The changing concepts in the neuropathology of acquired demyelinating central nervous system disorders

  title={The changing concepts in the neuropathology of acquired demyelinating central nervous system disorders},
  author={Hans Lassmann},
  journal={Current Opinion in Neurology},
  • H. Lassmann
  • Published 1 June 2019
  • Biology, Medicine
  • Current Opinion in Neurology
Purpose of review Research on multiple sclerosis (MS) pathogenesis and therapy is to a large extent driven by results obtained in experimental autoimmune encephalomyelitis (EAE). This approach provided deep insights into the mechanism of brain inflammation and immune mediated tissue injury and, thus, most of our currently established therapies for MS patients have been developed with profound contributions of experimental autoimmune research. Recent data, which are summarized in this review… 
MOG-antibody-associated disease is different from MS and NMOSD and should be classified as a distinct disease entity – Commentary
Research groups across the globe have detected MOG-antibody by CBA in patients with optic neuritis, acute/multiphasic disseminated encephalomyelitis, myelitis and other encephalitides while typical MS cases are largely Mog-antIBody-negative.
Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination
Investigation of the epitope, binding sensitivity, and affinity of MOG Ab in a cohort of 139 and 148 MOG antibody-seropositive children and adults finds adults with a relapsing course intrinsically presented with a reduced immunoreactivity to Proline42 and had a more diverse Mog Ab response, a feature that may be harnessed for predicting relapse.
Visual Dysfunction in Multiple Sclerosis and its Animal Model, Experimental Autoimmune Encephalomyelitis: a Review.
Additional routes, including pro-inflammatory mediator-filled choroidal and subarachnoid spaces, are discussed with respect to their roles in EAE-induced visual disability and as analogues of MS in humans.
Fundamental mechanistic insights from rare but paradigmatic neuroimmunological diseases
Key mechanistic insights into three rare but paradigmatic neuroimmunological diseases — Susac syndrome, Rasmussen encephalitis and narcolepsy type 1 — are summarized and how next-generation technologies and refined animal models can further improve the understanding of pathomechanisms are outlined, thereby paving the way for the development of targeted therapeutic approaches.
Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Therapeutic Use in Central Nervous System Demyelinating Disorders
The potential of cell-free therapeutics utilizing MSC secretome-derived extracellular vesicles—and in particular exosomes—in the treatment of autoimmune demyelinating diseases is discussed, and an outlook for studies of their future applications is provided.
MOG-antibody-associated disease is different from MS and NMO and should be considered as a distinct disease entity – No
Although several criteria have been proposed to define the disease, a sine qua non rule has been kept as the main essence of MS: central nervous system inflammatory demyelination with dissemination in time and space.
miR-20a suppresses Treg differentiation by targeting Map3k9 in experimental autoimmune encephalomyelitis
Background Experimental autoimmune encephalomyelitis (EAE) is a model for inflammatory demyelinating diseases of the central nervous system (CNS), a group of autoimmune diseases characterized by
Mannan-MOG35-55 Reverses Experimental Autoimmune Encephalomyelitis, Inducing a Peripheral Type 2 Myeloid Response, Reducing CNS Inflammation, and Preserving Axons in Spinal Cord Lesions
The results show that OM-MOG treats MOG-EAE in a peptide-specific manner, across mouse/human MHC class II barriers, through induction of a peripheral type 2 myeloid cell response and T cell anergy, and suggest thatOM-peptides might be useful for suppressing antigen-specific CD4+ T cell responses in the context of human autoimmune CNS demyelination.
Metabolic determinants of leukocyte pathogenicity in neurological diseases
The role of intracellular metabolic cues in regulating leukocyte‐mediated CNS damage in Alzheimer's and Parkinson's disease, multiple sclerosis and stroke is discussed, highlighting the therapeutic potential of drugs targeting metabolic pathways for the treatment of neurological diseases.


Multiple sclerosis: experimental models and reality
One of the most frequent statements, provided in different variations in the introduction of experimental studies on multiple sclerosis (MS), is that “Multiple sclerosis is a demyelinating autoimmune
Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination
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.
Defining distinct features of anti-MOG antibody associated central nervous system demyelination
It is proposed that MOG+ CNS demyelinating disease represents a distinct novel disease entity and mechanistic insight is provided on how this peripheral anti-MOG ab response may be of pathogenetic relevance in triggering acute flares of inflammatory CNS Demyelination.
A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica.
The extent of complement activation, eosinophilic infiltration and vascular fibrosis observed in the Devic NMO cases is more prominent compared with that in prototypic multiple sclerosis, and supports a role for humoral immunity in the pathogenesis of NMO.
Deciphering the Role of B Cells in Multiple Sclerosis—Towards Specific Targeting of Pathogenic Function
The current knowledge on the role of B cells, plasma cells and antibodies in MS is summarized and how approved and future treatments, first and foremost anti-CD20 antibodies, therapeutically modify these B cell components are elucidated.
Human antibodies against the myelin oligodendrocyte glycoprotein can cause complement-dependent demyelination
This study shows that a subset of human MOG antibodies can induce complement-dependent pathogenic effects in a murine ex vivo animal model, and a high titer of species-specific MOG antibody-mediated pathology in animal models may be critical for demyelinating effects in mouse and rat animal models.
Histopathology and clinical course of MOG-antibody-associated encephalomyelitis
This case contributes a new, so far missing link in the emerging spectrum of MOG‐antibody‐associated encephalomyelitis and antibodies against myelin oligodendrocyte glycoprotein (MOG).
ADEM-like presentation, anti-MOG antibodies, and MS pathology: TWO case reports
A subgroup of adult patients negative for aquaporin-4 antibody fulfilling diagnostic clinical and radiologic criteria for neuromyelitis optica spectrum disorder (NMOSD) harbor high-titer serum MOG-abs.
Fulminant demyelinating encephalomyelitis
Objectives: Antibodies to myelin oligodendrocyte glycoprotein (MOG) are detectable in inflammatory demyelinating CNS diseases, and MOG antibody–associated diseases seem to have a better prognosis