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Acute Viral Encephalitis

Each year in the United States, approximately 7 patients are hospitalized for encephalitis per 100,000 population. The pathogen is unknown in approximately half these cases. Of the cases with a known cause, 20 to 50% are attributed to viruses. Herpes simplex virus (HSV) accounts for 50 to 75% of identified viral cases. Varicella zoster virus (VZV), enteroviruses, and arboviruses accounting for most of the remaining cases.

Viral encephalitis must be distinguished from autoimmune encephalitis and HSV encephalitis must be distinguished from other viral causes. Clinical features that favor HSV over other causes include older age, acute onset, fever, gastrointestinal symptoms, and a lower incidence of ataxia and rash. Compared to autoimmune encephalitis, patients with HSV encephalitis are more likely be male and less likely to have psychosis or rash. Most neurologic symptoms such as impaired consciousness, confusion, aphasia, hallucinations, and movement disorders, do not differ among the various types of encephalitis.

Overall, acute viral encephalitis has a poor outcome. Predictors of a poor outcome include the presence of an immunocompromised state, a Glasgow Coma Scale score of 8 or less (scale from 3 to 15, with lower scores indicating greater neurologic deficits), admission to an ICU, and an age of more than 65 years. In HSV encephalitis, predictors of a poor prognosis include coma, restricted diffusion on MRI, more than a 24-hour delay in the initiation of acyclovir therapy after admission, and older age. In West Nile virus disease, indicators of poor prognosis include older age, membership in certain ethnic groups, female gender, and coma.

Virologic testing for acute encephalitis includes testing of CSF by polymerase-chain-reaction (PCR) for DNA viruses and reverse-transcriptase PCR (RT-PCR) assays for RNA viruses. Initial testing in immunocompetent hosts should include PCR and RT­-PCR for HSV­1, HSV­2, VZV, and enteroviruses. Children younger than 3 years of age should also be tested for human parechoviruses. If these initial tests are negative additional testing can be undertaken, including CSF PCR tests for cytomegalovirus (CMV), human herpesviruses 6 and 7 (HHV­6 and HHV­7), Epstein–Barr virus (EBV), and HIV. These tier 2 tests are typically included in the initial evaluation of immunocompromised patients.

Serologic tests on CSF and serum are also important for the diagnostic workup of arboviruses. Orders for serologic tests of specific arboviruses should be based on geographic region, season, and exposure history. Serologic testing of CSF IgM may help diagnose encephalitis due to arboviruses, VZV, EBV, measles virus, mumps virus, rubella virus, rabies virus, or other causes.

Viral PCR or RT­PCR of specimens from the throat and nasopharynx may help establish a diagnosis of adenoviral infection, influenza, or measles; testing of saliva may help diagnose mumps or rabies; and testing of stool specimens may help diagnose enteroviral infections.

Diagnosis of rabies involves serologic testing of CSF and serum specimens, RT­PCR testing of CSF and salivary specimens, and electron­ microscopic and immunohistochemical examination of a full­ thickness, hair ­follicle– containing skin ­biopsy specimen from the back of the neck.

Food and Drug Administration has approved a multiplex PCR panel for detection of multiple pathogens associated with meningitis and encephalitis in CSF specimens, including seven viruses (HSV-1, HSV-2, VZV, enterovirus, cytomegalovirus, human herpesvirus 6, and human parechovirus).


Tyler, K. Acute Viral Encephalitis, New Engl J Med. 2018;379:557-66.

Tunkel AR, Glaser CA, Bloch KC, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2008;47:303-27.

Steiner I, Budka H, Chaudhuri A, et al. Viral meningoencephalitis: a review of diagnostic methods and guidelines for management. Eur J Neurol 2010;17(8):9991009.

Solomon T, Michael BD, Smith PE, et al. Management of suspected viral encephalitis in adults. Association of British Neurologists and British Infection Association National Guidelines. J Infect 2012; 64:347-73.

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