Inflammatory reaction in progressive multifocal leukoencephalopathy: harmful or beneficial?

Progressive multifocal leukoencephalopathy (PML) occurs in patients with profound immunosuppression. Although lesions are usually devoid of lymphoplasmocytic infiltrates, inflammatory forms of PML have been described, in both human immunodeficiency virus (HIV)-seropositive (HIV+) and -seronegative (HIV-) patients. In addition, PML has been shown to develop in HIV+ patients shortly after introduction of highly active antiretroviral therapy (HAART), despite a recovery of the immune system. Therefore, one could postulate that PML might arise in the context of an immune reconstitution syndrome. To examine the clinical and neuroradiological characteristics of inflammatory forms of PML, the authors performed a retrospective analysis of the patients seen at their institution since 1996 as well as a review of the literature. Of 39 HIV+ and HIV- PML patients, 5 (13%) presented with an inflammatory form of this disease. Two HIV+ patients developed PML soon after the onset of HAART, concomitant to immune recovery, as demonstrated by a decrease of HIV viral load (VL) and an increase of CD4+ T-cell count. Three patients (2 HIV+ and 1 HIV-) had signs of inflammation in the central nervous system (CNS) characterized by contrast-enhancing lesions on neuroimaging studies, and/or inflammatory infiltrates on brain biopsy. The presence of JC virus-specific cytotoxic T lymphocytes was demonstrated in 4/4 patients tested and the outcome was favorable in 3 of them. In agreement with previously published case reports, the data indicate that inflammatory reactions in PML are not infrequent, and that they are generally associated with a favorable prognosis. Therefore clinicians should not disregard the diagnosis of PML in presence of contrast-enhancing brain lesions, and should use caution before treating these immunosuppressed individuals with steroids.