Herpes Simplex Virus Encephalitis With Initial Negative Polymerase Chain Reaction in the Cerebrospinal Fluid: Prevalence, Associated Factors, and Clinical Impact.

To describe the prevalence, associated factors, and clinical impact of an initial negative herpes simplex virus (HSV) polymerase chain reaction (PCR) in critically ill patients with PCR-proven HSV encephalitis. Retrospective multicenter study from 2007 to 2017. Forty-seven French ICUs. Critically ill patients admitted to the ICU with possible/probable acute encephalitis and a positive cerebrospinal fluid (CSF) PCR for HSV. None. We included 273 patients with a median Glasgow Coma Scale score of 9 (6-12) at ICU admission. CSF HSV PCR was negative in 11 cases (4%), exclusively in lumbar punctures (LPs) performed less than 4 days after symptoms onset. Patients with an initial negative PCR presented with more frequent focal neurologic signs (4/11 [36.4%] vs 35/256 [13.7%]; p = 0.04) and lower CSF leukocytosis (4 cells/mm3 [3-25 cells/mm3] vs 52 cells/mm3 [12-160 cells/mm3]; p < 0.01). An initial negative PCR was associated with an increased delay between LP and acyclovir treatment (3 d [2-7 ] vs 0 d [0-0 d]; p < 0.01) and was independently associated with a poor neurologic outcome at hospital discharge (modified Rankin Scale score ≥ 4) (adjusted odds ratio, 9.89; 95% CI, 1.18-82.78). In severe herpes simplex encephalitis, initial negative CSF HSV PCR occurred in 4% of cases and was independently associated with worse neurologic outcome at hospital discharge. In these patients, a systematic multimodal diagnostic approach including early brain MRI and EEG will help clinicians avoid delayed acyclovir initiation or early inappropriate discontinuation.

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The authors have disclosed that they do not have any potential conflicts of interest.