Jessica M Cassidy1, George Tran2, Erin B Quinlan2, Steven C Cramer2. 1. From the Department of Neurology (J.M.C., S.C.C.), Department of Anatomy and Neurobiology (G.T., E.B.Q., S.C.C.), and Department of Physical Medicine and Rehabilitation (S.C.C.), University of California, Irvine. jcassid1@uci.edu. 2. From the Department of Neurology (J.M.C., S.C.C.), Department of Anatomy and Neurobiology (G.T., E.B.Q., S.C.C.), and Department of Physical Medicine and Rehabilitation (S.C.C.), University of California, Irvine.
Abstract
BACKGROUND AND PURPOSE: Patient heterogeneity reduces statistical power in clinical trials of restorative therapies. Valid predictors of treatment responsiveness are needed, and several have been studied with a focus on corticospinal tract (CST) injury. We studied performance of 4 such measures for predicting behavioral gains in response to motor training therapy. METHODS: Patients with subacute-chronic hemiparetic stroke (n=47) received standardized arm motor therapy, and change in arm Fugl-Meyer score was calculated from baseline to 1 month post-therapy. Injury measures calculated from baseline magnetic resonance imaging included (1) percent CST overlap with stroke, (2) CST-related atrophy (cerebral peduncle area), (3) CST integrity (fractional anisotropy) in the cerebral peduncle, and (4) CST integrity in the posterior limb of internal capsule. RESULTS: Percent CST overlap with stroke, CST-related atrophy, and CST integrity did not correlate with one another, indicating that these 3 measures captured independent features of CST injury. Percent injury to CST significantly predicted treatment-related behavioral gains (r=-0.41; P=0.004). The other CST injury measures did not, neither did total infarct volume nor baseline behavioral deficits. When directly comparing patients with mild versus severe injury using the percent CST injury measure, the odds ratio was 15.0 (95% confidence interval, 1.54-147; P<0.005) for deriving clinically important treatment-related gains. CONCLUSIONS: Percent CST injury is useful for predicting motor gains in response to therapy in the setting of subacute-chronic stroke. This measure can be used as an entry criterion or a stratifying variable in restorative stroke trials to increase statistical power, reduce sample size, and reduce the cost of such trials.
BACKGROUND AND PURPOSE:Patient heterogeneity reduces statistical power in clinical trials of restorative therapies. Valid predictors of treatment responsiveness are needed, and several have been studied with a focus on corticospinal tract (CST) injury. We studied performance of 4 such measures for predicting behavioral gains in response to motor training therapy. METHODS:Patients with subacute-chronic hemiparetic stroke (n=47) received standardized arm motor therapy, and change in arm Fugl-Meyer score was calculated from baseline to 1 month post-therapy. Injury measures calculated from baseline magnetic resonance imaging included (1) percent CST overlap with stroke, (2) CST-related atrophy (cerebral peduncle area), (3) CST integrity (fractional anisotropy) in the cerebral peduncle, and (4) CST integrity in the posterior limb of internal capsule. RESULTS: Percent CST overlap with stroke, CST-related atrophy, and CST integrity did not correlate with one another, indicating that these 3 measures captured independent features of CST injury. Percent injury to CST significantly predicted treatment-related behavioral gains (r=-0.41; P=0.004). The other CST injury measures did not, neither did total infarct volume nor baseline behavioral deficits. When directly comparing patients with mild versus severe injury using the percent CST injury measure, the odds ratio was 15.0 (95% confidence interval, 1.54-147; P<0.005) for deriving clinically important treatment-related gains. CONCLUSIONS: Percent CST injury is useful for predicting motor gains in response to therapy in the setting of subacute-chronic stroke. This measure can be used as an entry criterion or a stratifying variable in restorative stroke trials to increase statistical power, reduce sample size, and reduce the cost of such trials.
Authors: Cheryl Bushnell; Janet Prvu Bettger; Kevin M Cockroft; Steven C Cramer; Maria Orlando Edelen; Daniel Hanley; Irene L Katzan; Soeren Mattke; Dawn M Nilsen; Tepring Piquado; Elizabeth R Skidmore; Kay Wing; Gayane Yenokyan Journal: Circ Cardiovasc Qual Outcomes Date: 2015-10
Authors: Winston D Byblow; Cathy M Stinear; P Alan Barber; Matthew A Petoe; Suzanne J Ackerley Journal: Ann Neurol Date: 2015-11-17 Impact factor: 10.422
Authors: Benjamin N Groisser; William A Copen; Aneesh B Singhal; Kelsi K Hirai; Judith D Schaechter Journal: Neurorehabil Neural Repair Date: 2014-02-11 Impact factor: 3.919
Authors: David J Lin; Alison M Cloutier; Kimberly S Erler; Jessica M Cassidy; Samuel B Snider; Jessica Ranford; Kristin Parlman; Fabio Giatsidis; James F Burke; Lee H Schwamm; Seth P Finklestein; Leigh R Hochberg; Steven C Cramer Journal: Stroke Date: 2019-10-25 Impact factor: 7.914
Authors: Christiaan Hendrik Bas van Niftrik; Martina Sebök; Giovanni Muscas; Marco Piccirelli; Carlo Serra; Niklaus Krayenbühl; Athina Pangalu; Oliver Bozinov; Andreas Luft; Christoph Stippich; Luca Regli; Jorn Fierstra Journal: J Cereb Blood Flow Metab Date: 2019-02-12 Impact factor: 6.200
Authors: Morgan L Ingemanson; Justin R Rowe; Vicky Chan; Jeff Riley; Eric T Wolbrecht; David J Reinkensmeyer; Steven C Cramer Journal: Neurorehabil Neural Repair Date: 2019-07-18 Impact factor: 3.919
Authors: Jessica M Cassidy; Anirudh Wodeyar; Jennifer Wu; Kiranjot Kaur; Ashley K Masuda; Ramesh Srinivasan; Steven C Cramer Journal: Stroke Date: 2020-04-17 Impact factor: 7.914
Authors: Elizabeth Regan; Julius Fridriksson; Sydney Y Schaefer; Chris Rorden; Leonardo Bonilha; Jennapher Lingo VanGilder; Jill Campbell Stewart Journal: Exp Brain Res Date: 2020-11-01 Impact factor: 1.972
Authors: Steven C Cramer; Steven L Wolf; Jeffrey L Saver; Karen C Johnston; J Mocco; Maarten G Lansberg; Sean I Savitz; David S Liebeskind; Wade Smith; Max Wintermark; Jordan J Elm; Pooja Khatri; Joseph P Broderick; Scott Janis Journal: Stroke Date: 2021-02-10 Impact factor: 7.914