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Author: David R. Snydman
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1. Encephalitis

1.1. Background

  • Encephalitis indicates inflammation of the brain. Meningoencephalitis signifies inflammation of both the brain and meninges. Myelitis is inflammation of spinal cord.
  • Clinically the terms are useful to differentiate that area which is most affected by the pathologic process.
  • Any of the viruses associated with encephalitis can be among those which cause aseptic meningitis, however, there are a group of viruses (arboviruses) which cause epidemic encephalitis. In any epidemic, however, one should recognize that there will be a wide spectrum of disease ranging from asymptomatic infection to aseptic meningitis to frank encephalitis.

1.2. Epidemiology

  • Arboviruses tend to predominate and epidemic disease occurs almost yearly in the US. Certain arboviruses have a predilection for different geographic areas of the US depending on the climate, mosquito vector and the virus itself.
  • A comparison of the different arboviruses can be found in the accompanying table.
  • Herpes simplex virus is the most important cause of sporadic fatal encephalitis. Recognition is critical since this infection is a treatable form of viral encephalitis.
  • Many other viruses are capable of causing acute encephalitis including other members of the Herpes virus family, enteroviruses, mumps, LCM, adenovirus, and postvaccinal.

1.3. Clinical Manifestations

  • Meningoencephalitis usually begins with the acute onset of fever, headache, vomiting and stiff neck. Encephalitis is suggested by drowsiness, paralysis, coma, convulsions, ataxia, psychosis, and papilledema.
  • The electroencephalogram is usually diffusely abnormal with arboviral encephalitis. The CSF may vary between several hundred and several thousand white blood cells. Generally there is a lymphocyte predominance but Eastern Equine Encephalitis may have a polymorphonuclear predominance, especially in the early stages. The protein is usually elevated to 300-400 mg per dl. The glucose is usually normal (but may be depressed with H. simplex).
  • Herpes simplex encephalitis frequently has a temporal lobe focus on EEG, brain scan, CAT scan, MRI or arteriogram. The CSF frequently shows several thousand red blood cells in addition to a mildly elevated WBC. The glucose may be slightly depressed.
  • Because viral encephalitis involves the brain diffusely, such processes like secretion of inappropriate ADH may occur with resultant hyponatremia.

1.4. Diagnosis

  • Presence of HSV DNA in CSF detected by PCR is best means to make a diagnosis of HSV encephalitis. Arboviral infection detected by serum antibody of CSF, culture of CSF or serum antibody. Enteroviruses can be cultured from CSF, stool, and throat wash.

1.5. Differential Diagnosis

  • The differential diagnosis requires the exclusion of tumors, vascular malformations, a fungal or tuberculous process, toxoplasmosis, brain abscess, bacterial meningitis with an encephalitic component, Lyme disease, syphilis, or lead intoxication.

1.6. Prognosis

  • In contrast to aseptic meningitis the morbidity and mortality for encephalitis is considerable. The prognosis depends somewhat on the specific causative agent. For example, the overall mortality for arboviral encephalitis in the United States between 1955 and 1971 was 50% for Eastern Equine Encephalitis (EEE), 8% for St. Louis Encephalitis (SLE), 2.9% for Western Equine (WE) and 0.4% for California (CE). include source?
  • The mortality for untreated Herpes simplex encephalitis is 70%.With current therapy, acyclovir, the mortality can be reduced to about 15-20% but there may be considerable morbidity with long term neurologic sequelae, especially if the onset of treatment is delayed.
  • In children with WEE who were < 1 year of age at the onset of infection, 57% developed either mental retardation, paralysis, seizures, spasticity, speech difficulties, hearing defects.
  • The most treatable form of viral encephalitis is Herpes simplex.
  • There has been the introduction of a new course of viral encephalitis into US from Middle East-West Nile Encephalitis. It is a flavivious like St. Louis Encephalitis, Japanese Encephalitis and Dengue. Clinical manifestations similar to other viral encephalitides except profound weakness, lower motor neuron symptoms common. Most severe illness in elderly. Expanding pool of virus activity throughout US over 90 deaths last year.

2. Rabies

  • Rabies can present as a form of encephalitis.The virus is transmitted from animals to humans by salivary contamination of a bite or wound.Dogs, cats, bats and other animals may transmit the disease.
  • The virus is neurotropic. Enters skin, attacks peripheral nerves and spreads slowly to central nervous system. The incubation period can be weeks to months, and rarely even longer.
  • Diagnosis can be made by antibody determination, or immunofluorescence staining of impression smear of cornea, nerve biopsy or brain Bx. Pathognomonic Negri bodies may be present.
  • Clinical findings may be an encephalitis, personality change, agitation and eventually coma. It is uniformly fatal. Spasms on feeding or water exposure (hydrophobia) are classic findings, but are not always present and may be late findings.
  • ProphyClinical findings may be an encephalitis, personality change, agitation and eventually coma. It is uniformly fatal. Spasms on feeding or water exposure (hydrophobia) are classic findings, but are not always present and may be late findings.laxis of wound exposure with wound washing, rabies vaccine and human rabies immunoglobulin should be given when appropriate.

3. Chronic Encephalitis

  • Creutzfeldt-Jakob disease (CJD) is a spongiform encephalopathy related to scrapie of sheep, bovine spongiform encephalopathy (BSE) and kuru. The disease appears to be due to an infectious fibrillar protein called prion protein. This agent is transferable and resistant to chemical disinfection and heat disinfection.No nucleic acid present in infectious material. Infectivity associated with abnormal variant prion protein (PrPsc). Genes for normal prion protein (prp) found in all animals. Susceptibility to infection may have genetic basis. Presumed that infectious prpsc initiates irreversible conversion of host PRP to abnormal form.
  • Transmission is thought to be due to contaminated food. Nosocomial cases have occurred due to contaminated instruments, contaminated human growth hormone. The incubation period is years.
  • New variant CJD diagnosed in 1995, 10 years after BSE.
  • Disease is manifest by rapid onset of presenile dementia. The disease generally has its peak incidence in the 60’s. Clumsiness, ataxia, tremor are followed by intellectual and motoryoung adults.
  • There is no therapy. The only effective means of disinfection is autoclaving infected material (brain or CSF).

4. Post Vaccine States

  • Other form of chronic encephalitis may rarely occur in association with infection or vaccine administration. Examples include subacute sclerosing Panencephalitis (SSPE) secondary to measles immunization.
  • There are also rare chronic encephalitides associated with varicella-zoster infection, and rubella.

5. Differential Features of Common Encephalitis Producing Viruses Chart

Eastern Equine (EEE) Western Equine (WEE) St. Louis (SLE) California (CE) Herpes simplex
Geographic location Eastern Western South/Midwest North Central None
Vector Mosquito Mosquito Mosquito Mosquito None
Epidemics Yes Yes Yes Yes No
Summer Yes Yes Yes Yes No
Frequency 4 2 1 3 5
Age Distribution 20% <5 yo 30% <5 yo <6& child 90% <15 any age
% Males 55% 65% 50% 60% 50%
Mortality 50% 3% 7% 1% 15%

6. Ancillary Material

6.1. Readings

6.1.1. Required

  • Schaecter Textbook, Chapter 58, pages 535-548.

6.1.2. Suggested

  • Prusiner SB. Shattuck Lecture – Neurodegenerative diseases and prions. N Engl J Med 2001;344(20):1516.
  • Whitley RJ. Viral encephalitis. N Engl J Med 1990;323:242-250.