Tomoko Kitago, MD American Society of Neurorehabilitation November 10, 2016 San Diego, CA

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1 EARLYPATIENT RECOVERY DEMOGRAPHIC OF MOTOR CONTROL CHARACTERISTICS AFTER AND STROKE: A HUMAN LONGITUDINAL PERSPECTIVE CLINICAL DATA Tomoko Kitago, MD American Society of Neurorehabilitation November 10, 2016 San Diego, CA

2 None Disclosures

3 Time course of stroke recovery Lessons from animal models Responses to injury occur early, and the sensitive period is short-lived From Murphy and Corbett, 2009

4 Studying stroke recovery in humans Stroke Body function / impairment Activity Participation True"Recovery Compensation

5 Study of Motor Learning and Acute Recovery Time-course after Stroke SMARTS John Krakauer (PI) Johns Hopkins University (Pablo Celnik) Columbia University (Tomoko Kitago and Joel Stein) University of Zurich (Andreas Luft)

6 SMARTS timeline subacute chronic 2 wks 1 mo 3 mo 6 mo 12 mo Four approaches at each time point 1. Physiological: TMS 2. Behavioral: arm kinematics, finger individuation, fmri 3. Anatomical: DTI, ASL 4. Clinical

7 SMARTS timeline subacute chronic 2 wks 1 mo 3 mo 6 mo 12 mo Four approaches at each time point 1. Physiological: TMS 2. Behavioral: arm kinematics, finger individuation, fmri 3. Anatomical: DTI, ASL 4. Clinical

8 peak speed minimize compensation and antigravity effort planar, 8 cm KineReach figure adapted from Mani and Sainburg et al. Brain 2013

9 y (cm) healthy stroke x (cm)

10 Spontaneous recovery of proximal motor control is over in about a month Paretic Non-paretic Ctrl non-dominant Ctrl dominant AMD Week Ctrl Cortes et al., in preparation

11 Finger individuation task

12 Xu et al., in submission

13 Time A limited time window for spontaneous motor recovery after stroke

14 Early spontaneous recovery follows a proportional recovery rule Fugl-Meyer Motor Assessment from initial (24-72 hrs) to 90 days post stroke FM = b (FM max FM initial ) b = 0.7 Prabhakaran et al. Neurorehabilitation and Neural Repair (2008)

15 Proportional recovery Findings reproduced in multiple stroke populations: Zarahn et al., Cerebral Cortex 2011 Winters et al., NNR 2015 Byblow et al., Ann Neurol 2015

16 Current clinical practice is not enough Acute rehabilitation 3 hours of therapy; average length of stay in 2009 = 14 days Mean # repetitions ~30 for skilled tasks using upper extremity (Lang et al 2009) During inpatient rehab, patients physically active only 13% of the time, in bed 53% of the time (Bernhardt et al 2004)

17 More conventional therapy does not improve upon spontaneous recovery Recovery not influenced by time spent in therapy Minutes in upper limb therapy Byblow et al., Ann Neurol 2015

18 Rehabilitation in the chronic post-stroke state

19 Constraint-induced movement therapy Restraint of the good limb + intensive training of the bad limb Intensive task-oriented training Mitt restraint when not in therapy

20 Study of CIMT 10 patients with chronic stroke and residual UE paresis 4 hours of CIMT per day, for 10 consecutive weekdays, and wearing of a mitt CIMT led to small improvements in arm activity (Action Research Arm Test), but not changes in arm impairment (Fugl-Meyer)

21 No improvement in motor control after CIMT Figure 2. A Healthy Pre-training Post-training B C E F Arm 5 cm D Wrist 2 cm Kitago et al. NNR 2013

22 Robotic therapy Ability to deliver high intensity therapy Paired with game goals, feedback, motivation Measurement capability

23 Robotics: REO GO Motorika 27 hours of robotic therapy, over 3 weeks

24 Motor control in chronic stroke minimally responds to robotic training No significant changes in FM-UE or ARAT, but motor control did improve Red= Pre-training Blue = Post-training Kitago et al J Neurophys (2015)

25 There is a limited time window of spontaneous motor recovery. Current standard therapy has little effect on early spontaneous biological recovery. In the chronic stage, effects on arm impairment are small, if any. Robotics has some promise for reducing impairment.

26 Approaches to improving upon spontaneous biological recovery Pre-Stroke Time after stroke

27 Columbia Jessica Berard Juan Camilo Cortes Jeff Goldsmith Michelle Harran Isis Martinez Heidi Schambra Joel Stein ETH Zurich Meret Brandscheidt Joachim Cerny Ben Hertler Andreas Luft Johns Hopkins John Krakauer (PI) Pablo Celnik Nathan Kim Susan Rice Jing Xu Other Joern Diedrichsen Suellen Jones Saunders Memorial Fund

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