Mortality and prognosis in herpes simplex Virus-1 encephalitis long-term follow up study.

BACKGROUND AND

OBJECTIVES

Herpes simplex virus-1 (HSV-1) encephalitis is the most prevalent form of viral encephalitis worldwide. Consensus statements on the rate of mortality are lacking, with most studies emphasizing short-term mortality risks . We aimed to describe variables effecting mortality for HSV-1 encephalitis in a long term well defined HSV cohorts.

METHODS

This is a retrospective study, encephalitis patients who were HSV-positive (HSV- 1,HSV-2 and VZV) in the cerebrospinal fluid (CSF) in 23 years' time frame were compared. Clinical, electrophysiological, imaging, and laboratory data were analyzed.

RESULTS

We identified 47 HSV-1, 8 HSV-2 and 216 with VZV patients with a molecular CSF PCR diagnosis. The median age at diagnosis was 63.3 (interquartile range(IQR) 50.42-72.52) for HSV-1, 46.79 (IQR 36.55-55.05) for HSV-2 and 60.33. (IQR 33.78-74.11) for VZV (p = 0.14). The mean follow up time was 6.25 ± 5.92 years for the group as whole. Among HSV-1 patients, during the follow-up period, 26 patients (55.31 %) died. Ten deaths occurred within the first year, with a median age of death of 70.6 [63.53-75.39]. Patients who died were older (70.6 [63.53-75.39 vs. 48.59 [37.88-61.71], p < 0.001), had a longer time to treatment initiation (4.01 ± 5.69 vs. 1.96 ± 3.58 days, p = 0.026), with cancer comorbidities more prevalent (42.3 % vs. 0 %, p < 0.001). Univariate analysis showed older age (HR 1.07, 95 % CI 1.03-1.10, p < 0.01), and cancer comorbidity (HR 5.55, 95 % CI 2.31-13.33, p < 0.001) were associated with significantly higher risk for mortality. Multivariate analysis confirmed that older age (HR 1.096, 95 % CI 1.04-1.15, p < 0.001), cancer comorbidity (HR 11.02, 95 % CI 2.76-43.9, p < 0.001) and lower lymphocyte count (HR 0.97, 95 % CI 0.95-0.99, p = 0.032) influenced mortality risk. The optimal cut-off age to predict mortality based on AUC-ROC curve was 63.29 (AUC = 0.83, sensitivity = 0.76, specificity = 0.80, PPV = 0.83, NNV = 0.73, p < 0.001). Patients above this age cutoff had a significantly greater cumulative incidence of mortality than did those aged 50-63 years (p < 0.01).

DISCUSSION: Mortality due to HSV-1 was high and highest in patients >63 years or immunocompromised patients. Favorable outcomes were associated with increased lymphocyte levels in CSF, and early antiviral treatment. These finding may help explain the wide discrepancies in reported mortality rates for HSV encephalitis patients.