• Etienne de Montmollin, Claire Dupuis, Pierre Jaquet, Benjamine Sarton, Charline Sazio, Vincent Susset, Marie Conrad, Laurent Argaud, Sophie Demeret, Jean Marc Tadié, François Barbier, Michel Wolff, Jean-François Timsit, Benoit Visseaux, Romain Sonneville, and ENCEPHALITICA Study Group.
• INSERM UMR 1137, Université de Paris, Sorbonne Paris Cité, Paris, France.
• Crit. Care Med. 2022 Jul 1; 50 (7): e643e648e643-e648.

ObjectivesTo 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.DesignRetrospective multicenter study from 2007 to 2017.SettingForty-seven French ICUs.PatientsCritically ill patients admitted to the ICU with possible/probable acute encephalitis and a positive cerebrospinal fluid (CSF) PCR for HSV.InterventionsNone.Measurements And Main ResultsWe 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).ConclusionsIn 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.Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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