Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions

Abstract

Abstract Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that causes motor, sensory, and cognitive deficits. The present study characterized demyelinated lesions in the cerebral cortex of MS patients. One hundred twelve cortical lesions were identified in 110 tissue blocks from 50 MS patients. Three patterns of cortical demyelination were identified: type I lesions were contiguous with subcortical white matter lesions; type II lesions were small, confined to the cortex, and often perivascular; type III lesions extended from the pial surface to cortical layer 3 or 4. Inflammation and neuronal pathology were studied in tissue from eight and seven patients, respectively. Compared to white matter lesions, cortical lesions contained 13 times fewer CD3‐positive lymphocytes (195 vs 2,596/mm 3 of tissue) and six times fewer CD68‐positive microglia/macrophages (11,948 vs 67,956/mm 3 of tissue). Transected neurites (both axons and dendrites) occurred at a density of 4,119/mm 3 in active cortical lesions, 1,107/mm 3 in chronic active cortical lesions, 25/mm 3 in chronic inactive cortical lesions, 8/mm 3 in myelinated MS cortex, and 1/mm 3 in control cortex. In active and chronic active cortical lesions, activated microglia closely apposed and ensheathed apical dendrites, neurites, and neuronal perikarya. In addition, apoptotic neurons were increased significantly in demyelinated cortex compared to myelinated cortex. These data support the hypothesis that demyelination, axonal transection, dendritic transection, and apoptotic loss of neurons in the cerebral cortex contribute to neurological dysfunction in MS patients.