The differential diagnosis in this patient includes primary angiitis of the central nervous system, vasculitis, giant cell arteritis, and infection by a broad range of viruses, fungi, Mycobacterium tuberculosis, and other protozoa. On admission, lumbar puncture showed an elevated opening pressure (44 cm H2O), protein level of 131 mg/dL, glucose level of 57 mg/dL, and 39 nucleated cells (69% lymphocytes, 12% neutrophils, 15% monocytes, and 4% plasma cells). Results of Gram staining, acid-fast staining, and oncotic cytologic analysis were negative. The VDRL test results were nonreactive. Cultures for fungi and M tuberculosis were negative. After lumbar puncture, this patient was treated for presumed herpes encephalitis with intravenous acyclovir without resolution. The patient died 15 days after hospital admission. Histopathologic analysis revealed extensive areas of necrosis and hemorrhage in the cerebellum, fibrinoid necrotizing panarteritis, some thrombosis, granulomatous lymphoplasmacytic inflammatory infiltrate, foamy macrophages, isolated multinucleated giant cells, and incipient formation of perivascular granulomas. Different structures (isolated or forming small clusters) with the morphological characteristics of amoeba trophozoites were identified in the vascular wall and in areas with and without an inflammatory reaction (Figure 2). The patient had no skin lesions; the probable route of invasion of the pathogen might have been the respiratory tract, followed by hematogenic dissemination to the central nervous system.