To highlight the appearance of fungal-related stroke on MRI and to increase awareness of opportunistic CNS infection as an etiology of cryptogenic stroke in patients receiving immunomodulatory therapies

Over a third of strokes are cryptogenic. Identifying the etiology of stroke is a crucial step in reducing the incidence and associated morbidity and mortality of recurrent stroke. Opportunistic CNS infection is a well-documented cause of stroke. The development and increasingly widespread use of high-efficacy immunomodulatory drugs requires vigilance for opportunistic infection and associated complications in patients receiving these drugs.

A case report

A 65-year-old gentleman with Waldenstrom's macroglobulinemia on zanubrutinib complicated by biopsy-confirmed AHL amyloidosis, which was further complicated by cardiomyopathy, nephropathy, and recurrent pleural effusions presented with encephalopathy and was found to have multifocal acute, symmetric, subcortical strokes. There was no evidence of prior strokes or chronic small vessel disease on MRI. A comprehensive stroke work-up was unremarkable, including typical vascular risk factors within goal, negative blood cultures, normal d-dimer, normal serum viscosity, no radiographic evidence of large vessel disease, and no arrhythmia on telemetry. Echocardiogram showed bi-atrial enlargement related to cardiac amyloid, but no evidence of atrial, ventricular, or perivalvular thrombus. Lumbar puncture was performed and revealed WBC 10, RBC 9, glucose 16, and protein 154. Cryptococcal antigen was positive at a titer of 1:64. Amphotericin B and flucytosine were initiated with clinical improvement over two weeks and he was transitioned to fluconazole for maintenance therapy and prophylaxis.

This case describes a patient treated with zanubrutinib who developed cryptococcal meningitis causing multifocal acute, symmetric, subcortical strokes. Small molecule tyrosine kinase inhibitors are associated with increased relative risk of opportunistic infection, including CNS fungal infections. Opportunistic CNS infection should be considered as a potential cause of cryptogenic stroke in patient’s receiving these drugs.