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

  title={Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination},
  author={Claudia F. Lucchinetti and Wolfgang Br{\"u}ck and Joseph E. Parisi and Bernd Scheithauer and Moses Rodriguez and Hans Lassmann},
  journal={Annals of Neurology},
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. [] Key Method 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.

Clinical implications of neuropathological findings in multiple sclerosis

  • W. Brück
  • Biology, Medicine
    Journal of Neurology
  • 2005
The pathology and pathogenesis of lesions suggest the need for a subtype-specific treatment for multiple sclerosis, which may be possible when observations from pathology can be acted upon in the living MS patient.

Pathology of Multiple Sclerosis: Where Do We Stand?

The importance of developing imaging techniques able to capture early inflammatory cortical demyelination in MS is stressed in order to better understand the disease pathogenesis and to determine the impact of potential disease-modifying therapies on the cortex.

Pathological heterogeneity of idiopathic central nervous system inflammatory demyelinating disorders.

  • C. Lucchinetti
  • Medicine
    Current topics in microbiology and immunology
  • 2008
The last decade has seen a resurgence of interest in MS neuropathology. This resurgence was partly fueled by the development of new molecular and histochemical tools to examine the MS lesion

MS: is it one disease?

Findings would suggest that the heterogeneous features observed in active MS lesions sampled at different time-points are a reflection of the evolution of a single pathophysiological process, perhaps modified in part by genetic factors in individual cases.

Neuropathology of multiple sclerosis—new concepts

Recent neuropathological findings in MS—implications for diagnosis and therapy

Since the pathogenetic pathways of demyelination and tissue damage vary between different MS patients, their identification by paraclinical markers is of critical importance for diagnosis and therapeutic management.

Lessons from the neuropathology of atypical forms of multiple sclerosis

Atypical MS forms may help to elucidate pathogenic mechanisms in MS, and Devic’s neuromyelitis optica may represent the prototypical disease with antibody/complement-mediated demyelination, whereas cases with Balò's concentric sclerosis show oligodendrocyte dystrophy.

The spectrum of multiple sclerosis: new lessons from pathology

Purpose of reviewThis review will focus on recent developments in multiple sclerosis (MS) pathology with particular emphasis on the patterns and mediators of lesion formation in MS, the mechanisms of



Distinct Patterns of Multiple Sclerosis Pathology Indicates Heterogeneity in Pathogenesis

A new classification scheme of lesional activity on the basis of the molecular composition of myelin degradation products in macrophages is presented and it is indicated, that the demyelinated plaques of multiple sclerosis may reflect a common pathological end point of a variety of different immunological mechanisms ofMyelin destruction in this disease.

The application of multifactorial cluster analysis in the staging of plaques in early multiple sclerosis. Identification and characterization of the primary demyelinating lesion.

The results emphasize the need for lesion staging when multiple sclerosis tissues are being used in the investigation of pathogenic mechanisms, and suggest that further analysis of the oligoclonal B-cell response may be productive in the search for primary provoking antigens.

Natural history of multiple sclerosis.

Indictment of the microglia as the villain in multiple sclerosis

This work proposes a model of CNS demyelination that is not predicated upon the continued presence of autoreactive T cells and suggests that microglial activation is a central element in CNS demYelination and that the oligodendrocyte-myelin unit is the target.

A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex

A two-stage, multi-analytical genomic screen to identify genomic regions potentially harbouring MS susceptibility genes suggested that a multifactorial aetiology, including both environmental and multiple genetic factors of moderate effect, is more likely than a simple mendelian disease gene(s).

Autoimmunity to Myelin Oligodendrocyte Glycoprotein in Rats Mimics the Spectrum of Multiple Sclerosis Pathology

A new model of myelin oligodendrocyte glycoprotein (MOG) induced autoimmune encephalomyelitis became available, which, in a very standardized and predictable way, leads to chronic (relapsing or progressive) disease and widespread CNS demyelination.

Multiple sclerosis: In situ evidence for antibody‐ and complement‐mediated demyelination

A case of multiple sclerosis characterized by deposition of immunoglobulin and complement in the areas of active demyelination and degradation products that were immunoreactive for myelin antigens, Immunoglobulins, and C9neo antigen were described.

Monocyte/macrophage differentiation in early multiple sclerosis lesions

Findings indicate a differentiated pattern of macrophage activation in MS lesions and allow the staging of demyelinating lesions in routinely fixed and paraffin‐embedded tissue.

Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions.

Results indicate that LT and TNF may be involved in the immunopathogenesis of MS, and can be detected in both inflammatory cells and cells endogenous to the CNS.