Management of herpes simplex encephalitis (HSE) has been considerably improved by the availability of acyclovir therapy and rapid polymerase chain reaction (PCR)-based diagnostic assays. Prognostic factors for this rare affliction are, however, misestimated. We conducted a large retrospective multicenter study that included 93 adult patients in whom HSE was diagnosed by PCR from 1991 through 1998 and who were treated with intravenous acyclovir. Among the 85 patients assessed at 6 months, 30 (35%) had a poor outcome, which led to death in 13 patients (15%) and severe disability in 17 (20%). The outcome was favorable for 55 patients (65%). A multivariate analysis identified 2 factors that were found to be independently associated with poor outcome: a Simplified Acute Physiology Score II >/=27 at admission and a delay of >2 days between admission to the hospital and initiation of acyclovir therapy. Early administration of antiviral therapy is the only parameter that can be modified to improve the prognosis of patients with HSE.

The main predictor of outcomes in herpes simplex virus (HSV) encephalitis (HSE) is the delay between hospital admission and initiation of acyclovir. In this study, factors associated with late initiation of acyclovir were identified. The study included adults from northern France whose cerebrospinal fluid (CSF) was positive for HSV by PCR. Late initiation of acyclovir was defined as a delay of >1 day from hospital admission. In total, 184 patients were retrospectively enrolled from January 1991 to December 2002. The median age was 60 years (range: 17-91), and 102 (55.4%) were male. Acyclovir was initiated >1 day after hospital admission in 68 patients (37.0%). According to multivariate analysis, independent risk factors for late initiation of acyclovir were severe underlying disease (Knaus score >or=C) (OR 4.1; 95% CI 1.5-11.7); alcohol abuse (OR 3.4; 95% CI 1.3-8.9); and a delay of >1 day from admission to first brain imaging (OR 8.4; 95% CI 3.9-18.0). In addition, univariate analysis suggested an association between a finding of <10 leukocytes/mm(3) in CSF at admission (OR 2.5; 95% CI 0.7-5.8). These characteristics were found in 26 (14.1%), 23 (12.5%), 66 (35.9%) and 27 (14.7%) patients, respectively. One risk factor was identified in 109 (59.2%) patients, two in 29 (15.8%), and three in six (3.3%). Patients with HSE often present with severe underlying disease, chronic alcohol abuse, or atypical CSF findings, and such factors should not be allowed to delay diagnosis and administration of acyclovir.

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