Hyunwoo Lee1, Kunio Nakamura2, Sridar Narayanan1, Robert Brown1, Jacqueline Chen3, Harold L Atkins4, Mark S Freedman5, Douglas L Arnold1. 1. McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada. 2. McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada/Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. 3. Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. 4. Ottawa Hospital Blood and Marrow Transplant Program, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada. 5. Department of Medicine (Neurology), The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada.
Abstract
BACKGROUND: Immunoablation and autologous hematopoietic stem cell transplantation (IA/aHSCT) halts relapses, white matter (WM) lesion formation, and pathological whole-brain (WB) atrophy in multiple sclerosis (MS) patients. Whether the latter was due to effects on gray matter (GM) or WM warranted further exploration. OBJECTIVE: To model GM and WM volume changes after IA/aHSCT to further understand the effects seen on WB atrophy. METHODS: GM and WM volume changes were calculated from serial baseline and follow-up magnetic resonance imaging (MRI) ranging from 1.5 to 10.5 years in 19 MS patients treated with IA/aHSCT. A mixed-effects model with two predictors (total busulfan dose and baseline T1-weighted WM lesion volume "T1LV") characterized the time-courses after IA/aHSCT. RESULTS: Accelerated short-term atrophy of 2.1% and 3.2% occurred in GM and WM, respectively, on average. Both busulfan dose and T1LV were significant predictors of WM atrophy, whereas only busulfan was a significant predictor of GM atrophy. Compared to baseline, a significant reduction in GM atrophy, not WM atrophy, was found. The average rates of long-term GM and WM atrophy were -0.18%/year (standard error (SE): 0.083) and -0.07%/year (SE: 0.14), respectively. CONCLUSION: Chemotherapy-related toxicity affected both GM and WM. WM was further affected by focal T1-weighted lesion-related pathologies. Long-term rates of GM and WM atrophy were comparable to those of normal-aging.
BACKGROUND: Immunoablation and autologous hematopoietic stem cell transplantation (IA/aHSCT) halts relapses, white matter (WM) lesion formation, and pathological whole-brain (WB) atrophy in multiple sclerosis (MS) patients. Whether the latter was due to effects on gray matter (GM) or WM warranted further exploration. OBJECTIVE: To model GM and WM volume changes after IA/aHSCT to further understand the effects seen on WB atrophy. METHODS: GM and WM volume changes were calculated from serial baseline and follow-up magnetic resonance imaging (MRI) ranging from 1.5 to 10.5 years in 19 MSpatients treated with IA/aHSCT. A mixed-effects model with two predictors (total busulfan dose and baseline T1-weighted WM lesion volume "T1LV") characterized the time-courses after IA/aHSCT. RESULTS: Accelerated short-term atrophy of 2.1% and 3.2% occurred in GM and WM, respectively, on average. Both busulfan dose and T1LV were significant predictors of WM atrophy, whereas only busulfan was a significant predictor of GM atrophy. Compared to baseline, a significant reduction in GM atrophy, not WM atrophy, was found. The average rates of long-term GM and WM atrophy were -0.18%/year (standard error (SE): 0.083) and -0.07%/year (SE: 0.14), respectively. CONCLUSION: Chemotherapy-related toxicity affected both GM and WM. WM was further affected by focal T1-weighted lesion-related pathologies. Long-term rates of GM and WM atrophy were comparable to those of normal-aging.
Entities:
Keywords:
Multiple sclerosis; atrophy; axonal loss; magnetic resonance imaging
Authors: Anastasie M Dunn-Pirio; Benjamin M Heyman; Dan S Kaufman; Revere P Kinkel Journal: Curr Treat Options Neurol Date: 2019-10-17 Impact factor: 3.598
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