Afebrile HSV-2 Encephalitis with Radiographic Atypia and Minimal Systemic Inflammation: A Case Report

BACKGROUND Herpes simplex virus type 2 (HSV-2) is a rare cause of encephalitis, contributing to less than 2% of all HSV encephalitis cases. This report describes a case of HSV-2 encephalitis in an afebrile, immunocompetent woman who presented with atypical clinical and radiologic features, including multifocal cortical and subcortical T2 hyperintensities in the parietal, occipital, and frontal lobes, rather than the classic mesiotemporal involvement characteristic of HSV-1 encephalitis. CASE REPORT A 30-year-old woman with decompensated alcohol-related cirrhosis presented to the emergency department after an afebrile new-onset generalized tonic-clonic seizure lasting approximately 5 min. Magnetic resonance imaging of the brain demonstrated multifocal cortical and subcortical T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities, most prominent in the left parieto-occipital lobe, with trace restricted diffusion in this region and in the right parietal lobe. Additional hyperintense areas were observed in the left frontal, right occipital, and posterior left parietal lobes without corresponding diffusion restriction. Lumbar puncture was performed, and cerebrospinal fluid polymerase chain reaction testing showed HSV-2 positivity. The patient received intravenous acyclovir, resulting in clinical improvement, and was subsequently transferred to a skilled nursing facility to complete the treatment course. CONCLUSIONS This case illustrates that HSV-2 encephalitis can occur in immunocompetent, afebrile individuals and may manifest with non-classical imaging findings. Clinicians should include HSV-2 in the differential diagnosis of new-onset seizures, even in the absence of fever or typical limbic involvement. Early recognition and prompt initiation of antiviral therapy remain essential for favorable outcomes.