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Vigabatrin (VG, adrenocorticotropic hormone (ACTH), and prednisone are first-line treatments for infantile spasms (IS). A recent study reported benefits from the use of combination VGB and hormonal therapy over hormonal treatment alone in IS. We describe three patients with IS who developed acute encephalopathy with extrapyramidal symptoms, vigabatrin-associated brain abnormalities on magnetic resonance imaging (VABAM), and death in one patient shortly after initiation of therapy with VGB and ACTH. A literature review supports increased