title: Predictive value of early brain atrophy on response in patients treated with interferon β.
abstract: OBJECTIVE
  To investigate the association between brain volume loss during the first year of interferon treatment and clinical outcome at 4 years.
  
  
  METHODS
  Patients with multiple sclerosis initiating interferon β were clinically evaluated every 6 months for the presence of relapses and assessment of global disability using the Expanded Disability Status Scale (EDSS). MRI scans were performed at baseline and after 12 months, and the percentage of brain volume change (PBVC), brain parenchymal volume change (BPVc%), gray matter volume change (GMVc%), and white matter volume change (WMVc%) were estimated. Patients were divided based on the cutoff values for predicting confirmed EDSS worsening obtained by receiver operating characteristic analysis for all atrophy measurements. Survival curves and Cox proportional hazards regression to predict disability worsening at last observation were applied, adjusting for demographic, clinical, and radiologic variables.
  
  
  RESULTS
  Larger PBVC and WMVc% decreases were observed in patients with disability worsening at 4 years of follow-up, whereas no differences were found in BPVc% or GMVc%. Cutoff points were obtained for PBVC (-0.86%; sensitivity 65.5%, specificity 71.4%) and WMVc% (-2.49%; sensitivity 85.3%, specificity 43.8%). Patients with decreases of PBVC and WMVc% below cutoff values were more prone to develop disability worsening (unadjusted hazard ratio [HR] 3.875, p = 0.005; HR 4.246, p = 0.004, respectively). PBVC (HR 4.751, p = 0.008) and the interaction of new T2 lesions with WMVc% (HR 1.086, p = 0.005) were found to be independent predictors of disability worsening in the multivariate analysis.
  
  
  CONCLUSIONS
  At the patient level, whole-brain and white matter volume changes in the first year of interferon β therapy are predictive of subsequent clinical evolution under treatment.
authors.affiliation: Servei de Neurologia/Neuroimmunologia (F.C.P.-M., J.S.-G., A.V.-J., J.R., M.T., X.M.) Multiple Sclerosis Centre of Catalonia (Cemcat) and Unitat de Ressonància Magnètica (Servei de Radiologia) (C.A., D.P., A.R.), Hospital Universitari Vall d'Hebron, Barcelona, Spain; and Departament de Medicina (F.C.P.-M.), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Francisco Carlos
authors.initials: FC
authors.lastname: Pérez-Miralles
authors.affiliation: Servei de Neurologia/Neuroimmunologia (F.C.P.-M., J.S.-G., A.V.-J., J.R., M.T., X.M.) Multiple Sclerosis Centre of Catalonia (Cemcat) and Unitat de Ressonància Magnètica (Servei de Radiologia) (C.A., D.P., A.R.), Hospital Universitari Vall d'Hebron, Barcelona, Spain; and Departament de Medicina (F.C.P.-M.), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Sastre-Garriga
authors.affiliation: Servei de Neurologia/Neuroimmunologia (F.C.P.-M., J.S.-G., A.V.-J., J.R., M.T., X.M.) Multiple Sclerosis Centre of Catalonia (Cemcat) and Unitat de Ressonància Magnètica (Servei de Radiologia) (C.A., D.P., A.R.), Hospital Universitari Vall d'Hebron, Barcelona, Spain; and Departament de Medicina (F.C.P.-M.), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Vidal-Jordana
authors.affiliation: Servei de Neurologia/Neuroimmunologia (F.C.P.-M., J.S.-G., A.V.-J., J.R., M.T., X.M.) Multiple Sclerosis Centre of Catalonia (Cemcat) and Unitat de Ressonància Magnètica (Servei de Radiologia) (C.A., D.P., A.R.), Hospital Universitari Vall d'Hebron, Barcelona, Spain; and Departament de Medicina (F.C.P.-M.), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Río
authors.affiliation: Servei de Neurologia/Neuroimmunologia (F.C.P.-M., J.S.-G., A.V.-J., J.R., M.T., X.M.) Multiple Sclerosis Centre of Catalonia (Cemcat) and Unitat de Ressonància Magnètica (Servei de Radiologia) (C.A., D.P., A.R.), Hospital Universitari Vall d'Hebron, Barcelona, Spain; and Departament de Medicina (F.C.P.-M.), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Auger
authors.affiliation: Servei de Neurologia/Neuroimmunologia (F.C.P.-M., J.S.-G., A.V.-J., J.R., M.T., X.M.) Multiple Sclerosis Centre of Catalonia (Cemcat) and Unitat de Ressonància Magnètica (Servei de Radiologia) (C.A., D.P., A.R.), Hospital Universitari Vall d'Hebron, Barcelona, Spain; and Departament de Medicina (F.C.P.-M.), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Deborah
authors.initials: D
authors.lastname: Pareto
authors.affiliation: Servei de Neurologia/Neuroimmunologia (F.C.P.-M., J.S.-G., A.V.-J., J.R., M.T., X.M.) Multiple Sclerosis Centre of Catalonia (Cemcat) and Unitat de Ressonància Magnètica (Servei de Radiologia) (C.A., D.P., A.R.), Hospital Universitari Vall d'Hebron, Barcelona, Spain; and Departament de Medicina (F.C.P.-M.), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Tintoré
authors.affiliation: Servei de Neurologia/Neuroimmunologia (F.C.P.-M., J.S.-G., A.V.-J., J.R., M.T., X.M.) Multiple Sclerosis Centre of Catalonia (Cemcat) and Unitat de Ressonància Magnètica (Servei de Radiologia) (C.A., D.P., A.R.), Hospital Universitari Vall d'Hebron, Barcelona, Spain; and Departament de Medicina (F.C.P.-M.), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Alex
authors.initials: A
authors.lastname: Rovira
authors.affiliation: Servei de Neurologia/Neuroimmunologia (F.C.P.-M., J.S.-G., A.V.-J., J.R., M.T., X.M.) Multiple Sclerosis Centre of Catalonia (Cemcat) and Unitat de Ressonància Magnètica (Servei de Radiologia) (C.A., D.P., A.R.), Hospital Universitari Vall d'Hebron, Barcelona, Spain; and Departament de Medicina (F.C.P.-M.), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban