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Hepatitis E virus (HEV) is a common zoonotic infection associated with pigs which is endemic in many developed countries. Most infections are asymptomatic, with only a minority causing clinically evident hepatitis. Numerous extra-hepatic manifestations are associated with HEV, most commonly neurological injury. The aim of the study was to explore the relationship between HEV and acute neurological illness.464 consecutive patients presenting to 4 centres in the UK, France and the Netherlands with acute non-traumatic neurological illnesses were prospectively tested for HEV by serology and PCR.11/464 patients (2.4%) had evidence of current/recent HEV infection. Neurological cases in which HEV infection was found included neuralgic amyotrophy (n=3, all PCR positive); cerebrovascular event (n=4); seizure (n=2); encephalitis (n=1); and an acute combined facial and vestibular neuropathy (n=1). Symptoms of hepatitis were mild and no patients were clinically jaundiced.The 3 cases of HEV associated neuralgic amyotrophy had similarities with other previously described HEV-associated cases; all were middle-aged males with bilateral involvement of the brachial plexus. This observation supports a causal relationship between HEV and neuralgic amyotrophy. To further understand the relevance of HEV infection in patients with acute neurological illnesses, case control studies are warranted.