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Chronic necrotizing granulomatous meningoencephalitis is an idiopathic inflammatory disease with possible autoimmune mediated delayed type hypersensitivity response. It commonly affects the central nervous system of dogs, and on rare occasions cats. However, this inflammatory disease has rarely been reported in humans. A 69-year-old woman presented with subacute intermittent sharp headaches. Brain MRI revealed multifocal enhancing lesions and edema as well as multifocal signal abnormality throughout the supratentorial and infratentorial parenchyma. Cerebrospinal fluid showed elevated opening pressure, pleocytosis, and elevated protein. MRA head, MRV head, cerebral angiogram, extensive serum and CSF work up for infectious and autoimmune etiologies were also unremarkable. Brain biopsy revealed necrotizing granulomatous inflammation with dystrophic calcification. High dose of methylprednisolone followed by a 6-week prednisone taper resolved her headache and the brain MRI abnormalities. This case demonstrates the response of necrotizing granulomatous meningoencephalitis in humans to steroids.