Inflammatory Cortical Demyelination in Early Multiple Sclerosis
By C. Lucchinetti, Bogdan F Popescu, R. Bunyan, N. Moll, S. Roemer, Hans Lassmann, Wolfgang Brück, Joseph E. Parisi, B. Scheithauer, C. Giannini and 3 more. New England Journal of Medicine, 2011
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BACKGROUND Cortical disease has emerged as a critical aspect of the pathogenesis of multiple sclerosis, being associated with disease progression and cognitive impairment. Most studies of cortical lesions have focused on autopsy findings in patients with long-standing, chronic, progressive multiple sclerosis, and the noninflammatory nature of these lesions has been emphasized. Magnetic resonance imaging studies indicate that cortical damage occurs early in the disease. METHODS We evaluated the prevalence and character of demyelinating cortical lesions in patients with multiple sclerosis. Cortical tissues were obtained in passing during biopsy sampling of white-matter lesions. In most cases, biopsy was done with the use of stereotactic procedures to diagnose suspected tumors. Patients with sufficient cortex (138 of 563 patients screened) were evaluated for cortical demyelination. Using immunohistochemistry, we characterized cortical lesions with respect to demyelinating activity, inflammatory infiltrates, the presence of meningeal inflammation, and a topographic association between cortical demyelination and meningeal inflammation. Diagnoses were ascertained in a subgroup of 77 patients (56%) at the last follow-up visit (at a median of 3.5 years). RESULTS Cortical demyelination was present in 53 patients (38%) (104 lesions and 222 tissue blocks) and was absent in 85 patients (121 tissue blocks). Twenty-five patients with cortical demyelination had definite multiple sclerosis (81% of 31 patients who underwent long-term follow-up), as did 33 patients without cortical demyelination (72% of 46 patients who underwent long-term follow-up). In representative tissues, 58 of 71 lesions (82%) showed CD3+ T-cell infiltrates, and 32 of 78 lesions (41%) showed macrophage-associated demyelination. Meningeal inflammation was topographically associated with cortical demyelination in patients who had sufficient meningeal tissue for study. CONCLUSIONS In this cohort of patients with early-stage multiple sclerosis, cortical demyelinating lesions were frequent, inflammatory, and strongly associated with meningeal inflammation. (Funded by the National Multiple Sclerosis Society and the National Institutes of Health.)
Subfields: Developmental Neuroscience, Neurology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/b2ea12f2509ec317385ac41e76728b35ae2e6ddf
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Citations in the corpus
- Multiple Sclerosis Pathology. (2018, background): “Cortical demyelination is already present in the earliest stages of MS (Lucchinetti et al. 2011), but its extent massively increases when patients reach the progressive stage (Kutzelnigg et al.”
- Pathogenic Mechanisms Associated With Different Clinical Courses of Multiple Sclerosis (2019, background): “Cortical lesions, including the subpial lesions, may already arise in the early stages of MS, being present in brain biopsies or autopsies of patients with a disease duration of weeks to months (82), but the number and size increases with disease duration, thus being most extensive in patients with ”