title: Astrocytic damage is far more severe than demyelination in NMO: a clinical CSF biomarker study.
abstract: BACKGROUND
  Loss of aquaporin 4 and glial fibrillary acidic protein (GFAP) with necrosis and demyelination is a prominent pathologic feature of neuromyelitis optica (NMO). However, the clinicopathologic significance of astrocytic damage and its relation with demyelination are unknown.
  
  
  OBJECTIVE
  To analyze clinical and pathologic values of a CSF biomarker of astrocytic damage in NMO.
  
  
  METHODS
  We measured the levels of GFAP, S100B, myelin basic protein (MBP), and neurofilament H (NF-H) in CSF obtained from patients with NMO (n = 33), multiple sclerosis (MS) (n = 27), acute disseminated encephalomyelitis (ADEM), ischemia, meningitis, and other neurologic disease controls (OND).
  
  
  RESULTS
  The CSF-GFAP levels during relapse in NMO (2,476.6 +/- 8,815.0 ng/mL) were significantly higher than those in MS (0.8 +/- 0.4 ng/mL) and OND (0.7 +/- 0.5 ng/mL), and much beyond those in ADEM (14.1 +/- 27.4 ng/mL). The sensitivity and specificity of CSF-GFAP for NMO was 90.9% and 76.9% in all, but the specificity improved above 90% in cases limited to demyelinating diseases. CSF-S100B showed a similar trend but was less remarkable. In contrast, MBP and NF-H are not different between NMO and MS. Following treatments, the CSF-GFAP rapidly decreased to a normal level, but CSF-MBP remained high. There were strong correlations between the CSF-GFAP, CSF-S100B, or CSF-MBP levels and Expanded Disability Status Scale (EDSS) or spinal lesion length in the acute phase (r > 0.6). Only CSF-GFAP correlated with EDSS at 6-month follow-up (r = 0.51) in NMO.
  
  
  CONCLUSIONS
  Astrocytic damage reflected by elevated CSF glial fibrillary acidic protein is a clinically relevant, primary pathologic process in neuromyelitis optica, and is far more severe than demyelination.
authors.affiliation: Department of Neurology, Tohoku University Graduate School of Medicine, Aobaku, Sendai, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Takano
authors.forename: T
authors.initials: T
authors.lastname: Misu
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Fujihara
authors.forename: Y
authors.initials: Y
authors.lastname: Itoyama
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D051401:Aquaporin 4 / Q000276:immunology; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology*; D003711:Demyelinating Diseases / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy; D004185:Disability Evaluation; D004673:Encephalomyelitis, Acute Disseminated / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005904:Glial Fibrillary Acidic Protein / Q000097:blood* / Q000134:cerebrospinal fluid*; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000473:pathology; D004676:Myelin Basic Protein / Q000134:cerebrospinal fluid; D009414:Nerve Growth Factors / Q000134:cerebrospinal fluid; D009422:Nervous System Diseases / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000473:pathology; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid; D009471:Neuromyelitis Optica / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000473:pathology*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000134:cerebrospinal fluid; D018709:Statistics, Nonparametric
chemical_list: D000906:Antibodies; D051401:Aquaporin 4; D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D009414:Nerve Growth Factors; D016900:Neurofilament Proteins; D018696:Neuroprotective Agents; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C051774:neurofilament protein H; D008775:Methylprednisolone