title: Grey matter atrophy is associated with disability increase in natalizumab-treated patients.
abstract: BACKGROUND
  Brain volume loss (BVL) is a key outcome in multiple sclerosis (MS) trials. Natalizumab is highly effective on inflammation with moderate impact on atrophy.
  
  
  OBJECTIVE
  To explore BVL in patients receiving natalizumab with an emphasis on grey matter (GM).
  
  
  METHODS
  We performed a retrospective post hoc analysis of BVL in 38 patients receiving natalizumab for 3 years using longitudinal voxel-based morphometry (VBM) and FreeSurfer.
  
  
  RESULTS
  Significant BVL was observed during first year: brain parenchymal fraction (BPF): -1.12% ( p < 0.001); white matter fraction (WMF): -0.9% ( p = 0.001); grey matter fraction (GMF): -1.28% ( p = 0.002). GM loss was found using VBM in bilateral cerebellum, cingulum, left > right fronto-parietal cortex, right > left hippocampus and left caudate. FreeSurfer showed significant volume losses in subcortical GM, brainstem and cerebellum, and cortical thinning in the left insula. In the second year, only WMF decrease (-0.6%; p = 0.015) was observed with no VBM changes, although FreeSurfer detected significant volume loss in thalamus, hippocampus and cerebellum. Baseline gadolinium enhancement influenced WMF and BPF changes during the first year, but not GMF. Patients with confirmed Expanded Disability Status Scale (EDSS) worsening at 3 years had lower baseline GMF and left thalamus volume and greater BVL over follow-up.
  
  
  CONCLUSIONS
  BVL develops mainly during the first year of natalizumab therapy. GM changes are independent of baseline inflammation and correlate with disability.
authors.affiliation: Servei de Neurologia/Neuroimmunologia, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Ethel
authors.initials: E
authors.lastname: Ciampi
authors.affiliation: Servei de Radiologia, Unitat de Ressonància Magnètica, Institut de Diagnòstic per la Imatge (IDI), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Deborah
authors.initials: D
authors.lastname: Pareto
authors.affiliation: Servei de Neurologia/Neuroimmunologia, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Sastre-Garriga
authors.affiliation: Servei de Neurologia/Neuroimmunologia, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Vidal-Jordana
authors.affiliation: Servei de Neurologia/Neuroimmunologia, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Tur
authors.affiliation: Servei de Neurologia/Neuroimmunologia, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Río
authors.affiliation: Servei de Neurologia/Neuroimmunologia, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Tintoré
authors.affiliation: Servei de Radiologia, Unitat de Ressonància Magnètica, Institut de Diagnòstic per la Imatge (IDI), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Auger
authors.affiliation: Servei de Radiologia, Unitat de Ressonància Magnètica, Institut de Diagnòstic per la Imatge (IDI), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Alex
authors.initials: A
authors.lastname: Rovira
authors.affiliation: Servei de Neurologia/Neuroimmunologia, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
mesh_terms: D000328:Adult; D001284:Atrophy; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D066128:Gray Matter / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology*; D000069442:Natalizumab / Q000627:therapeutic use*; D012189:Retrospective Studies; D066127:White Matter / Q000187:drug effects / Q000473:pathology; D055815:Young Adult
chemical_list: D000069442:Natalizumab
keywords: Multiple sclerosis; brain atrophy; disability; grey matter; natalizumab