Long-Term Survival of Borna Disease Virus 1 (BoDV-1)-Encephalitis: An Exceptional Case with Valuable Insights for Pathophysiology and Disease Management.

INTRODUCTION: Borna disease virus 1 (BoDV-1) encephalitis has a (sub)acute and mostly fatal course. Initial flu-like symptoms are typically followed by rapid progressive panencephalitis and death within weeks. No curative therapy exists so far. We present a long-term survivor with distinctive clinical, imaging, and pathophysiological features. CASE PRESENTATION: A previously healthy male in his fifties was admitted in summer 2023 with (sub)acute encephalitis (cerebrospinal fluid, CSF: 132 cells/µl, no pathogen detection). Brain magnetic resonance imaging (MRI) demonstrated vasogenic edema affecting basal ganglia, temporal and limbic regions bilaterally. Despite high-dose steroids, the clinical condition of the patient slowly worsened. Three months later, BoDV-1 reactive antibodies were detected by elevated titers in CSF (1:320) and serum (1:5120). Treatment with favipiravir, corticosteroids, and mycophenolate mofetil (MMF) was initiated. After recovery for months, the patient developed progressive bilateral optic atrophy, cognitive decline, and a sleep disorder resembling Kleine-Levin syndrome. Translocator protein (TSPO)-PET revealed widespread microglial activation, confirmed by targeted cortical biopsy. Immunosuppressive therapy was escalated with anakinra, cyclophosphamide, and intrathecal dexamethasone, achieving temporary stabilization. In the summer of 2025, a severe brainstem syndrome emerged, accompanied by increased TSPO uptake in the brainstem and detection of BoDV-1 RNA in CSF for the first time. Despite another treatment with favipiravir and high-dose corticosteroids, the patient remained in a minimally conscious state. DISCUSSION: This exceptional case with long-term survival in BoDV-1 encephalitis gives important insights: BoDV1-associated neuroinflammation leading to a slowly progressive decline can be visualized by TSPO-PET. Late BoDV-1 RNA detection and subacute re-exacerbation after prolonged survival provides evidence that BoDV-1 persists in human brain tissue.