Journal ArticleDOI
An updated histological classification system for multiple sclerosis lesions
TLDR
A simple and unifying classification of MS lesions incorporating many elements of earlier histological systems is proposed 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.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.read more
Citations
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Journal ArticleDOI
Microglia in neurodegeneration.
TL;DR: The immune checkpoints that control microglial functions are considered and how their imbalance and subsequent neuroinflammation leads to neurodegeneration is discussed.
Journal ArticleDOI
Pathogenic Mechanisms Associated With Different Clinical Courses of Multiple Sclerosis.
TL;DR: It is suggested that in MS patients two types of inflammation occur, which develop in parallel but partially independent from each other, and that CD8+ T-lymphocytes remain in the brain and spinal cord as tissue resident cells, which may focally propagate neuroinflammation when they re-encounter their cognate antigen.
Journal ArticleDOI
The compartmentalized inflammatory response in the multiple sclerosis brain is composed of tissue-resident CD8+ T lymphocytes and B cells
Joana Machado-Santos,Etsuji Saji,Anna R. Tröscher,Manuela Paunovic,Roland S. Liblau,Galina Gabriely,Christian G. Bien,Jan Bauer,Hans Lassmann +8 more
TL;DR: It is reported that chronic inflammation is dominated by tissue resident CD8+ T-cells and CD20+ B-cells, which are activated in lesions with demyelinating or neurodegenerative activity.
Journal ArticleDOI
Caspase-1 inhibition prevents glial inflammasome activation and pyroptosis in models of multiple sclerosis
Brienne A. McKenzie,Manmeet K. Mamik,Leina B. Saito,Roobina Boghozian,Roobina Boghozian,Maria Chiara Monaco,Eugene O. Major,Jian-Qiang Lu,William G. Branton,Christopher Power +9 more
TL;DR: Molecular evidence is reported for GSDMD-mediated inflammasome activation and pyroptosis in both myeloid cells and myelin-forming oligodendrocytes in the CNS of patients with MS and in the MS animal model, experimental autoimmune encephalomyelitis (EAE).
Journal ArticleDOI
Myelin in the Central Nervous System: Structure, Function, and Pathology.
TL;DR: The biology of myelin, the expanded relationship of myelinating oligodendrocytes with its underlying axons and the neighboring cells, and its disturbances in various diseases such as multiple sclerosis, acute disseminated encephalomyelitis, and neuromyELitis optica spectrum disorders are reviewed.
References
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Journal ArticleDOI
Axonal transection in the lesions of multiple sclerosis.
TL;DR: Transected axons are common in the lesions of multiple sclerosis, and axonal transection may be the pathologic correlate of the irreversible neurologic impairment in this disease.
Journal ArticleDOI
Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination.
Claudia F. Lucchinetti,Wolfgang Brück,Joseph E. Parisi,Bernd W. Scheithauer,Moses Rodriguez,Hans Lassmann +5 more
TL;DR: At a given time point of the disease, the patterns of demyelination were heterogeneous between patients, but were homogenous within multiple active lesions from the same patient, suggesting that MS may be a disease with heterogeneous pathogenetic mechanisms.
Journal ArticleDOI
Identification of a unique TGF-β–dependent molecular and functional signature in microglia
Oleg Butovsky,Mark P. Jedrychowski,Craig S. Moore,Ron Cialic,Amanda J. Lanser,Galina Gabriely,Thomas Koeglsperger,Ben Dake,Pauline M. Wu,Camille Doykan,Zain Fanek,LiPing Liu,Zhuoxun Chen,Jeffrey D. Rothstein,Richard M. Ransohoff,Steven P. Gygi,Jack P. Antel,Howard L. Weiner +17 more
TL;DR: It is found that TGF-β was required for the in vitro development of microglia that express the microglial molecular signature characteristic of adultmicroglia and that microglian were absent in the CNS of TGF -β1–deficient mice.
Journal ArticleDOI
Cortical demyelination and diffuse white matter injury in multiple sclerosis
Alexandra Kutzelnigg,Claudia F. Lucchinetti,Christine Stadelmann,Wolfgang Brück,Helmut Rauschka,Markus Bergmann,Manfred Schmidbauer,Joseph E. Parisi,Hans Lassmann +8 more
TL;DR: Global brain pathology in multiple sclerosis is analysed, focusing on the normal-appearing white matter (NAWM) and the cortex, to suggest that multiple sclerosis starts as a focal inflammatory disease of the CNS, which gives rise to circumscribed demyelinated plaques in the white matter.
Journal ArticleDOI
Immunopathology of multiple sclerosis
TL;DR: The current understanding of multiple sclerosis immunopathology is discussed, long-standing hypotheses regarding the role of the immune system in the disease are evaluated, and key questions that are still unanswered are delineated.
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