Herpes Simplex Encephalitis in Sweden, 1990-2001: Incidence, Morbidity, and Mortality

BACKGROUND: Herpes simplex encephalitis (HSE) is a devastating disease. METHODS: In Sweden, a nationwide retrospective study of the incidence, morbidity, and mortality associated with HSE during the 12-year period 1990-2001 was conducted. The national inpatient register data were used, and diagnostic data from the virus laboratories were validated. RESULTS: In the study period, 638 patients hospitalized in Sweden received a primary diagnosis of HSE. Of these, 236 patients had a confirmed infection of the central nervous system due to herpes simplex virus type 1. This corresponds to an incidence of confirmed HSE due to herpes simplex virus type 1 of 2.2 cases per million population per year. Of the survivors, 87% were readmitted to the hospital. The most frequent diagnosis at readmission was epilepsy, which was found in 49 patients (21% of the 236 total patients; 24% of 203 survivors), with a median onset 9.3 months after the diagnosis of HSE. This corresponds to a 60- to 90-fold increase in risk, compared with that for the general population. Neuropsychiatric sequelae were evident in 45 (22%) of 203 surviving patients. The incidence of venous thromboembolism, including pulmonary embolism, was 5-14 times higher than that in the general population. Among patients with HSE due to herpes simplex virus type 1, the 1-year mortality was 14% (33 of 236 patients died), which was 8 times higher than expected. CONCLUSIONS: This is, to our knowledge, the first study to report long-term, nationwide follow-up data for patients with virologically confirmed HSE. There is considerable morbidity after HSE, with epilepsy being the most common diagnosis. This demonstrates the need for expanding our knowledge of the pathogenesis of HSE to direct more effective antiviral and antiinflammatory treatments.