HSVE accounts for 20 % of encephalitis cases and its annual incidence is 1/250,000-1/500,000 in industrialized nations and is presumed to be the same across the globe.

HSVE usually peaks in childhood (between 3 months and 6 years during primary infection with HSV-1) and in older people (bimodal distribution). The manifestations of HSVE include low-grade pyrexia accompanied by severe headache, nausea, vomiting, and lethargy, followed by neurological features, which may include cognitive dysfunction (confusion, acute memory disturbances and disorientation), behavioral changes (irritability, hallucinations, psychosis, personality changes, agitation), focal neurological abnormalities (such as focal weakness, anomia, aphasia, dysphasia,), hemiparesis and seizures. There may be marked temporal lobe edema and occasionally brainstem herniation. 20 % of HSVE cases may present a relatively mild or atypical disease.

Etiology

HSV-1 causes 90 % of cases of HSVE with 10 % of cases caused by HSV-2; the latter is a common cause in neonates (during vaginal delivery) and the immunosuppressed. HSVE results from primary infection in 1/3 of cases and reactivation in 2/3. Mutations in genes such as TLR3 (4q35) and TRAF3 (14q32.32) have been observed suggesting an influence of genetic factors, presumably by an impaired type I and type III IFN production in response to HSV-1. In 7 % of patients with HSVE, antibodies against NMDAR (N-methyl-D-aspartate receptor), may be detected. Post-HSVE, abnormal movements or relapse of symptoms may be related to these antibodies.

Prognosis

If untreated, mortality rates are 70 % that can be reduced to 28% following treatment. However morbidity remains high and survivors often have residual deficit such as chorea or epilepsy. A delay of 48 hours or more in starting acyclovir is associated with poor outcome.