AButler5-15-06Final

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Presenter Disclosure Information FINANCIAL DISCLOSURE: This work was funded in part by NIH R01 NS 40984 and RO1 HD 37606. Andrew J. Butler, Ph.D. PT

Upper limb stroke rehabilitation research ongoing at Emory University : 

Upper limb stroke rehabilitation research ongoing at Emory University Andrew J. Butler, PhD, MPT Assistant Professor, Emory University, Department of Rehabilitation Medicine Faculty, Program in Physical Therapy, Neuroscience and Psychology Research Health Scientist, Atlanta VA Medical Center Tri-State stroke network meeting, May 15, 2006, Chapel Hill, NC

Elias A. Zerhouni, NIH director: “Roadmap” for medical research in the 21st century : 

Elias A. Zerhouni, NIH director: “Roadmap” for medical research in the 21st century NIH Roadmap http://nihroadmap.nih.gov/index.asp New pathways to discovery Imaging Bioinformatics and computational biology New research teams of the future Interdisciplinary research Re-engineering the clinical research enterprise Bench-to-bedside approach

Intro and background : 

Intro and background Old theories, “You are born with finite set of brain cells” or “The brain is a hardwired black-box” Contemporary ideas Ability to generate new neurons Functional reorganization of existing dendritic and synaptic connections (Merzenich, Nudo, Jones, Shallert, others) Following injury to the cortex, behavioral experience plays a key role in modifying the functional organization of remaining intact cortical tissue.

What is Neural Plasticity? : 

What is Neural Plasticity? “Plasticity is the most abused word in neuroscience”, says Roger Nicoll-UCSF Virtually any change in the brain, from the chemical level to the formation of new neurons (i.e. neurogenesis) to the remapping of larger regions. The brains ability to change and reorganize in response to some change in input from internal or external sources (Clifford, 2003). Experience-independent (Shatz, 1992), Experience-expectant, Experience-dependent (Black and Greenough, 1997)

Learned Non-Use : 

Learned Non-Use Reluctance or unwillingness to use the hemiplegic limb due to initial weakness or incoordination that eventually leads to a learned suppression of movement.

Constraint-induced therapy involves teaching a stroke survivor to regain use of his or her impaired arm by limiting the use of the stronger arm. : 

Constraint-induced therapy involves teaching a stroke survivor to regain use of his or her impaired arm by limiting the use of the stronger arm.

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OVERCOMING LEARNED NON-USE Forced use Repetitive task practice

INTERVENTIONEXCITE Trial Protocol : 

INTERVENTIONEXCITE Trial Protocol Wearing a restraint over a period of two weeks on the less involved limb Training for 10 days of the two weeks of restraint

Summary: EXCITE 1Year Data : 

Summary: EXCITE 1Year Data Both groups improve in primary outcome measures at one year Magnitude of improvement at each time point favors the CI Therapy group Clinically relevant improvements show a similar behavior Few serious adverse events that do not appear related to the intervention

Lab Research Perspectives : 

Lab Research Perspectives COMPONENTS: Interventional: Physical (Constraint-induced therapy, ASAP-USC) Virtual Environment ( Atlanta VA Rehab R and D, MIT) Visual mental imagery (Butler, G. Yue Cleveland Clinic) Air Muscle- assistive repetitive motion device (Emory-CCF) Subthreshold electrical stimulation delivered concurrent with rehabilitation activities in patients with hemiparesis (Northstar neuroscience- Everest Trial) rTMS- Stimulation of the cortex has both excitatory and inhibitory influences (Butler, Epstein, Wolf) Mechanistic fMRI/TMS (FICIT) (Emory, WFU, OSU) Biomechanics Kinematic, kinetic (CCF) Molecular – Biomarkers as precursors to neuronal reorganization. DTI, Magnetic Resonance Spectroscopy, etc.

Implantable Cortical Stimulation System Developed by Northstar Neuroscience, Inc : 

Implantable Cortical Stimulation System Developed by Northstar Neuroscience, Inc Locate site of hand function fMRI Place electrode On dura Implant pulse generator Stimulate during rehabilitation Caution: Investigational device. Limited by federal (or US) law to investigational use.

Adams Results: Upper Extremity Fugl-Meyer Scores29% Improvement : 

Adams Results: Upper Extremity Fugl-Meyer Scores29% Improvement ANOVA: P<0.0001 overall, P<0.0001 by Group, P=0.08 by Time, P=0.02 Group by Time Gray Area= Clinical Significance

Multi-modal imaging : 

Multi-modal imaging

Summary : 

Summary NIH Roadmap New pathways to discovery Imaging Bioinformatics and computational biology New research teams of the future Interdisciplinary research Re-engineering the clinical research enterprise Bench-to-bedside approach