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Cited by 692Multiple Sclerosis Research StudiesNeuroinflammation and Neurodegeneration MechanismsPeripheral Neuropathies and Disorders

The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.

An updated histological classification system for multiple sclerosis lesions

Kuhlmann, Tanja, Ludwin, Samuel, Prat, Alexandre, Antel, Jack, Brück, Wolfgang, Lassmann, Hans·2017·Acta Neuropathologica
DOI 10.1007/s00401-016-1653-y
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Abstract

Multiple sclerosis is a complex and heterogeneous, most likely autoimmune, demyelinating disease of the central nervous system (CNS). Although a number of histological classification systems for CNS lesions have been used by different groups in recent years, no uniform classification exists. In this paper, we propose a simple and unifying classification of MS lesions incorporating many elements of earlier histological systems that aims to provide guidelines for neuropathologists and researchers studying MS lesions to allow for better comparison of different studies performed with MS tissue, and to aid in understanding the pathogenesis of the disease. Based on the presence/absence and distribution of macrophages/microglia (inflammatory activity) and the presence/absence of ongoing demyelination (demyelinating activity), we suggest differentiating between active, mixed active/inactive, and inactive lesions with or without ongoing demyelination. Active lesions are characterized by macrophages/microglia throughout the lesion area, whereas mixed active/inactive lesions have a hypocellular lesion center with macrophages/microglia limited to the lesion border. Inactive lesions are almost completely lacking macrophages/microglia. Active and mixed active/inactive lesions can be further subdivided into lesions with ongoing myelin destruction (demyelinating lesions) and lesions in which the destruction of myelin has ceased, but macrophages are still present (post-demyelinating lesions). This distinction is based on the presence or absence of myelin degradation products within the cytoplasm of macrophages/microglia. For this classification of MS lesions, identification of myelin with histological stains [such as luxol fast blue-PAS] or by immunohistochemistry using antibodies against myelin basic-protein (MBP) or proteolipid-protein (PLP), as well as, detection of macrophages/microglia by, e.g., anti-CD68 is sufficient. Active and demyelinating lesions may be further subdivided into the early and late demyelinating lesions. The former is defined by the presence in macrophages of major and small molecular weight myelin proteins, such as cyclic nucleotide diphosphoesterase (CNP), myelin oligodendrocyte glycoprotein (MOG), or myelin-associated protein (MAG), whereas macrophages in the latter demonstrate merely the presence of the major myelin proteins MBP or PLP. We discuss the histological features and staining techniques required to classify MS lesions, and, in addition, describe the histological hallmarks of cortical pathology and diffuse white matter changes, as well as of remyelination.

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Research works printed but not linked: 1

  1. Prineas JW (1985) The neuropathology of multiple sclerosis. In: Koetsier JC (ed) Demyelinating Diseases. Elsevier Science Publishers, Amsterdam, pp 213–257

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Metadata

Authors
Kuhlmann, T., Ludwin, S., Prat, A., Antel, J., Brück, W., & Lassmann, H.
Affiliations
  • University Hospital Münster (DE)
  • Montreal Neurological Institute and Hospital (CA)
  • Centre Hospitalier de l’Université de Montréal (CA)
  • Universitätsmedizin Göttingen (DE)
  • Medical University of Vienna (AT)
Corresponding author
Kuhlmann, Tanja
ORCID
Venue
Acta Neuropathologica
Publisher
Springer Science and Business Media LLC
Published
2016-12-17
Volume
133
Issue
1
Pages
13-24
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
DOI
10.1007/s00401-016-1653-y
OpenAlex
W2562977489
Cited by
692
References
59
Citations by year
2026: 58 · 2025: 87 · 2024: 113 · 2023: 81 · 2022: 99 · 2021: 83 · 2020: 59 · 2019: 51 · 2018: 42 · 2017: 17
FWCI
33.28
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (unspecified)
Locations
  • Acta Neuropathologica (publishedVersion)
  • PubMed (publishedVersion)
  • GRO (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (SFB-TRR128 B-7, Ku1477/6-1)
  • IZKF (KuT3/012/15)
  • Austrian Science Fund (FWF Project I 2114-B27)
  • CIHR; Quebec, FRQS
  • CIHR, Quebec, FRQS
  • BMBF, KKNMS
Topics
  • Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Clinical Neurology › Peripheral Neuropathies and Disorders
Keywords
multiple sclerosis, histological classification, demyelination, macrophages, microglia, active lesions, myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein, myelin-associated glycoprotein, cortical pathology, remyelination, demyelinating disease, central nervous system lesions, neuropathology
MeSH terms
Animals, Humans, Macrophages, Multiple Sclerosis, Microglia, White Matter

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