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How Can We Bring a Damaged Brain Back Into Action?

Richard G. Carson

Stroke: The Scale of the Problem §  Each year approximately 1 million people in

the EU suffer a stroke §  Of the three-quarters who survive:

§  20% become severely disabled §  30% become mildly to moderately disabled §  70% will have arm impairment

§  Stroke accounts for nearly 25% of all chronic disability in Europe

§  World wide, the number of stroke survivors has increased by 30% over the last decade

What is Stroke? §  Stroke is caused by insufficient oxygen to neural

tissue as a result of disruption to the vascular supply

The Principal Types of Stroke

Damage Resulting From Stroke §  Ischaemic core which is

irretrievably damaged §  Surrounding that core is

an area of termed the penumbra, which is potentially salvageable

§  Contemporary drug development focuses in part on restricting long term disruption to this region

Impairments of Movement §  Approximately 70% of strokes occur in the

middle cerebral artery §  this is the vascular supply to the cortical area

controlling movements of the upper limb §  therefore the incidence of upper limb disability is

high §  Functional consequences

§  muscle weakness §  loss of dexterity §  spasticity

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Are Adult Brains Fixed? §  “Once development is

complete, the sources of growth and regeneration of axons and dendrites are irretrievably lost. In the adult brain the nerve paths are fixed and immutable: everything can die, nothing can be regenerated”.

§  Thankfully, Cajal was incorrect! Ramón y Cajal(1852-1934)

Nerve Cells React to Stimuli §  The application of a

stimulus leads to changes of a twofold kind in the nervous system… the first property, by virtue of which the nerve cells react to the incoming impulse… we call excitability, and... changes arising…because of this property we shall call changes due to excitability. Jerzy Konorski (1903-1973)

What is Brain Plasticity? §  The second property, by

virtue of which certain permanent functional transformations arise in particular systems of neurons as a result of appropriate stimuli or their combination, we shall call plasticity and the corresponding changes plastic changes.

Sensory Brain Plasticity

Michael Merzenich

Cortical Map

Before After

Motor Brain Plasticity The Story So Far §  The adult brain retains an extensive facility to

undergo adaptive change - “neuroplasticity” §  Possible mechanisms of adaptation

§  unmasking of existing but functionally inactive pathways §  establishment of new neural connections

§  Plasticity of neural tissue is not in itself sufficient to induce recovery of motor function

§  It is necessary to utilise movement-based therapeutic interventions

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Constraint Induced Therapy Results of CI Therapy

Wolf et al. JAMA, 2006

Limitations of CI Therapy §  For many stroke survivors, the degree of

hemiparesis is so severe, that they are unable to generate levels of movement sufficient to use CIT

§  Alternative forms of movement therapy are required for those stroke survivors who have severely impaired upper limb function

Electrical Nerve Stimulation

Luigi Galvani (1737-1798)

Electrical Muscle Stimulation"

Duchenne de Boulogne(1806-1875)

EMG Triggered FES

EMG = Electromyography; FES = Functional Electrical Stimulation

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Results of EMG Triggered FES

Distance Reached

The Current Smart Arm

Electrical Brain Stimulation

Wilder Penfield (1891-1976)

Epidural Electrical Stimulation Changes in Hand Function Subscore of the Stroke Impact Scale

Brown et al. Neurosurgery, 2006

Faraday’s Principle

Michael Faraday (1791-1867)

Early Magnetic Brain Stimulation!

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Modern Magnetic Stimulation Neural Activation

Response Pathway Motor Evoked Potential (MEP) PRE POST

Voltage

Time

Change in Excitability

Repetitive TMS Therapy §  Khedr et al., Neurology,

2005 §  52 patients up to 2 weeks

after stroke §  Continue normal

treatment throughout §  rTMS (ten 10s trains at 3

Hz separated by 50s) at noon every day for 10 days

Results of rTMS Therapy

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Direct Current Stimulation

-70mV Resting Potential

Firing Threshold

ANODAL

CATHODAL

DC Stimulation Therapy

Hummel et al. Brain, 2005

Results of DC Therapy

Hummel et al. Brain, 2005

Summary §  The adult brain retains an extensive capacity

for adaptive change - “plasticity” §  Modern methods of non-invasive brain

stimulation may enhance normal processes of brain plasticity

§  When used in combination with movement therapy these techniques may help to promote recovery of function after brain injury.

Thank You For Your Attention!