title: Neuromyelitis optica lesions may inform multiple sclerosis heterogeneity debate.
abstract: OBJECTIVE
  Neuromyelitis optica (NMO) and multiple sclerosis (MS) are considered inflammatory demyelinating diseases with distinguishing pathological characteristics. NMO pathology shows perivascular immunoglobulin G and complement deposition, as well as an astrocytopathy with aquaporin-4 (AQP4) loss. MS lesions reveal a profound, interindividual heterogeneity in immunopathological patterns of active demyelination, which has been challenged by the description of stage-dependent sequences of pathological features. The aim of our study was to compare the histological characteristics of early active demyelinating NMO and MS brain lesions.
  
  
  METHODS
  Thirteen cases with supraspinal active demyelinating NMO lesions were analyzed using immunohistochemistry. Results were compared with the published characteristics of MS lesions.
  
  
  RESULTS
  A subset of supraspinal lesions from AQP4-IgG-seropositive NMO patients revealed both (1) complement activation products within macrophages at sites of active demyelination and (2) oligodendrocyte apoptosis and a preferential loss of myelin-associated glycoprotein. These characteristics resemble features previously associated with MS lesion patterns II and III, and were present in addition to characteristic histopathological NMO features, namely loss of AQP4 and astrocytes.
  
  
  CONCLUSIONS
  Early active demyelinating NMO lesions may show complement within macrophages and oligodendrocyte apoptosis associated with a selective loss of minor myelin proteins, in addition to typical NMO features. We hypothesize these findings occur simultaneously only in a subset of active demyelinating NMO lesions. These observations plausibly explain the findings of Barnett and Prineas and further support the concept of interindividual heterogeneity in MS.
authors.affiliation: Department of Neuropathology, University Medical Center, Georg August University, Göttingen, Germany. wbrueck@med.uni-goettingen.de
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.forename: Bogdan
authors.initials: B
authors.lastname: Popescu
authors.forename: Claudia F
authors.initials: CF
authors.lastname: Lucchinetti
authors.forename: Silva
authors.initials: S
authors.lastname: Markovic-Plese
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.forename: Dietmar Rudolf
authors.initials: DR
authors.lastname: Thal
authors.forename: Imke
authors.initials: I
authors.lastname: Metz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D051401:Aquaporin 4 / Q000276:immunology / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D003167:Complement Activation / Q000502:physiology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D009471:Neuromyelitis Optica / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*
chemical_list: C496030:AQP4 protein, human; D016564:Amyloid beta-Protein Precursor; D051401:Aquaporin 4; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G