title: Pathology of multiple sclerosis: where do we stand?
abstract: OBJECTIVE
  This article summarizes the pathologic features of multiple sclerosis (MS) and other inflammatory demyelinating diseases and discusses neuropathologic studies that have yielded novel insights into potential mechanisms of demyelination.
  
  
  RESULTS
  The pathologic hallmark of MS consists of focal demyelinated plaques within the CNS, with variable degrees of inflammation, gliosis, and neurodegeneration. Active MS lesions show a profound pathologic heterogeneity with four major patterns of immunopathology, suggesting that the targets of injury and mechanisms of demyelination in MS may be different in different disease subgroups. Recent pathologic studies have suggested that the subarachnoid space and cortex may be initial sites and targets of the MS disease process, that inflammatory cortical demyelination is present early in MS, and that meningeal inflammation may drive cortical and white matter injury in some MS patients.
  
  
  CONCLUSIONS
  MS is heterogeneous with respect to clinical, genetic, radiographic, and pathologic features; surrogate MRI, clinical, genetic, serologic, and/or CSF markers for each of the four immunopatterns need to be developed in order to recognize them in the general nonbiopsied MS population. Inflammatory cortical demyelination is an important early event in the pathogenesis of MS and may be driven by meningeal inflammation. These observations stress the importance of developing imaging techniques able to capture early inflammatory cortical demyelination in order to better understand the disease pathogenesis and to determine the impact of potential disease-modifying therapies on the cortex.
authors.affiliation: Department of Neurology, Mayo Clinic College of Medicine, 200 First St Southwest, Rochester, MN 55905, USA.
authors.forename: Bogdan F Gh
authors.initials: BF
authors.lastname: Popescu
authors.forename: Istvan
authors.initials: I
authors.lastname: Pirko
authors.forename: Claudia F
authors.initials: CF
authors.lastname: Lucchinetti
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000473:pathology; D002908:Chronic Disease; D003711:Demyelinating Diseases / Q000473:pathology; D004673:Encephalomyelitis, Acute Disseminated / Q000473:pathology; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D004684:Leukoencephalitis, Acute Hemorrhagic / Q000473:pathology; D056784:Leukoencephalopathies / Q000473:pathology; D008581:Meningitis / Q000473:pathology; D009103:Multiple Sclerosis / Q000209:etiology / Q000473:pathology*; D009471:Neuromyelitis Optica / Q000473:pathology; D055815:Young Adult
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