title: Early brain pseudoatrophy while on natalizumab therapy is due to white matter volume changes.
abstract: BACKGROUND
  Investigation of atrophy data from a pivotal natalizumab trial has demonstrated an increased rate of volume loss, compared to placebo, after the first year of therapy. It was considered to be probably due to a pseudoatrophy effect.
  
  
  OBJECTIVE
  To assess grey and white matter volume changes and their relation to global brain volume changes and to baseline inflammation, for patients under natalizumab therapy.
  
  
  METHODS
  We selected 45 patients on natalizumab therapy for at least 24 months, with magnetic resonance imaging (MRI) scans at baseline, 12 and 24 months. We calculated the percentage brain volume change (PBVC) for the first and second year, using SIENA software. Grey and white matter fractions (GMF and WMF, respectively) for the first year were calculated with SPM5, using lesion masks. After quality checks, six patients were excluded. We studied the predictive variables of change in brain volumes.
  
  
  RESULTS
  The PBVC decrease was faster during the first year (-1.10% ± 1.43%), as compared to the second (-0.51% ± 0.96%) (p = 0.037). These differences were more marked in patients with baseline gadolinium-enhancing lesions (p = 0.005). Mean GMF and WMF changes during the first year of treatment were +1.15% (n.s.) and -1.72% (p = 0.017), respectively. The presence of active lesions at baseline MRI predicted PBVC (p = 0.022) and WMF change (p = 0.026) during the first year of treatment, after adjusting for age and corticosteroid treatment. No predictors were found for GMF volume changes.
  
  
  CONCLUSIONS
  Early brain volume loss during natalizumab therapy is mainly due to WMF volume loss and it is related to the inflammatory activity present at the onset of therapy. We found that the pseudoatrophy effect is mostly due to white matter volume changes.
authors: Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain.
authors: Angela
authors: A
authors: Vidal-Jordana
authors: Jaume
authors: J
authors: Sastre-Garriga
authors: Francisco
authors: F
authors: Pérez-Miralles
authors: Carmen
authors: C
authors: Tur
authors: Mar
authors: M
authors: Tintoré
authors: Alejandro
authors: A
authors: Horga
authors: Cristina
authors: C
authors: Auger
authors: Jordi
authors: J
authors: Río
authors: Carlos
authors: C
authors: Nos
authors: Mari C
authors: MC
authors: Edo
authors: María J
authors: MJ
authors: Arévalo
authors: Joaquín
authors: J
authors: Castilló
authors: Alex
authors: A
authors: Rovira
authors: Xavier
authors: X
authors: Montalban
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology*; D000069442:Natalizumab; D009413:Nerve Fibers, Myelinated / Q000473:pathology*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab
keywords: Multiple sclerosis; brain MRI; brain atrophy; brain volume; drug side effects; monoclonal antibody therapy; natalizumab; pseudoatrophy; white matter