Cited by 1,103Multiple Sclerosis Research StudiesPolyomavirus and related diseasesNeuroinflammation and Neurodegeneration Mechanisms

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Inflammatory cortical demyelination in early multiple sclerosis.

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Lucchinetti, Claudia F., Popescu, Bogdan F.G., Bunyan, Reem F., Moll, Natalia M., Roemer, Shanu F., Lassmann, Hans, Brück, Wolfgang, Parisi, Joseph E., Scheithauer, Bernd W., Giannini, Caterina, Weigand, Stephen D., Mandrekar, Jay, Ransohoff, Richard M.·2011·New England Journal of Medicine

DOI 10.1056/nejmoa1100648PMC PMC3282172

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Abstract

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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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: Lucchinetti, Claudia F.
Popescu, Bogdan F.G.
Roemer, Shanu F.
Lassmann, Hans
Brück, Wolfgang
Parisi, Joseph E.
Giannini, Caterina
Weigand, Stephen D.
Mandrekar, Jay
Ransohoff, Richard M.
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
DOI: 10.1056/nejmoa1100648
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 › Clinical Neurology › 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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Inflammatory cortical demyelination in early multiple sclerosis.

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