Inflammatory progressive multifocal leukoencephalopathy in human immunodeficiency virus-negative patients

Objective Inflammatory progressive multifocal leukoencephalopathy (iPML) with enhancing magnetic resonance imaging (MRI) lesions and leukocyte infiltration occurs in human immunodeficiency virus (HIV)–infected individuals after highly active antiretroviral therapy (HAART) treatment. MRI diagnostic criteria for PML suggest that iPML does not occur in HIV‐negative individuals. Methods We studied pathologically proved PML (12 by biopsy, 9 with MRI, 32 at autopsy). Results HIV‐negative (2/5) and ‐positive (2/4) PML patients had enhancing MRI lesions, correlated with CD3+ lymphocyte infiltration. Inflammatory infiltrates occurred in the majority of HIV‐negative (7/8) and HIV‐positive/HAART (17/20) cases (p > 0.2), but in only 2 of 16 HIV‐positive/non‐HAART cases (p < 0.001). Interpretation iPML showed radiographic and pathological similarity in HIV‐positive/HAART and HIV‐negative patients. HIV‐negative iPML necessitates further consideration of MRI criteria for PML. Ann Neurol 2007