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

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9/7/2013 STROKE AND ANEURYSM UPDATE DISCLOSURE September 7, 2013 I have nothing to disclose. New Directions For Neurorehabilitation Karunesh Ganguly, MD PhD Assistant Professor, Department of Neurology University of California, San

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9/7/2013 1

STROKE AND ANEURYSM UPDATE

September 7, 2013

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
  • Wearable robotics
  • Promising basic research findings

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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

What about predicting recovery for individual patients?

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

Brain, 2012)

6

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

8

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 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, 2009

  • 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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WEARABLE ROBOTS

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SLIDE 5

9/7/2013 5 ‘WEARABLE’ ROBOTS

Rosen Lab (UCSC) Ekso bionics

  • Univ. Washington

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INNOVATIVE BASIC SCIENCE

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PROMISING BASIC RESEARCH

Pharmacological modulation of perilesional inhibition

  • Clarkson et al., Nature 2010
  • Blockade of extrasynaptic GABA-R improved motor recovery

Modulation of molecules that inhibit axon sprouting

  • NOGO Receptor (Li et al., 2010)
  • Ephrin Receptor (Overman et al., 2012)

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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

  • Ongoing research should help develop and refine

specific approaches to rehabilitation

  • Neuromodulation via stimulation is very promising
  • Recent reports of innovative approaches suggest new

treatment options