Toscana virus associated with Guillain-Barré syndrome: a case-control study

Guillain-Barré syndrome (GBS) is an acute-onset, immune-mediated polyradiculoneuropathy, often precipitated by an antecedent infection. An association of GBS with vector-borne viral infections has been suggested, with evidence for the involvement of Zika, Dengue, Chikungunya and West Nile virus (WNV). This prospective case-control study was conducted to identify vector-borne viral infections in GBS. Thirteen individuals newly diagnosed as GBS were enrolled. Disease severity, prognostic factors and nerve conduction patterns were assessed. Eleven individuals with non-infectious conditions requiring cerebrospinal fluid (CSF) analysis were included as controls. Plasma, CSF and urine specimens were evaluated via nucleic acid amplification assays aimed to detect a broad spectrum of viruses. WNV and Toscana virus (TOSV) IgM/IgG antibodies were screened using commercial immunofluorescence assays and confirmed via virus neutralization tests (VNT). Partial TOSV nucleocapsid and genotype 1 polymerase sequences were detected in CSF of a patient with normal pressure hydrocephalus. Two control subjects had VNT-confirmed TOSV IgM in plasma. VNT-confirmed WNV and TOSV IgG were detected in 15.4% and 61.5% of GBS patients, respectively. Variations in WNV IgG and TOSV IgM detection rates were not statistically significant among study cohorts. However, TOSV IgG was significantly more frequent in GBS patients. No difference was observed for disease form or prognostic scores for virus markers. Follow-up serological profiles were identical to the initial findings. We have identified TOSV as a potential precipitating agent in GBS, with some rare clinical presentations of symptomatic TOSV infections.