title: A longitudinal uncontrolled study of cerebral gray matter volume in patients receiving natalizumab for multiple sclerosis.
abstract: OBJECTIVE
  Brain atrophy in multiple sclerosis (MS) selectively affects gray matter (GM), which is highly relevant to disability and cognitive impairment. We assessed cerebral GM volume (GMV) during one year of natalizumab therapy.
  
  
  METHODS
  Patients with relapsing-remitting (n = 18) or progressive (n = 2) MS had MRI ∼1 year apart during natalizumab treatment. At baseline, patients were on natalizumab for (mean ± SD) 16.6 ± 10.9 months with age 38.5 ± 7.4 and disease duration 9.7 ± 4.3 years.
  
  
  RESULTS
  At baseline, GMV was 664.0 ± 56.4 ml, Expanded Disability Status Scale (EDSS) score was 2.3 ± 2.0, timed 25-foot walk (T25FW) was 6.1±3.4 s; two patients (10%) had gadolinium (Gd)-enhancing lesions. At follow-up, GMV was 663.9 ± 60.2 mL; EDSS was 2.6 ± 2.1 and T25FW was 5.9 ± 2.9 s. One patient had a mild clinical relapse during the observation period (0.052 annualized relapse rate for the entire cohort). No patients had Gd-enhancing lesions at follow-up. Linear mixed-effect models showed no significant change in annualized GMV [estimated mean change per year 0.338 mL, 95% confidence interval -9.66, 10.34, p = 0.94)], GM fraction (p = 0.92), whole brain parenchymal fraction (p = 0.64), T2 lesion load (p = 0.64), EDSS (p = 0.26) or T25FW (p = 0.79).
  
  
  CONCLUSIONS
  This pilot study shows no GM atrophy during one year of natalizumab MS therapy. We also did not detect any loss of whole brain volume or progression of cerebral T2 hyperintense lesion volume during the observation period. These MRI results paralleled the lack of clinical worsening.
authors.affiliation: a a Laboratory for Neuroimaging Research, Department of Neurology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School , Boston, MA , USA.
authors.forename: Fariha
authors.initials: F
authors.lastname: Khalid
authors.affiliation: a a Laboratory for Neuroimaging Research, Department of Neurology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School , Boston, MA , USA.
authors.forename: Shahamat
authors.initials: S
authors.lastname: Tauhid
authors.affiliation: a a Laboratory for Neuroimaging Research, Department of Neurology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School , Boston, MA , USA.
authors.forename: Alicia S
authors.initials: AS
authors.lastname: Chua
authors.affiliation: a a Laboratory for Neuroimaging Research, Department of Neurology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School , Boston, MA , USA.|c c Biostatistics Center, Massachusetts General Hospital, Harvard Medical School , Boston, MA , USA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Healy
authors.affiliation: a a Laboratory for Neuroimaging Research, Department of Neurology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School , Boston, MA , USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Stankiewicz
authors.affiliation: a a Laboratory for Neuroimaging Research, Department of Neurology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School , Boston, MA , USA.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
authors.affiliation: a a Laboratory for Neuroimaging Research, Department of Neurology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School , Boston, MA , USA.|b b Laboratory for Neuroimaging Research, Department of Radiology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School , Boston, MA , USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Bakshi
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D004185:Disability Evaluation; D005260:Female; D005500:Follow-Up Studies; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000187:drug effects*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D000069442:Natalizumab / Q000627:therapeutic use*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D000069442:Natalizumab
keywords: MRI; brain atrophy; gray matter; multiple sclerosis; natalizumab