Central nervous system (CNS) infections can be caused by a variety of viruses, but in a significant number of patients no viral or other pathogen can be identified using routine diagnostic work-up. Interestingly, several case reports and series described Hepatitis E virus (HEV) as a potential pathogen. However, systematic studies have not been conducted so far.
We identified 243 patients from Southwestern Germany with acute CNS infections of unknown cause treated in our clinic between 2008 and 2018, of which serum and/or cerebrospinal fluid (CSF) samples were available. These patients were retrospectively tested for anti-HEV IgM and IgG antibodies. In addition, HEV PCR was performed in the majority of cases including IgM-negative patients with symptom onset <8 days. 263 healthy individuals served as controls.
Evidence of an acute HEV infection was found in four patients (1.7%). Three had recent HEV infection defined as positive anti-HEV IgM and IgG antibodies, one had current HEV infection defined as (additional) detection of HEV RNA in serum. However, anti-HEV IgM and IgG seroprevalence did not differ significantly from controls, though these had considerably lower IgM levels. Interestingly, anti-HEV IgG seroprevalence was unexpectedly high (30.7%) and revealed an age-dependent increase to more than 50% in patients older than 60 years.
This study supports previous findings that HEV could play a role in acute CNS infections. Therefore, we encourage testing for acute HEV infection if no other pathogen can be identified. However, further studies are necessary to prove a causal role.

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