In general, the virus replicates outside the central nervous system (CNS) and gains entry either by hematogenous spread or by traveling along neural (rabies, HSV, VZV) and olfactory (HSV) pathways. The etiology of slow virus infections, such as those implicated in the measles-related subacute sclerosing panencephalitis (SSPE) and progressive multifocal leukoencephalopathy (PML), is poorly understood.

Once across the blood-brain barrier, the virus enters neural cells, with resultant disruption in cell functioning, perivascular congestion, hemorrhage, and inflammatory response. Although most histologic features are nonspecific, brain biopsies are the diagnostic criterion standard for rabies. In contrast to viruses that invade gray matter directly, acute disseminated encephalitis and postinfectious encephalomyelitis (PIE), secondary to measles (most common), Epstein-Barr virus (EBV), and CMV, are immune-mediated processes.

HSE, the most common cause of sporadic encephalitis in Western countries, is relatively rare; the overall incidence is 0.2 per 100,000 (neonatal HSV infection occurs in 2-3 per 10,000 live births). Arboviruses are the most common causes of episodic encephalitis with reported incidence similar to that of HSV. These statistics may be even more misleading because most people bitten by arbovirus-infected insects do not develop clinical disease, and only 10% develop overt encephalitis.

Among less common causes of viral encephalitis, varicella- zoster encephalitis has an incidence of 1 in 2000 infected persons. Measles produces 2 devastating forms of encephalitis: postinfectious, which occurs in about 1 in 1000 infected persons, and SSPE, occurring in about 1 in 100,000 infected patients. Typically, 0-3 unrelated cases of rabies encephalitis are identified yearly.

Arboviral JE and EEE are equally as catastrophic as untreated HSE, but other arboviruses are associated with a more benign clinical course. For example, St Louis encephalitis and WNE have a mortality rate of 2-20%, and death rates from WEE and LAC are less than 5%. The incidence of neurologic sequelae is around 25% but highly variable. The mortality rate associated with PIE secondary to measles approaches 40%, with a high rate of neurologic sequelae in survivors. SSPE is universally fatal, although the disease course may last anywhere from several weeks to 10 years. VZV encephalitis has a mortality rate of 15% in immunocompetent patients and virtually 100% in immunosuppressed patients. The mortality rate for EBV encephalitis is 8%, and the morbidity rate is 12%. Rabies encephalitis and acute disseminated encephalitis are virtually 100% fatal, though the medical literature includes reports of survivors.

Toxoplasma encephalopathy accounts for as many as 40% of patients who are HIV positive with neurologic disease who present with a subacute headache, encephalopathy, and, often, a focal neurological complaint. This may be the presenting symptom of immunosuppression/HIV infection.

CSF polymerase chain reaction (PCR): A PCR for DNA HSV is 100% specific and 75-98% sensitive within the first 25-45 hours. Types 1 and 2 cross-react, but no cross-reactivity with other herpes viruses occurs. Arguably, a series of quantitative PCRs documenting the decline of viral load with acyclovir treatment may clinch diagnosis without brain biopsy. HSV cultures: These are used to test lesions (also Tzanck smear), CSF (rarely positive), and blood. Viral serology: Complement fixation antibodies are useful in identifying arbovirus. Cross- reactivity exists among one subgroup of arboviruses, the flaviviruses (eg, St Louis encephalitis, JE, WNE), and with antibodies raised in persons inoculated with the yellow fever vaccine. Serologic tests for toxoplasmosis: These can be helpful in light of an abnormal CT scan, particularly in the case of single lesions. However, the overlap in titer between previously exposed but presently uninfected and reactivated groups may complicate interpretation.

CSF analysis is essential in the diagnosis and characterization of encephalitis. The most important diagnostic test in the ED to rule out bacterial meningitis is well-performed Gram staining and, if available, polymerase chain reaction of the CSF in patients with suspected HSV encephalitis. Identification of the organism, viral, bacterial, fungal, or parasite, will establish the etiology for the encephalitis.

Brain biopsy is the criterion standard because of its 96% sensitivity and 100% specificity for all organisms.

Empiric adult emergency treatment for HSV meningoencephalitis and VZV encephalitis is Acyclovir 10 mg/ kg (infuse over 1 h) q8h for 14-21 days. Acyclovir 10-15 mg/kg IV q8h is given for neonatal HSV; for HSV encephalitis in the pediatric population, Acyclovir 10 mg/kg IV q8h is given.

The following specialists should consult on patients with encephalitis: Neurosurgeon (if a brain biopsy is indicated), Neurologist, Neonatologist if indicated, Infectious Disease specialist.

WEE is associated with relatively low mortality and morbidity rates, although developmental delay, seizure disorder, and paralysis occur in children, and postencephalitic parkinsonism occurs in adults. CE usually is a milder disease, with most patients making a full recovery, though 25% of those with severe disease continue to have focal neurologic dysfunction. The mortality rate in treated HSE averages 20% and is correlated with mental status changes at time of first dose of acyclovir. Approximately 40% of survivors have minor-to-major learning disabilities, memory impairment, neuropsychiatric abnormalities, epilepsy, fine-motor-control deficits, and dysarthria.