ARTICLE CLASS OF EVIDENCE Intense Arm Rehabilitation Therapy Improves the Modified Rankin Scale Score Association Between Gains in Impairment and Function Steven C. Cramer, MD, Vu Le, MS, Jeffrey L. Saver, MD, Lucy Dodakian, MA, OTR/L, Jill See, PT, MPT, Renee Augsburger, OTR/L, Alison McKenzie, DPT, PhD, Robert J. Zhou, BA, Nina L. Chiu, BS, Jutta Heckhausen, PhD, Jessica M. Cassidy, DPT, PhD, Walt Scacchi, PhD, Megan Therese Smith, PhD, A.M. Barrett, MD, Jayme Knutson, PhD, Dylan Edwards, PhD, PT, David Putrino, PhD, PT, Kunal Agrawal, MD, Kenneth Ngo, MD, Elliot J. Roth, MD, David L. Tirschwell, MD, Michelle L. Woodbury, PhD, OTR/L, Ross Zafonte, DO, Wenle Zhao, PhD, Judith Spilker, BSN, RN, Steven L. Wolf, PT, PhD, Joseph P. Broderick, MD, and Scott Janis, PhD Neurology ® 2021;96:e1812-e1822. doi:10.1212/WNL.0000000000011667 Correspondence Dr. Cramer sccramer@mednet.ucla.edu Abstract Objective To evaluate the effect of intensive rehabilitation on the modified Rankin Scale (mRS), a measure of activities limitation commonly used in acute stroke studies, and to define the specific changes in body structure/function (motor impairment) most related to mRS gains. Methods Patients were enrolled >90 days poststroke. Each was evaluated before and 30 days after a 6-week course of daily rehabilitation targeting the arm. Activity gains, measured using the mRS, were examined and compared to body structure/function gains, measured using the Fugl- Meyer (FM) motor scale. Additional analyses examined whether activity gains were more strongly related to specific body structure/function gains. Results At baseline (160 ± 48 days poststroke), patients (n = 77) had median mRS score of 3 (interquartile range, 2–3), decreasing to 2 [2–3] 30 days posttherapy (p < 0.0001). Similarly, the proportion of patients with mRS score ≤2 increased from 46.8% at baseline to 66.2% at 30 days posttherapy (p = 0.015). These findings were accounted for by the mRS score decreasing in 24 (31.2%) patients. Patients with a treatment-related mRS score improvement, compared to those without, had similar overall motor gains (change in total FM score, p = 0.63). In exploratory analysis, improvement in several specific motor impairments, such as finger flexion and wrist circumduction, was significantly associated with higher likelihood of mRS decrease. Conclusions Intensive arm motor therapy is associated with improved mRS in a substantial fraction (31.2%) of patients. Exploratory analysis suggests specific motor impairments that might underlie this finding and may be optimal targets for rehabilitation therapies that aim to reduce activities limitations. RELATED ARTICLE Editorial Connecting Upper Limb Functional Stroke Recovery to Global Disability Measures: Finding the Forest in the Trees Page 643 MORE ONLINE Class of Evidence Criteria for rating therapeutic and diagnostic studies NPub.org/coe From the Department of Neurology (S.C.C., J.L.S.), University of California, Los Angeles; California Rehabilitation Institute (S.C.C.), Los Angeles; Department of Neurology (S.C.C., V.L., L.D., J. See, R.A., A.M., R.J.Z., N.L.C., J.M.C.), Department of Psychological Science (J.H.), Institute for Software Research (W.S.), and Department of Statistics (M.T.S.), University of California, Irvine; Department of Physical Therapy (A.M.), Chapman University, Irvine, CA; Department of Allied Health Sciences (J.M.C.), University of North Carolina at Chapel Hill; Department of Stroke Rehabilitation Research (A.M.B.), Kessler Foundation; Department of Stroke Rehabilitation (A.M.B.), Kessler Institute for Rehabilitation, West Orange, NJ; Department of Physical Medicine and Rehabilitation (J.K.), MetroHealth System, Case Western Reserve University, Cleveland, OH; Brain Stimulation and Robotics Laboratory (D.E.), Burke Neurological Institute; Department of Telemedicine and Virtual Rehabilitation (D.P.), Burke Medical Research Institute, White Plains, NY; Abilities Research Center (D.P.), Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Clinical Neurosciences (K.A.), University of California, San Diego, La Jolla; Brooks Rehabilitation Clinical Research Center (K.N.), Brooks Rehabilitation, Jacksonville, FL; Department of Physical Medicine and Rehabilitation (E.J.R.), Northwestern University, Chicago, IL; Department of Neurology (D.L.T.), University of Washington, Seattle; Departments of Health Science and Research (M.L.W.) and Public Health Sciences (W.Z.), Medical University of South Carolina, Charleston; Department of Physical Medicine and Rehabilitation (R.Z.), Spaulding Rehabilitation Hospital, Massachusetts General Hospital, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA; Department of Neurology (J. Spilker, J.P.B.), University of Cincinnati, OH; Department of Rehabilitation Medicine (S.L.W.), Division of Physical Therapy Education, Emory University, Atlanta, GA; Atlanta VA Health Care System (S.L.W.), Center for Visual and Neurocognitive Rehabilitation, Decatur, GA; and NINDS (S.J.), NIH, Bethesda, MD. Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. e1812 Copyright © 2021 American Academy of Neurology Copyright © 2021 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.