Acta Neuropathologica

, Volume 133, Issue 1, pp 13–24 | Cite as

An updated histological classification system for multiple sclerosis lesions

  • Tanja Kuhlmann
  • Samuel Ludwin
  • Alexandre Prat
  • Jack Antel
  • Wolfgang Brück
  • Hans Lassmann
Consensus Paper


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.


Myelin Protein Active Lesion Wallerian Degeneration Myelin Oligodendrocyte Glycoprotein Normal Appear White Matter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This study was supported by Grants from the German Research Foundation (SFB-TR128-B7; Ku1477/6-1), the Interdisciplinary Clinical Research Center, Münster (IZKF; KuT3/012/15) to TK, the German Ministry for Education and Research (BMBF, ‘‘German Competence Network Multiple Sclerosis’’ (KKNMS) to WB, and the ERA-Net Neuron project MELTRA funded by the Austrian Science Fund (FWF, Project I 2114—B27) and CIHR, Quebec, FRQS to AP, and HL.


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© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Institute of NeuropathologyUniversity Hospital MünsterMünsterGermany
  2. 2.Department of Pathology and Molecular MedicineQueen’s UniversityKingstonCanada
  3. 3.Neuroimmunology Research LaboratoryCentre de Recherche DU Centre Hospitalier de l’Université de Montréal (CRCHUM)MontrealCanada
  4. 4.Neuroimmunology Unit, Montréal Neurological InstituteMcGill UniversityMontrealCanada
  5. 5.Department of NeuropathologyUniversity Medical Center, Georg August UniversityGöttingenGermany
  6. 6.Center for Brain ResearchMedical University of ViennaViennaAustria

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