Brain MRI Features of Human Neuroinvasive Usutu Virus Infections

Background/Objectives: Neuroradiological features of neuroinvasive Usutu virus (USUV) infection are poorly understood, as current knowledge is largely limited to case reports. This study aimed to describe brain MRI patterns, and assess disease severity and vital and functional outcomes in patients with neuroinvasive USUV infection. Methods: This multicentric retrospective observational cohort study analyzed adult patients of both sexes, aged ≥18 years, in the continental region of Croatia who developed symptoms of neuroinvasive disease during the arbovirus transmission season between 2017 and 2025. Patients with serological and/or molecular confirmation of USUV infection were included in further analyses. Only patients who underwent a brain MRI during hospitalization were included in the study. Clinical data and blood/CSF laboratory parameters were also evaluated. The observed outcomes were the severity of clinical symptoms, vital status at hospital discharge, and functional status at hospital discharge. Results: Of 214 arbovirus-positive cases, 8 patients had confirmed neuroinvasive USUV infection, and 4 had a brain MRI. Three patients were male. One patient had a normal MRI, and three patients had abnormal MRIs. All patients with abnormal MRI demonstrated meningeal contrast enhancement (a finding not previously reported), uni- or bilateral hippocampal involvement suggestive of limbic encephalitis, and basal ganglia involvement. All patients required ICU admission, experienced prolonged hospitalization, and were discharged with moderate to severe disability. Conclusions: This study provides important insights into MRI patterns in patients with neuroinvasive USUV infection and addresses the current knowledge gap regarding the neuroimaging of this underdiagnosed disease.