Multifocal necrotizing leukoencephalopathy with pontine predilection in immunosuppressed patients: a clinicopathologic review of 16 cases.

ABSTRACT

Multifocal necrotizing leukoencephalopathy (MNL) is characterized by multiple, usually microscopic, foci of necrosis confined primarily to the white matter of the basis pontis, but sometimes found elsewhere in the central nervous system. All 16 patients in whom we identified MNL had underlying immunosuppression, either naturally occurring or iatrogenic, including the acquired immunodeficiency syndrome (seven patients), acute leukemias (four patients), and lymphoma (one patient). One patient each had severe combined immunodeficiency, orthotopic liver transplantation, Shwachman-Diamond syndrome, and idiopathic thrombocytopenic purpura treated with high-dose steroids. Histologically, lesions of MNL show demyelination, spongiosis, axonal swelling, minimal histiocytic infiltrates, and frequent axonal calcification. Multifocal necrotizing leukoencephalopathy lesions were found in the pons of all patients, most commonly in the crossing pontocerebellar fibers, but often in the descending white matter tracts and rarely in the tegmentum. Three cases also showed nonpontine foci of MNL involving the white matter of the medulla, cerebellum, and cerebral hemispheres. Multifocal necrotizing leukoencephalopathy is a distinct entity usually localized to the basis pontis and is most consistently associated with immunosuppression, but as yet lacks other clearly defined clinical correlates.