To present two fulminant cases of suspected Susac syndrome refractory to immunomodulatory therapy.

Susac syndrome (SS) is a presumed immune-mediated endotheliopathy characterized by a triad of encephalopathy, hearing loss, and branch retinal artery occlusions (BRAO). SS may vary in clinical presentation and course and yet typically responds to immunosuppressive therapy. Fatal cases of SS have been rarely reported.

We describe two cases, 15 years apart, of suspected malignant SS.

Our patients, a 36-year-old man and a 35-year-old woman presented with several symptoms including encephalopathy, hearing loss, and, in one case, blurred vision. Neither demonstrated BRAO. The first patient had a positive toxicology screen for methamphetamines. The second patient had a history of hypertension and morbid obesity. Serial MRIs demonstrated progressive scattered punctate foci of restricted diffusion throughout the brain, including the cerebrum, corpus callosum, brainstem, and cerebellum. An area of leptomeningeal enhancement was appreciated in our second patient. Extensive workup in both cases failed to yield an alternative diagnosis.

Our patients were treated with high-dose intravenous methylprednisolone and intravenous immunoglobulin without improvement. The second patient also received intravenous cyclophosphamide, aspirin, clopidogrel, therapeutic heparin, and rituximab. Both declined in the hospital despite treatment and died shortly following withdrawal of life-sustaining treatments: the man on hospital day 25 and woman on hospital day 42.

Autopsy in both cases demonstrated innumerable microscopic and lacunar infarcts of varying ages throughout the brain, interpreted as most consistent with SS. 

These cases highlight an uncommon aggressive variant of suspected SS leading to death within weeks of symptom onset despite intensive therapies. SS poses a diagnostic and treatment dilemma particularly in patients with a fulminant course.