very safe and warrants investigation in other forms of encephalitis as well.

ADEM is usually treated with high-dose intravenous methylprednisolone, a corticosteroid.  This agent is a powerful anti-inflammatory drug.  Intravenous immunoglobulin (IVIG) is also showing promise in certain patients.  Experimental work suggests that the hormone epoetin may help these patients.

Prognosis; Complications

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

Prognosis for severe encephalitis depends on a host of factors such as the following:

  • The age of the patient.  (Worse outcomes can be anticipated for infants less than one year of age and adults over 55 years of age.)
  • Immune status
  • Preexisting neurological conditions
  • Virulence of the virus.

Coma is a common symptom in patients with severe encephalitis but does not necessarily predict a fatal or severe outcome.  In one study of eastern equine encephalitis, some survivors averaged five days in a coma and had no or only mild to moderate complications afterward.  One patient was in a coma for nine days and had only mild complications afterward.

Most people exposed to these viruses have no symptoms – or only a mild flu-like illness – and do not go on to develop full-blown encephalitis.  In severe cases, however, the infection can have devastating effects, including the following:

  • Swelling of the brain (medically referred to as cerebral edema)
  • Bleeding within the brain (intercerebral hemorrhage)
  • Nerve damage.

The damage it does may cause long-term cognitive or physical problems, depending on the specific locations in the brain affected.

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.

Brain damage can cause complications in survivors.  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).  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).

Signs, symptoms & indicators of Encephalitis:

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Conditions that suggest Encephalitis:


Hearing Loss

Encephalitis can cause sensorineural hearing loss.

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