Clinical question: Does delay in diagnosis of herpes simplex virus (HSV) encephalitis due to negative initial cerebrospinal fluid (CSF) studies affect neurologic outcomes?
Background: Case reports and series have demonstrated poor outcomes for patients in whom diagnosis and treatment of HSV encephalitis have been delayed, though frequency and severity have not been reported.
Study design: Retrospective study
Setting: French intensive care units (ICUs)
Synopsis: This study was a secondary analysis of a retrospective database of 273 patients with confirmed HSV encephalitis admitted to 47 ICUs. On initial lumbar puncture, 11 cases (4%) had negative HSV polymerase chain reaction (PCR) tests and 43 cases (16.5%) had normal CSF leukocyte count. All the false-negative PCR tests occurred when the lumbar puncture had been performed within four days of symptom onset. Patients with negative PCRs were more likely to have atypical presentations with focal neurologic deficits (4/11 [36.4%] versus 35/256 [13.7%]; P=0.04), as well as to have lower CSF leukocyte counts. This corresponded with delayed time to treatment with acyclovir (3 d [2–7 d] versus 0 d [0–0 d]; P<0.01) and higher rates of modified Rankin Score ≥4 at hospital discharge (10/11 [90.9%] versus 91/262 [34.7%]; P<0.01). This study is limited by both its retrospective nature and its small sample size.
Bottom line: When an alternative diagnosis is not evident in patients with a highly suspicious presentation for HSV and early negative CSF studies, clinicians should pursue a multimodal approach to diagnosis (e.g., MRI, EEG) and discontinue empiric treatment with caution, given the risks of worsened neurologic outcomes.
Citation: de Montmollin E, et al. herpes simplex virus encephalitis with initial negative polymerase chain reaction in the cerebrospinal fluid: prevalence, associated factors, and clinical impact [published online ahead of print, 2022 Feb 2]. Crit Care Med. 2022 Feb 2. doi:10.1097/CCM.0000000000005485.
Dr. Bartlett is a third-year internal medicine resident at Maine Medical Center, Portland, Maine, who’s pursuing a career in hospital medicine.