Neurological manifestation of HEV infection: still a rare disease entity?

Hepatitis E virus (HEV) infection is the most common form of viral hepatitis and is reported to cause neurological manifestation in up to 30% of diagnosed infections. We evaluated the medical reports of all patients (n = 29,994) who were discharged from the Department of Neurology of Ulm University between 01.01.2015 and 30.09.2022 to detect neurological manifestations of HEV. In addition, we retrospectively analyzed the serum samples of n = 99 patients representing different neurological diseases possibly related to HEV for anti-HEV-IgM and anti-HEV-IgG. At the time of discharge from hospital, the etiology of neurological symptoms in these patients was unclear. Overall, five cases of extrahepatic neurological manifestation of HEV (defined as anti-HEV-IgM and HEV-IgG positive) could be detected. An increase of both, anti-IgM- and anti-IgG-serum levels was significantly more common in neuralgic amyotrophy/plexus neuritis/radiculitis than in AIDP/CIDP (P = 0.01), meningitis/encephalitis (P = 0.02), idiopathic peripheral facial paralysis (P = 0.02) and tension headache (P = 0.02). In 15% (n = 15 out of 99) of retrospectively analyzed serum samples, conspicuous positive anti-HEV-IgG levels were detected. This finding was most common in AIDP/CIDP. In conclusion, results of this study indicate neurological manifestation of HEV to be a rare but still underestimated course of disease, occurring at any age and gender. Therefore, testing for HEV should be considered in patients with neurological symptoms of unknown origin, especially in those with neuralgic amyotrophy/plexus neuritis.