title: Brain atrophy after bone marrow transplantation for treatment of multiple sclerosis.
abstract: BACKGROUND
  A cohort of patients with poor-prognosis multiple sclerosis (MS) underwent chemotherapy-based immune ablation followed by immune reconstitution with an autologous hematopoietic stem cell transplant (IA/aHSCT). This eliminated new focal inflammatory activity, but resulted in early acceleration of brain atrophy.
  
  
  OBJECTIVE
  We modeled the time course of whole-brain volume in 19 patients to identify the baseline predictors of atrophy and to estimate the average rate of atrophy after IA/aHSCT.
  
  
  METHODS
  Percentage whole-brain volume changes were calculated between the baseline and follow-up magnetic resonance imaging (MRI; mean duration: 5 years). A mixed-effects model was applied using two predictors: total busulfan dose and baseline volume of T1-weighted white-matter lesions.
  
  
  RESULTS
  Treatment was followed by accelerated whole-brain volume loss averaging 3.3%. Both the busulfan dose and the baseline lesion volume were significant predictors. The atrophy slowed progressively over approximately 2.5 years. There was no evidence that resolution of edema contributed to volume loss. The mean rate of long-term atrophy was -0.23% per year, consistent with the rate expected from normal aging.
  
  
  CONCLUSIONS
  Following IA/aHSCT, MS patients showed accelerated whole-brain atrophy that was likely associated with treatment-related toxicity and degeneration of "committed" tissues. Atrophy eventually slowed to that expected from normal aging, suggesting that stopping inflammatory activity in MS can reduce secondary degeneration and atrophy.
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors.forename: Hyunwoo
authors.initials: H
authors.lastname: Lee
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors.forename: Sridar
authors.initials: S
authors.lastname: Narayanan
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Brown
authors.affiliation: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Jacqueline T
authors.initials: JT
authors.lastname: Chen
authors.affiliation: Ottawa Hospital Blood and Marrow Transplant Program, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Harold L
authors.initials: HL
authors.lastname: Atkins
authors.affiliation: University of Ottawa and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Freedman
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Arnold
mesh_terms: D000328:Adult; D001284:Atrophy / Q000209:etiology; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D001921:Brain / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology / Q000628:therapy*; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous / Q000009:adverse effects; D055815:Young Adult
keywords: Multiple sclerosis; atrophy; bone marrow transplantation; magnetic resonance imaging; models; statistical; transplantation conditioning