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

Claudia F Lucchinetti, Wolfgang Brück, Joseph E Parisi, Bernd Scheithauer, Moses Rodriguez, Hans Lassmann

Research output: Contribution to journalArticle

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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 patients, but were homogenous within multiple active lesions from the same patient. This pathogenetic heterogeneity of plaques from different MS patients may have fundamental implications for the diagnosis and therapy of this disease.

Original languageEnglish (US)
Pages (from-to)707-717
Number of pages11
JournalAnnals of Neurology
Volume47
Issue number6
DOIs
StatePublished - 2000

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Demyelinating Diseases
Multiple Sclerosis
Oligodendroglia
Autoimmunity
Autopsy
Pathology
Myelin Proteins
T-Lymphocytes
Encephalomyelitis
Geography
Complement Activation
Virus Diseases
Viruses
Biopsy
Antibodies
Therapeutics
Genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Heterogeneity of multiple sclerosis lesions : Implications for the pathogenesis of demyelination. / Lucchinetti, Claudia F; Brück, Wolfgang; Parisi, Joseph E; Scheithauer, Bernd; Rodriguez, Moses; Lassmann, Hans.

In: Annals of Neurology, Vol. 47, No. 6, 2000, p. 707-717.

Research output: Contribution to journalArticle

Lucchinetti, Claudia F ; Brück, Wolfgang ; Parisi, Joseph E ; Scheithauer, Bernd ; Rodriguez, Moses ; Lassmann, Hans. / Heterogeneity of multiple sclerosis lesions : Implications for the pathogenesis of demyelination. In: Annals of Neurology. 2000 ; Vol. 47, No. 6. pp. 707-717.
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