Inflammatory cortical demyelination in early multiple sclerosis.
Open accessAbstract
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.).
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Early lesions have been associated with prominent microglial activation.
“This may well reflect the greater microglia and astrocyte activity in the white matter; pure cortical lesions in post-mortem tissues show little or no inflammation (Bo et al., 2004; Brink et al., 2005; van Horssen et al., 2007), although early lesions have been associated with prominent microglial activation (Lucchinetti et al., 2011).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Lucchinetti et al., 2011
Biopsies taken from early MS patients with cortical demyelination were more likely to have leptomeningeal inflammation, consisting of effector T cells and IgA B cells infiltrates, than those without cortical demyelination, and the severity of cortical lesions is correlated to the extent of meningeal inflammation.
“Biopsies taken from early MS patients with cortical demyelination were more likely to have leptomeningeal inflammation, consisting of effector T cells and IgA B cells infiltrates, than those without cortical demyelination.”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Lucchinetti et al., 2011
The leptomeninges are a key player in multiple sclerosis (MS), and in both MS patients and MS mouse models, immune cells infiltrate the leptomeninges and pathology is commonly seen in cortical areas adjacent to the meninges.
“The leptomeninges are now recognized as a key player in multiple sclerosis (MS), an inflammatory CNS autoimmune disorder characterized by axon demyelination”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Lucchinetti et al., 2011
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- Authors
- Lucchinetti, C. F., Popescu, B. F. G., Bunyan, R. F., Moll, N. M., Roemer, S. F., Lassmann, H., Brück, W., Parisi, J. E., Scheithauer, B. W., Giannini, C., Weigand, S. D., Mandrekar, J., & Ransohoff, R. M.
- Affiliations
- Mayo Clinic (US)
- Cleveland Clinic Research (US)
- Medical University of Vienna (AT)
- Universitätsmedizin Göttingen (DE)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2011-12-08
- Volume
- 365
- Issue
- 23
- Pages
- 2188-2197
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC3282172
- OpenAlex
- W2113948549
- Cited by
- 1,103
- References
- 50
- Citations by year
- 2026: 37 · 2025: 44 · 2024: 69 · 2023: 70 · 2022: 68 · 2021: 104 · 2020: 75 · 2019: 83 · 2018: 64 · 2017: 72 · 2016: 75 · 2015: 84 · 2014: 89 · 2013: 100 · 2012: 67
- FWCI
- 58.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Funders
- National Multiple Sclerosis Society (RG3185-B-3)
- Multiple Sclerosis Society
- National Institutes of Health (P50NS38667)
- National Institute of Neurological Disorders and Stroke (P50NS38667, P50NS038667, R01NS049577)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Oncology › Polyomavirus and related diseases
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- multiple sclerosis, cortical demyelination, inflammatory demyelination, meningeal inflammation, cortical lesions, early multiple sclerosis, white matter lesions, stereotactic biopsy, disease progression
- MeSH terms
- Biopsy, Cerebral Cortex, Humans, Inflammation, Multiple Sclerosis, Prevalence, Logistic Models, Neurodegenerative Diseases
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