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Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination

Lucchinetti, Claudia, Br�ck, Wolfgang, Parisi, Joseph, Scheithauer, Bernd, Rodriguez, Moses, Lassmann, Hans·2000·Annals of Neurology
DOI 10.1002/1531-8249(200006)47:6%3c707::aid-ana3%3e3.0.co;2-q
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Abstract

Multiple sclerosis (MS) is a disease with profound heterogeneity in clinical course, neuroradiological appearance of the lesions, involvement of susceptibility gene loci, and response to therapy. These features are supported by experimental evidence, which demonstrates that fundamentally different processes, such as autoimmunity or virus infection, may induce MS-like inflammatory demyelinating plaques and suggest that MS may be a disease with heterogeneous pathogenetic mechanisms. From a large pathology sample of MS, collected in three international centers, we selected 51 biopsies and 32 autopsies that contained actively demyelinating lesions defined by stringent criteria. The pathology of the lesions was analyzed using a broad spectrum of immunological and neurobiological markers. Four fundamentally different patterns of demyelination were found, defined on the basis of myelin protein loss, the geography and extension of plaques, the patterns of oligodendrocyte destruction, and the immunopathological evidence of complement activation. Two patterns (I and II) showed close similarities to T-cell-mediated or T-cell plus antibody-mediated autoimmune encephalomyelitis, respectively. The other patterns (III and IV) were highly suggestive of a primary oligodendrocyte dystrophy, reminiscent of virus- or toxin-induced demyelination rather than autoimmunity. At a given time point of the disease--as reflected in autopsy cases--the patterns of demyelination were heterogeneous between p…

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Metadata

Authors
Lucchinetti, C., Br�ck, W., Parisi, J., Scheithauer, B., Rodriguez, M., & Lassmann, H.
Venue
Annals of Neurology
Publisher
Wiley
Published
2000-06
Volume
47
Issue
6
Pages
707-717
ISSN
  • 0364-5134
  • 1531-8249
DOI
10.1002/1531-8249(200006)47:6%3c707::aid-ana3%3e3.0.co;2-q
References
0
Language
en
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 5570 d)

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CoChat. (2026). Citation check: Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination. https://app.cochat.ai/papers/10.1002/1531-8249(200006)47:6%253c707::aid-ana3%253e3.0.co;2-q
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Lucchinetti, C., Br�ck, W., Parisi, J., Scheithauer, B., Rodriguez, M., & Lassmann, H. (2000). Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination. Annals of Neurology. https://doi.org/10.1002/1531-8249(200006)47%3A6%253c707%3A%3Aaid-ana3%253e3.0.co%3B2-q