Contributions
Abstract: P1000
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Progressive MS
Background: Primary-progressive MS (PPMS) is characterized by progression of disability from disease onset without occurrence of relapses, and is associated with diffuse damage in normal appearing brain tissue. Diffusional kurtosis imaging (DKI) is a sensitive indicator of tissue damage and provides pathologically specific information on microstructural changes.
Objectives: To characterize the extent of microstructural pathologic changes in a PPMS cohort over a short-term follow-up period (1 year), and to explore their relationship with clinical disability.
Methods: We recruited 26 patients (14 F) with PPMS, mean age 50.92±10.30 years, median Expanded Disability Status Scale (EDSS) 4.0 (range 1.5-6.0), mean 9-Hole Peg Test (9HPT) 33.89±15.33 seconds and 25-foot walking test (25FWT) 7.34±2.16 seconds, Paced Auditory Serial Addition Test (PASAT-3") -0.30±0.92 and 20 controls (11 F), mean age 51.05±9.80 years. The 3T magnetic resonance imaging (MRI) protocol included T2-weighted Turbo-Spin-Echo; b) T1-weighted 3D Fast-Field-Echo; c) twice-refocused spin echo for DKI at both time points.
DKI was processed using Diffusional Kurtosis Estimator and FSL software to obtain fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), axonal diffusion (DA), axial and radial diffusion of the extra-axonal space (Dax, Drad), axonal water fraction (AWF) and tortuosity; for all the DKI metrics, maps were derived and compared between groups using a Tract-based Spatial Statistics (TBSS). Voxelwise non-parametric paired t-tests were used to measure changes from baseline to follow-up, linear correlations between DKI and clinical metrics were tested with non-parametric permutation inference.
Results: TBSS at baseline showed a widespread pattern of changes in FA, MD, MK, AWF and tortuosity in MS subjects in comparison with controls and a more restricted decrease in DA and Dax. At one year, the widespread MK decrease was confirmed and a significant decrease in AWF, mainly localized in the corpus callosum (CC), was detected. AWF changes in the splenium of the CC and antherior thalamic radiation were correlated with follow-up EDSS and Multiple Sclerosis Functional Composite (MSFC) respectively (TFCE, p< 0.05 corrected for voxelwise multiple comparisons for all tests).
Conclusions: DKI derived metrics are sensitive to short-term microstructural changes in PPMS and their change over time correlates with clinical disability.
Disclosure: M. Petracca, C. Saiote L. Fleysher, M. Fabian, J. Howard, C. Farrell have nothing to disclose. Dr. Aaron Miller has served as a consultant and/or participant in advisory board meetings for Genzyme/sanofi-aventis, Biogen Idec, Glaxo Smith Kline, EMD Serono (Merck Serono), Novartis, ONO, Acorda, Nuron Biotech,Teva, Questcor and Accordant Health Services. He has received research support from Acorda, Novartis, Genentech, Genzyme/sanofi-aventis, Biogen Idec, Roche, and Questcor. He has served as Editor of Continuum, a continuing medical education publication of the AAN and currently serves as Editor of Continuum Audio. He is a member of the editorial board of Multiple Sclerosis and Related Disorders. He occasionally performs expert reviews of medical records or serves as an expert witness in medical malpractice cases. Dr. Fred Lublin Sources of Funding for Research: Acorda Therapeutics, Inc.; Biogen Idec; Novartis Pharmaceuticals Corp; Teva Neuroscience, Inc.; Genzyme; Sanofi; Celgene; NIH; NMSS; Consulting Agreements/Advisory Boards/DSMB: Bayer HealthCare Pharmaceuticals; Biogen Idec; EMD Serono, Inc.; Novartis; Teva Neuroscience; Actelion; Sanofi-Aventis; Acorda; Questcor; Roche, Genentech; Celgene; Johnson & Johnson; Revalesio; Coronado Bioscience, Genzyme, MedImmune; Bristol-Myers Squibb, Xenoport, Receptos; Forward Pharma; Co-Chief Editor: Multiple Sclerosis and Related Diseases; Stock Ownership: Cognition Pharmaceuticals, Inc. Dr. Matilde Inglese has received research grants from NIH, NMSS, Novartis Pharmaceuticals Corp., Teva Neuroscience.
Abstract: P1000
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Progressive MS
Background: Primary-progressive MS (PPMS) is characterized by progression of disability from disease onset without occurrence of relapses, and is associated with diffuse damage in normal appearing brain tissue. Diffusional kurtosis imaging (DKI) is a sensitive indicator of tissue damage and provides pathologically specific information on microstructural changes.
Objectives: To characterize the extent of microstructural pathologic changes in a PPMS cohort over a short-term follow-up period (1 year), and to explore their relationship with clinical disability.
Methods: We recruited 26 patients (14 F) with PPMS, mean age 50.92±10.30 years, median Expanded Disability Status Scale (EDSS) 4.0 (range 1.5-6.0), mean 9-Hole Peg Test (9HPT) 33.89±15.33 seconds and 25-foot walking test (25FWT) 7.34±2.16 seconds, Paced Auditory Serial Addition Test (PASAT-3") -0.30±0.92 and 20 controls (11 F), mean age 51.05±9.80 years. The 3T magnetic resonance imaging (MRI) protocol included T2-weighted Turbo-Spin-Echo; b) T1-weighted 3D Fast-Field-Echo; c) twice-refocused spin echo for DKI at both time points.
DKI was processed using Diffusional Kurtosis Estimator and FSL software to obtain fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), axonal diffusion (DA), axial and radial diffusion of the extra-axonal space (Dax, Drad), axonal water fraction (AWF) and tortuosity; for all the DKI metrics, maps were derived and compared between groups using a Tract-based Spatial Statistics (TBSS). Voxelwise non-parametric paired t-tests were used to measure changes from baseline to follow-up, linear correlations between DKI and clinical metrics were tested with non-parametric permutation inference.
Results: TBSS at baseline showed a widespread pattern of changes in FA, MD, MK, AWF and tortuosity in MS subjects in comparison with controls and a more restricted decrease in DA and Dax. At one year, the widespread MK decrease was confirmed and a significant decrease in AWF, mainly localized in the corpus callosum (CC), was detected. AWF changes in the splenium of the CC and antherior thalamic radiation were correlated with follow-up EDSS and Multiple Sclerosis Functional Composite (MSFC) respectively (TFCE, p< 0.05 corrected for voxelwise multiple comparisons for all tests).
Conclusions: DKI derived metrics are sensitive to short-term microstructural changes in PPMS and their change over time correlates with clinical disability.
Disclosure: M. Petracca, C. Saiote L. Fleysher, M. Fabian, J. Howard, C. Farrell have nothing to disclose. Dr. Aaron Miller has served as a consultant and/or participant in advisory board meetings for Genzyme/sanofi-aventis, Biogen Idec, Glaxo Smith Kline, EMD Serono (Merck Serono), Novartis, ONO, Acorda, Nuron Biotech,Teva, Questcor and Accordant Health Services. He has received research support from Acorda, Novartis, Genentech, Genzyme/sanofi-aventis, Biogen Idec, Roche, and Questcor. He has served as Editor of Continuum, a continuing medical education publication of the AAN and currently serves as Editor of Continuum Audio. He is a member of the editorial board of Multiple Sclerosis and Related Disorders. He occasionally performs expert reviews of medical records or serves as an expert witness in medical malpractice cases. Dr. Fred Lublin Sources of Funding for Research: Acorda Therapeutics, Inc.; Biogen Idec; Novartis Pharmaceuticals Corp; Teva Neuroscience, Inc.; Genzyme; Sanofi; Celgene; NIH; NMSS; Consulting Agreements/Advisory Boards/DSMB: Bayer HealthCare Pharmaceuticals; Biogen Idec; EMD Serono, Inc.; Novartis; Teva Neuroscience; Actelion; Sanofi-Aventis; Acorda; Questcor; Roche, Genentech; Celgene; Johnson & Johnson; Revalesio; Coronado Bioscience, Genzyme, MedImmune; Bristol-Myers Squibb, Xenoport, Receptos; Forward Pharma; Co-Chief Editor: Multiple Sclerosis and Related Diseases; Stock Ownership: Cognition Pharmaceuticals, Inc. Dr. Matilde Inglese has received research grants from NIH, NMSS, Novartis Pharmaceuticals Corp., Teva Neuroscience.