New Directions For Neurorehabilitation Karunesh Ganguly, MD PhD - - PowerPoint PPT Presentation

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STROKE AND ANEURYSM UPDATE

September 6, 2014

New Directions For Neurorehabilitation

Karunesh Ganguly, MD PhD

Assistant Professor, Department of Neurology University of California, San Francisco Staff Physician, Neurology & Rehabilitation, SFVAMC

I have nothing to disclose.

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DISCLOSURE

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OUTLINE OF TOPICS

• Predicting recovery in individual patients
• Cortical basis of recovery & neuromodulation
• Rehabilitation robotics

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PREDICTING RECOVERY

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POTENTIAL FOR RECOVERY

General characteristics at population level

• Age, infarct size & location, acute treatment regimen, medical co-

morbidities Exam findings

• Independent digit movements, shoulder movements, ankle

dorsiflexion Neurophysiological & Imaging

• Transcranial magnetic stimulation assess motor pathways
• Neuroimaging structural and diffusion weighted

What about predicting recovery for individual patients?

• Multimodal assessment shows promise (exam, TMS, MRI)
• Predicting Recovery Potential (PREP) algorithm (Stinear et al.,

Brain, 2012)

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TMS

TMS = Transcranial Magnetic Stimulation MEP = Motor Evoked Potential

MEP

TMS stimulus artifact

Amplitude (mV) Time (ms)

• 10 0

50 1

• 1

MEP

EMG Recording

TMS

MULTIMODAL ASSESSMENTS TO PREDICT RECOVERY

Adapted from Stinear et al., Brain 2012

PREP Algorithm

• 40 patients with stoke

(cortical & subcortical) assessed at day 3 and reevaluated at 3 months

• SAFE (Shoulder Abduction

& Finger Extension) Score

• TMS & MEP
• DWI MRI

SAFE Score < 8 TMS MEP Negative MRI Diffusion Asymmetry Index ≥ 8, Complete recovery MEP +; Notable recovery (-); Limited (+); None

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MULTIMODAL ASSESSMENTS TO PREDICT RECOVERY

Stinear et al., Brain 2012

ARAT

• Grasp (6)
• Grip (4)
• Pinch (6)
• Gross (3)

Items used…

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Cortical basis for spontaneous recovery & Neuromodulation

NEURAL BASIS FOR RECOVERY

ARM FUNCTION glial reaction synaptogenesis fMRI activity O Week 8

Ipsilesional Hemisphere

O Week 8 glial reaction synaptogenesis fMRI activity

Contralesional Hemisphere

Adapted from Cramer, Ann Neurol, 2008

REPAIR MECHANISMS

• Growth factors
• GABA receptor
• Angiogenesis
• Inflammation
• Dendritic branching
• Axonal Sprouting
• Cell-cycle proteins
• Excitability

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IMBALANCE OF INHIBITION

Rheme et al., 2011 Ward and Grefkes, 2013

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NON-INVASIVE NEUROMODULATION

Imbalance of inter-hemispheric inhibition

Low-frequency (1 Hz) rTMS

• - - -
• - - -
• - - -
• - - -

High-frequency (> 3Hz) rTMS

+ + + + + + + + + + + + + + + +

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NEUROMODULATION WITH R-TMS

• 48 patients, randomized into 3 groups
• Sham, 3Hz and 10 Hz rTMS of affected hemisphere
• 5 days of stimulation at 130% of UH rest MEP
• Rehab regimen?

4=Moderate Severe; Dependent on ADLs; Unable to walk 1=No significant disability; Able to perform usual tasks Khedr et al., 2010

META-ANALYSIS OF TMS TRIALS

Hsu et al., Stroke 2012

Studies (n=18)

• Small studies with ~10 patients from 2005-2012
• Randomized but not blinded
• 1 Hz rTMS over the unaffected hemisphere (n=8)
• r HFS rTMS to affected hemisphere
• Outcome measures were variable
• Minimal adverse effects (HA, fatigue)
• Subgroup analysis favored 1Hz rTMS over the

unaffected hemisphere

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NEUROANATOMICAL BASIS FOR TMS RESPONSE

Ameli et al., Ann Neurol, 2012

• 29 patients (16 subcortical, 13 cortical involvement)
• Single dose of 10Hz (5s/25s for 20x over ~6 min)
• 30% increase in speed of finger and hand taps for subcortical only

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REHABILITATION ROBOTICS

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UPPER-LIMB ROBOTICS

Maciejasz, et al., 2014

Arm, hand, fingers

• 7 DOF in proximal
• 19 DOF in the hand/fingers
• >20 years of research into

rehabilitation robotics

• Based on research in motor

learning and adaptation

• Important clinical trials in the last

few years

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UPPER LIMB ROBOTS AFTER STROKE

Lo et al., NEJM 2010

• 128 patients robotic, ICT, usual care
• Moderate-severe (FGM ~20)
• Mean time from stroke ~4 years
• Four modules:
• Shoulder–elbow unit; an antigravity unit for vertical

movements; wrist unit and a grasp unit

• 12 weeks of training consisted of four training

blocks and were supervised by a therapist.

• Training progressed from proximal (shoulder,

wrist, hand grasp)

• Final 3 week block, all three devices were used to

integrate proximal to distal

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ROBOTIC VS INTENSIVE VS ‘USUAL’

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COMPLEX UPPER LIMB ROBOTICS

• 7 DOF
• Shoulder, elbow, wrist,

hand open/close

• Gaming environment for

target movements, ADLs, ROM

• Therapist can modify

Lancet Neurology, 2014

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PATIENT POPULATION

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OUTCOMES

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OUTCOMES

Cochrane Review (2012) Patients who receive electromechanical and robot Rx are more likely to improve their generic activities of daily living but not arm muscle strength.

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CONCLUSION

• Decades of basic research has built a foundation for

evaluating and developing new treatments

• Individualized predictive models and treatment plans

seem quite feasible

• Neuromodulation via stimulation is very promising
• Rehabilitation robotics can offer a viable alternative.

Possible home-based rx?