BackgroundIsolated tumefactive demyelinating lesions (≥ 2 cm) may be difficult to distinguish from contrast enhancing brain tumors, central nervous system infections, and (rarely) tissue dysgenesis, which may all occur with increased signal on T2-weighted images. Establishing an accurate diagnosis is essential for management, and we delineate our single center experience. MethodsWe performed a retrospective review of medical records, imaging, and biopsy specimens for patients under 18 presenting with isolated tumefactive demyelination over a 10-year period. ResultsTen children (eight female) met inclusion criteria, with a median age of 14.1 years. Lesions were most likely to involve the thalamus (6/10), brainstem (5/10), basal ganglia (4/10) or corpus callosum (4/10). Eighty percent had perilesional edema at presentation and 60% had midline shift. Biopsies demonstrated demyelination with perivascular lymphocytic infiltration and axonal damage ranging from mild to severe. All patients were initially treated with high dose corticosteroids and 8/10 required additional medical therapies such as IVIG, plasmapheresis, cyclophosphamide, or rituximab. Increased intracranial pressure was managed aggressively with 2/10 patients requiring decompressive craniectomies. Clinical outcomes varied. ConclusionsSolitary tumefactive demyelinating lesions are rare and aggressive management of inflammation and increased intracranial pressure is essential. Biopsy is helpful to evaluate for other diagnoses on the differential and maximize therapies. Treatment beyond initial therapy with corticosteroids is often required. Isolated tumefactive demyelinating lesions are uncommon; multi-center natural history studies are needed to better delineate differential diagnoses and optimal therapies.