Hyunwoo Lee1, Sridar Narayanan1, Robert A Brown1, Jacqueline T Chen2, Harold L Atkins3, Mark S Freedman4, Douglas L Arnold1. 1. McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada. 2. Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. 3. Ottawa Hospital Blood and Marrow Transplant Program, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada. 4. University of Ottawa and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada.
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. CONCLUSION: 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.
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. CONCLUSION: Following IA/aHSCT, MSpatients 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.
Entities:
Keywords:
Multiple sclerosis; atrophy; bone marrow transplantation; magnetic resonance imaging; models; statistical; transplantation conditioning
Authors: Chenyu Wang; Michael H Barnett; Con Yiannikas; Joshua Barton; John Parratt; Yuyi You; Stuart L Graham; Alexander Klistorner Journal: Neurol Neuroimmunol Neuroinflamm Date: 2019-07-16
Authors: Peter J Darlington; Brandon Stopnicki; Tarik Touil; Jean-Sebastien Doucet; Lama Fawaz; Morgan E Roberts; Marie-Noëlle Boivin; Nathalie Arbour; Mark S Freedman; Harold L Atkins; Amit Bar-Or Journal: Front Immunol Date: 2018-05-07 Impact factor: 7.561
Authors: Simon Thebault; Hyunwoo Lee; Gauruv Bose; Daniel Tessier; Mohammad Abdoli; Marjorie Bowman; Jason Berard; Lisa Walker; Carolina A Rush; Heather MacLean; Ronald A Booth; Sridar Narayanan; Douglas L Arnold; Vincent Tabard-Cossa; Harold L Atkins; Amit Bar-Or; Mark S Freedman Journal: Ann Clin Transl Neurol Date: 2020-04-18 Impact factor: 4.511