It has been shown that hepatitis E virus (HEV) may be responsible for chronic hepatitis in solid-organ transplant patients. It has also been suggested that HEV may be responsible for atypical neurological symptoms during the acute phase. However, the relationship between the neurological symptoms and HEV infection was based on the detection of anti-HEV IgM in the sera. Herein, we report a case where neurological symptoms, that is peripheral nerve involvement with proximal muscular weakness that affected the four limbs joints with central nervous-system involvement and bilateral pyramidal syndrome, occurred in a kidney-transplant patient who was chronically infected by HEV. For the first time, HEV RNA was detected in the serum and cerebrospinal fluid. In addition, clonal HEV sequences were analyzed in both compartments, that is serum and cerebrospinal fluid. The discovery of quasispecies compartmentalization and its temporal association suggests that neurological symptoms could be linked to the emergence of neurotropic variants.