West Nile virus neuroinvasive disease: Clinical characteristics and prognostic factors

Background: In 2024, Israel experienced its largest West Nile Virus (WNV) outbreak, with 922 confirmed cases. WNV is a leading global cause of viral encephalitis. This study aimed to identify clinical features and prognostic factors associated with neuroinvasive WNV in hospitalized patients. Methods: We retrospectively reviewed hospitalized patients with confirmed WNV at a tertiary center in Israel (January–September 2024). Patients were categorized as neuroinvasive or non-neuroinvasive. Demographic, clinical, and outcome data were analyzed. Primary outcome was 16-week mortality; secondary was functional decline (modified Rankin Scale, mRS). Results: Of 166 hospitalized patients, 93 (56 %) had neuroinvasive WNV, primarily encephalitis (90 %). Neuroinvasive disease was linked to higher mortality (36 % vs. 13 %, p < 0.01) and worse functional outcomes (median mRS 4 ± 2 vs. 2 ± 2, p = 0.02). No significant differences in age, sex, comorbidities, or immunosuppression were found between groups. Among neuroinvasive cases, encephalitis, seizures, and autonomic dysfunction were associated with poorer outcomes. Lower pre-morbid function did not predicted greater decline. EEG in 28 encephalitis patients showed abnormalities in 71 %, mainly diffuse slowing; epileptiform activity was rare. Quantitative EEG revealed increased delta power and more frequent paroxysmal slow wave events(PSWE), which correlated with worse functional status. Conclusions: Neuroinvasive WNV is associated with substantial morbidity and mortality. Traditional risk factors like age were not predictive of poor outcomes. Instead, clinical features such as autonomic dysfunction and novel markers like quantitative EEG abnormalities may serve as valuable prognostic tools. These findings underscore the need for improved risk stratification strategies in WNV neuroinvasive disease.