Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions
Article first published online: 15 JUL 2001
Copyright © 2001 Wiley-Liss, Inc.
Annals of Neurology
Volume 50, Issue 3, pages 389–400, September 2001
How to Cite
Peterson, J. W., Bö, L., Mörk, S., Chang, A. and Trapp, B. D. (2001), Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol., 50: 389–400. doi: 10.1002/ana.1123
- Issue published online: 31 AUG 2001
- Article first published online: 15 JUL 2001
- Manuscript Accepted: 9 MAY 2001
- Manuscript Revised: 2 APR 2001
- Manuscript Received: 5 FEB 2001
- National Institutes of Health. Grant Number: RO1 NS35058
- NINDS. Grant Number: NS07291
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/mm3 of tissue) and six times fewer CD68-positive microglia/macrophages (11,948 vs 67,956/mm3 of tissue). Transected neurites (both axons and dendrites) occurred at a density of 4,119/mm3 in active cortical lesions, 1,107/mm3 in chronic active cortical lesions, 25/mm3 in chronic inactive cortical lesions, 8/mm3 in myelinated MS cortex, and 1/mm3 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.