Fulminant Powassan Virus Encephalitis Presenting as Acute Ischemic Stroke: A Case Report.

Powassan virus (POWV) is a rare tick-borne flavivirus that can cause severe neuroinvasive disease with high morbidity and mortality. Early clinical and radiographic features are often nonspecific and may mimic acute ischemic stroke, leading to diagnostic delay. We report the case of a 77-year-old woman with recent tick exposure who presented with acute-onset focal neurologic deficits and fever. Initial neuroimaging demonstrated focal diffusion restriction, raising concern for acute ischemic stroke, and dual antiplatelet therapy was initiated. Over subsequent days, the patient developed progressive encephalopathy, persistent high-grade fevers, and worsening weakness. Repeat magnetic resonance imaging revealed rapidly evolving T2/FLAIR hyperintensities involving the basal ganglia, cortical gray matter, subcortical white matter, and cerebellum, consistent with viral encephalitis. Cerebrospinal fluid analysis demonstrated pleocytosis and elevated protein, and cerebrospinal fluid testing confirmed Powassan virus infection. Despite guideline-concordant empiric antimicrobial and antiviral therapy and aggressive supportive care, the patient experienced rapid neurologic decline requiring mechanical ventilation and ultimately progressed to quadriparesis and locked-in syndrome. Care was transitioned to comfort measures only, and the patient died shortly thereafter. This case highlights the aggressive clinical course of Powassan virus encephalitis and underscores its potential to mimic acute ischemic stroke in the early stages. In patients from endemic regions presenting with fever and rapidly progressive neurologic deficits, early consideration of Powassan virus and other arboviral encephalitides is essential to guide diagnostic evaluation and prognostication.