title: Cognitive impairment and cortical degeneration in neuromyelitis optica.
abstract: OBJECTIVE
  Neuromyelitis optica spectrum disorder (NMOsd) is an inflammatory and demyelinating syndrome characterized by optic neuritis and myelitis. Several magnetization transfer magnetic resonance imaging (MRI) studies have revealed abnormalities in normal-appearing gray matter in NMOsd. The aim of this study is to elucidate the characteristics and pathogenesis of cognitive impairment and neurodegeneration in NMOsd brains.
  
  
  METHODS
  Fourteen Japanese patients with serologically verified NMOsd, 17 patients with multiple sclerosis (MS), and 37 healthy controls were assessed with the Rao's Brief Repeatable Battery of Neuropsychological Tests (BRBN). Using 128 tissue blocks from 6 other cases of NMOsd, 3 cases of MS, and 4 controls without central nervous system involvement, we performed quantitative analysis of cortical neuronal loss and layer-specific changes in NMOsd.
  
  
  RESULTS
  In BRBN assessments, 57% of NMOsd patients and 47% of MS patients had impaired performance on at least 3 cognitive tests. Cognitive impairment in NMOsd was common even in the limited form of disease, indicating that NMOsd may progress insidiously from early stages of disease. Neuropathological assessments showed neuronal loss in cortical layers II, III, and IV, with nonlytic reaction of aquaporin-4 (AQP4)-negative astrocytes in layer I, massive activated microglia in layer II, and meningeal inflammation in NMOsd brains. All NMO cases showed no evidence of cortical demyelination.
  
  
  CONCLUSIONS
  We demonstrate cognitive impairment and substantial cortical neuronal loss with unique AQP4 dynamics in astrocytes in NMOsd. These data indicate pathological processes consisting not only of inflammatory demyelinating events characterized by pattern-specific loss of AQP4 immunoreactivity but also cortical neurodegeneration in NMOsd brains.
authors: Department of Neurology, Niigata University, Japan.
authors: Etsuji
authors: E
authors: Saji
authors: Musashi
authors: M
authors: Arakawa
authors: Kaori
authors: K
authors: Yanagawa
authors: Yasuko
authors: Y
authors: Toyoshima
authors: Akiko
authors: A
authors: Yokoseki
authors: Kouichirou
authors: K
authors: Okamoto
authors: Mika
authors: M
authors: Otsuki
authors: Kohei
authors: K
authors: Akazawa
authors: Akiyoshi
authors: A
authors: Kakita
authors: Hitoshi
authors: H
authors: Takahashi
authors: Masatoyo
authors: M
authors: Nishizawa
authors: Izumi
authors: I
authors: Kawachi
mesh_terms: D051401:Aquaporin 4 / Q000235:genetics*; D044466:Asian People / Q000235:genetics / Q000523:psychology; D001253:Astrocytes / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D006801:Humans; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D009471:Neuromyelitis Optica / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4