Viral Encephalitis: A Deadly Differential Diagnosis

Abstract & Commentary

Source: Whitley RJ, Gnann JW. Lancet. 2002;359:507-512.

Whitley and Gnann reviewed the recent literature on viral encephalitis and present an up-to-date summary of the pathogenesis, clinical syndromes, diagnosis, and treatment of several familiar and unfamiliar viral encephalitides.

Viral encephalitis is an unusual but often deadly manifestation of human infection. For some viruses such as mumps, central nervous system (CNS) infection is a common but usually benign part of the syndrome. For others such as Japanese encephalitis, neurological disease is the most prominent clinical feature of systemic infection. In the case of rabies, infection inevitably and exclusively results in CNS disease. In contrast, herpes simplex virus (HSV) is a common pathogen but only rarely causes encephalitis.

In a nonepidemic setting, HSV is the most common viral encephalitis. Because specific antiviral therapy is available for HSV encephalitis, confirmation of the diagnosis is urgent. Fortunately, the commonly used neurodiagnostic tests including CT, MRI, and EEG can provide useful information in the assessment of encephalopathic patients. Evaluation of the CSF is essential in patients with viral encephalitis and usually reveals a predominantly mononuclear pleocytosis and increased levels of protein. The use of PCR applied to the CSF to detect viral nucleic acids has become the diagnostic method of choice for HSV and other viral infections of the CNS.

Worldwide, viruses transmitted to humans by the bites of arthropods, mosquitoes, and ticks are especially causes of encephalitis. In the United States, most cases of arthropod-borne encephalitis have been attributed to LaCrosse virus and St. Louis encephalitis (see Table).

Selected Mosquito-Borne Arbovirus Encephalitides

Virus Geographical Distribution
in United States
Age-Group Affected Mortality
Western Equine West, Midwest Infants, Adults
(> 50 years)
Moderate in infants
Low in adults
Eastern Equine East, South Children and Adults > 30%
St. Louis Central, West, South Adults (> 50 years) 20%
LaCrosse Central, East Children 10-15%
West Nile East Coast Adults Low

Table adapted from: Whitley RJ, Gnann JW. Lancet. 2002;359:507-512.

Beginning in August 1999, an epidemic of encephalitis due to West Nile virus occurred in and around New York City. West Nile virus encephalitis is a disease encountered in Africa, The Middle East, and Eastern Europe but had not been identified previously in the Western Hemisphere. The recurrence of additional cases of West Nile virus in North America during subsequent summers indicates that the virus has established an enzootic cycle of transmission involving migratory birds and mosquitoes. New outbreaks are likely throughout the United States.


This useful review highlights the pathogenesis and clinical features of the familiar causes of viral encephalitis. In addition, Whitley and Gnann warn of high probability of future epidemics of encephalitis caused by previously unknown pathogens or as new manifestations of an increased virulence of known agents. Clinicians need to be aware of the broad spectrum of viral pathogens when assessing a patient presenting with possible acute viral encephalitis. —John J. Caronna

Dr. Caronna, Vice-Chairman, Department of Neurology, Cornell University Medical Center, Professor of Clinical Neurology, New York Hospital, is Assistant Editor of Neurology Alert.