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

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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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Background
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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: Kuhlmann, Tanja
Prat, Alexandre
Antel, Jack
Brück, Wolfgang
Lassmann, Hans
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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An updated histological classification system for multiple sclerosis lesions

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