Document Detail


Inflammatory cortical demyelination in early multiple sclerosis.
MedLine Citation:
PMID:  22150037     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.).
Authors:
Claudia F Lucchinetti; Bogdan F G Popescu; Reem F Bunyan; Natalia M Moll; Shanu F Roemer; Hans Lassmann; Wolfgang Brück; Joseph E Parisi; Bernd W Scheithauer; Caterina Giannini; Stephen D Weigand; Jay Mandrekar; Richard M Ransohoff
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The New England journal of medicine     Volume:  365     ISSN:  1533-4406     ISO Abbreviation:  N. Engl. J. Med.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-14     Completed Date:  2011-12-20     Revised Date:  2012-03-15    
Medline Journal Info:
Nlm Unique ID:  0255562     Medline TA:  N Engl J Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2188-97     Citation Subset:  AIM; IM    
Affiliation:
Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. lucchinetti.claudia@mayo.edu
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MeSH Terms
Descriptor/Qualifier:
Biopsy
Cerebral Cortex / immunology,  pathology*
Humans
Inflammation / pathology*
Logistic Models
Multiple Sclerosis / immunology,  pathology*
Neurodegenerative Diseases / pathology
Prevalence
Grant Support
ID/Acronym/Agency:
1R01NS049577/NS/NINDS NIH HHS; P50 NS038667-13/NS/NINDS NIH HHS; P50NS38667/NS/NINDS NIH HHS; R01 NS049577-07/NS/NINDS NIH HHS
Comments/Corrections
Comment In:
N Engl J Med. 2011 Dec 8;365(23):2231-3   [PMID:  22150043 ]
Nat Rev Neurol. 2012 Feb;8(2):61   [PMID:  22249838 ]

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