Contributions
Abstract: P758
Type: Poster
Abstract Category: Therapy - symptomatic - Treatment of specific symptoms
Objective and background: The majority of multiple sclerosis (MS) patients experience impaired walking ability which impacts quality of life. Timed 25-foot walk (T25FW) is commonly used to gauge gait impairment but varies widely and may be insensitive. Objective biological markers that correlate closely with disability are needed. Diffusion tensor imaging (DTI), quantifying fiber tract integrity, might provide such information. In this project we analyzed relationships between T25FW, conventional and DTI MRI markers.
Design and methods: A subset of our previously established cohort of gait-impaired patients we intended to treat with dalfampridine underwent brain and cervical spinal cord MRI. DTI mean diffusivity (MD), axial and radial diffusivity and fractional anisotropy (FA) were measured at brain cortico-spinal tracts (CST) and spinal rFOV at C2/3. We analyzed relationships between baseline T25FW, conventional and DTI MRI markers. We also identified the CST causing greater lateralized pyramidal dysfunction on neurological exam on a per-patient basis, and then used the brain DTI metrics from the causative tract in the regression analysis.
Results: Thirteen patients were imaged for this study. Mean T25FW was 8.26 sec, 61% of patients had progressive disease and 46% used a gait assistive device. Mean brain CST FA was 0.53 (SD=0.038), mean CST MD was 0.8x10-3 µm2/ms (SD=0.06). Mean brain CST axial diffusivity was 1.32 mm2/s ×10-3 (SD 0.06) and mean brain CST radial diffusivity was 0.54 mm2/s ×10-3 (SD 0.06).
Multivariate linear regression showed statistically significant associations between several MRI and DTI metrics and T25FW: brain MD CST (p= 0.004), brain CST axial and radial diffusivity (p= 0.004 and 0.02), GMV (p= 0.05), WMV (p= 0.03) and NBV (p= 0.01). The regression model containing MD CST and controlled for gait assistance was the best fit model (p= 0.004). Analysis of the brain CST causative of the pyramidal dysfunction showed significant association between T25FW and brain CST MD (p=0.023) as well as brain CST axial diffusivity (p=0.008).
Conclusions: Our results suggest an association between DTI metrics and gait impairment, evidenced by brain MD CST and T25FW. This could be explained by the higher sensitivity of DTI metrics for axonal damage and consequent disability. We plan to further utilize these results focusing on brain CST MD as a main candidate biomarker to predict dalfampridine response.
Disclosure:
B. N. Delman received compensation for consulting/ advisory board work for Bayer HealthCare.
M. Inglese received research grant from NIH, NMSS, Novartis Pharmaceuticals and Teva.
F.D. Lublin received compensation for consulting /advisory board work with Bayer HealthCare Pharmaceuticals; Biogen Idec; EMD Serono, Inc.; Novartis; Teva; Actelion; Sanofi/Genzyme; Acorda; Questcor/Malinckrodt; Roche/Genentech; Celgene, MedImmune; Osmotica; Xenoport, Receptos; Forward Pharma; BBB technologies; Akros; TG Therapeutics; Abbvie, research grants from Biogen Idec; Novartis Pharmaceuticals Corp; Teva, Inc.; Genzyme; Sanofi; Celgene; Transparency Life Sciences; NIH; NMSS.
S. Krieger received compensation for consulting /advisory board work with Acorda Therapeutics, Bayer HealthCare, Biogen Idec, EMD Serono, Genentech, Genzyme, Questcor, and Teva, and gave non-promotional lectures with Biogen Idec and Genzyme.
S.Klineova, R.Farber, C. Farrell, C. Saiote and J.Friedman have nothing to disclose.
Abstract: P758
Type: Poster
Abstract Category: Therapy - symptomatic - Treatment of specific symptoms
Objective and background: The majority of multiple sclerosis (MS) patients experience impaired walking ability which impacts quality of life. Timed 25-foot walk (T25FW) is commonly used to gauge gait impairment but varies widely and may be insensitive. Objective biological markers that correlate closely with disability are needed. Diffusion tensor imaging (DTI), quantifying fiber tract integrity, might provide such information. In this project we analyzed relationships between T25FW, conventional and DTI MRI markers.
Design and methods: A subset of our previously established cohort of gait-impaired patients we intended to treat with dalfampridine underwent brain and cervical spinal cord MRI. DTI mean diffusivity (MD), axial and radial diffusivity and fractional anisotropy (FA) were measured at brain cortico-spinal tracts (CST) and spinal rFOV at C2/3. We analyzed relationships between baseline T25FW, conventional and DTI MRI markers. We also identified the CST causing greater lateralized pyramidal dysfunction on neurological exam on a per-patient basis, and then used the brain DTI metrics from the causative tract in the regression analysis.
Results: Thirteen patients were imaged for this study. Mean T25FW was 8.26 sec, 61% of patients had progressive disease and 46% used a gait assistive device. Mean brain CST FA was 0.53 (SD=0.038), mean CST MD was 0.8x10-3 µm2/ms (SD=0.06). Mean brain CST axial diffusivity was 1.32 mm2/s ×10-3 (SD 0.06) and mean brain CST radial diffusivity was 0.54 mm2/s ×10-3 (SD 0.06).
Multivariate linear regression showed statistically significant associations between several MRI and DTI metrics and T25FW: brain MD CST (p= 0.004), brain CST axial and radial diffusivity (p= 0.004 and 0.02), GMV (p= 0.05), WMV (p= 0.03) and NBV (p= 0.01). The regression model containing MD CST and controlled for gait assistance was the best fit model (p= 0.004). Analysis of the brain CST causative of the pyramidal dysfunction showed significant association between T25FW and brain CST MD (p=0.023) as well as brain CST axial diffusivity (p=0.008).
Conclusions: Our results suggest an association between DTI metrics and gait impairment, evidenced by brain MD CST and T25FW. This could be explained by the higher sensitivity of DTI metrics for axonal damage and consequent disability. We plan to further utilize these results focusing on brain CST MD as a main candidate biomarker to predict dalfampridine response.
Disclosure:
B. N. Delman received compensation for consulting/ advisory board work for Bayer HealthCare.
M. Inglese received research grant from NIH, NMSS, Novartis Pharmaceuticals and Teva.
F.D. Lublin received compensation for consulting /advisory board work with Bayer HealthCare Pharmaceuticals; Biogen Idec; EMD Serono, Inc.; Novartis; Teva; Actelion; Sanofi/Genzyme; Acorda; Questcor/Malinckrodt; Roche/Genentech; Celgene, MedImmune; Osmotica; Xenoport, Receptos; Forward Pharma; BBB technologies; Akros; TG Therapeutics; Abbvie, research grants from Biogen Idec; Novartis Pharmaceuticals Corp; Teva, Inc.; Genzyme; Sanofi; Celgene; Transparency Life Sciences; NIH; NMSS.
S. Krieger received compensation for consulting /advisory board work with Acorda Therapeutics, Bayer HealthCare, Biogen Idec, EMD Serono, Genentech, Genzyme, Questcor, and Teva, and gave non-promotional lectures with Biogen Idec and Genzyme.
S.Klineova, R.Farber, C. Farrell, C. Saiote and J.Friedman have nothing to disclose.