Initial Presentation Not Associated With Pathogen in Infectious Encephalitis

Despite the availability of new tools for diagnosing infectious encephalitis, no initial clinical, biological, or imaging pattern was identifiable at admission among patients hospitalized with encephalitis of unknown cause, according to the results of a study published in Clinical Infectious Disease.

A team of French investigators attempted to find similar patterns among clusters of patients with encephalitis of unknown cause with a goal of determining if initial presentation may be predictive of encephalitis etiology. The researchers studied data from patients with documented or suspected acute infectious encephalitis from the national cohort of infectious encephalitis in France, an ongoing prospective cohort study started in 2016.

Data from 349 patients were analyzed as of August 1, 2018. The investigators identified herpes simplex virus (25%), varicella zoster virus (11%), tick-borne encephalitis virus (6%), listeria (5%), and influenza virus (3%) as the most common pathogens; however,  encephalitis of unknown cause was reported for 34% of cases. Factor analysis of mixed data looking for a pattern of association between the initial presentation of the patient and the etiologic pathogen was performed; no specific pattern related to the group of patients with encephalitis of unknown cause was identified. Several factors including age, temporal or hemorrhagic lesions, and cerebral spinal fluid lymphocytosis were significantly associated with herpes simplex virus and varicella zoster virus encephalitis.

The investigators note several study limitations, including a lack of standardization of assessments in this observational study. As a result of this limitation, they were unable to ensure that all unknown etiologies were fully investigated according to current recommendations. Also, selection bias cannot be excluded as some institutions included more cases than others.

The investigators conclude that despite improvements in noninvasive diagnostic procedures and technical progress that allows for better identification of the pathogen contributing to documented or suspected infectious acute encephalitis, initial presentation was not associated with any etiologic pathogen. “This study confirms that the initial clinical and paraclinical approach is not valuable enough to reconsider the worldwide recommendations for an early empirical treatment (acyclovir and amoxicillin) of encephalitis and maintain it until reception of microbiological diagnosis.”


Le Maréchal M, Mailles A, Seigneurin A, Tattevin P, Stahl JP, Épaulard O; on behalf of the ESCMID Study Group on Infections of the Brain. A prospective cohort study to identify clinical, biological and imaging features that predict etiology of acute encephalitis [published online May 20, 2020]. Clin Infect Dis. doi: 10.1093/cid/ciaa598