Recurrent Ischemic Strokes Caused by HSV-2-Associated Cerebral Vasculitis in Antisynthetase Syndrome

BACKGROUND Antisynthetase syndrome is a rare autoimmune disease characterized by anti-aminoacyl-tRNA synthetase autoantibodies and clinical features including interstitial lung disease, myositis, and arthritis, requiring immunosuppressive treatment. We report a case of a patient with antisynthetase syndrome who developed a severe herpes simplex virus 2 (HSV-2) encephalitis with vasculitis and recurrent strokes. CASE REPORT A 76-year-old woman with antisynthetase syndrome on rituximab, mycophenolate mofetil, and prednisone presented with progressive headache, confusion, and gait disturbance. MRI demonstrated bilateral temporal cortical hyperintensities consistent with encephalitis, as well as acute ischemic lesions in the left middle cerebral artery territory. Cerebrospinal fluid analysis showed HSV-2 DNA. Despite intravenous acyclovir, the patient developed aphasia and left-sided neglect. Repeated MRI revealed middle cerebral artery branch occlusion and concentric vessel wall enhancement, consistent with central nervous system vasculitis and multiple acute infarcts. On further follow-up, serial cerebrospinal fluid testing showed delayed viral clearance over 7 weeks. Management included acyclovir and discontinuation of rituximab to allow immune system recovery. Empiric antiplatelet therapy and antiepileptic therapy were added because of suspected intermittent epileptic seizures, with epileptogenic potentials identified on electroencephalogram. After 9 weeks of treatment and rehabilitation, the patient reached partial neurological recovery. Despite residual mild left gaze palsy and fatigue, she regained full functional independence in all activities of daily living. CONCLUSIONS To the best of our knowledge, this is the first reported case of a patient with antisynthetase syndrome who developed HSV-2 encephalitis complicated by vasculitis and recurrent ischemic strokes. Immunosuppressive treatment may have contributed to delayed HSV-2 clearance, necessitating prolonged acyclovir therapy.