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Abstract
Objective: To characterize pathologic changes in the cerebral cortex of patients with multiple sclerosis (MS) and progressive multifocal leukoencephalopathy (PML).
Methods: Autopsy brain tissue was obtained from 13 patients with PML, 4 patients with MS, 2 patients with HIV encephalopathy, and 1 subject without neurologic pathology. Immunohistochemistry for myelin proteins, inflammatory cells, and neurofilaments was performed to evaluate the distribution of cortical lesions, their inflammatory activity, and neuritic pathology. Confocal microscopy was applied to examine pathologic changes in neurites in PML cortex.
Results: Leukocortical, intracortical, and subpial patterns of cortical demyelination were represented in MS brain tissue. In PML brain tissue intracortical and leukocortical but not subpial lesions were observed. Cortical lesions in PML and MS contained fewer inflammatory cells than demyelinated areas in the white matter. Neuritic pathology in cortical PML lesions was represented by dystrophic and transected neurites. Pathologic modifications in neuritic processes in PML were more evident in highly inflamed white matter than in gray matter areas of demyelination, reminiscent of previous reports of neuritic pathology in MS. JC virus-infected cells were associated with PML white matter, leukocortical and intracortical lesions.
Conclusions: Cortical pathology represents a distinct feature of progressive multifocal leukoencephalopathy. Similarities and differences with regard to multiple sclerosis cortical pathology were noted and may be informative regarding the pathogenesis of both disorders.
GLOSSARY: AP = alkaline phosphatase; DAB = diaminobenzidine; HAART = highly active antiretroviral therapy; HIVE = HIV encephalopathy; MBP = myelin basic protein; MS = multiple sclerosis; NNTC = NeuroAIDS Tissue Consortium; PLP = proteolipid protein; PML = progressive multifocal leukoencephalopathy; SPMS = secondary progressive multiple sclerosis; X-ALD = X-linked adrenoleukodystrophy.
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- Cortical demyelination in PML and MS: Similarities and differences
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