Modern approaches in
neurorehabilitation
NICK WARD, UCL INSTITUTE OF NEUROLOGY, QUEEN SQUARE
[email protected]
Follow us on twitter @Wardlab
Royal Society of Medicine, London, 29th January 2013
Recovery After Stroke: Neurorehabilitation
I.
The problem – framework for approaches to upper limb
treatment after stroke
II. Neuroplasticity as the key to recovery?
III. Taking advantage of plasticity - driving motor recovery
through practice
IV. Enhancing plasticity – pharmacotherapy
V. Enhancing plasticity – cortical stimulation
VI. Understanding variability through neuroimaging
Recovery after stroke: Neurorehabilitation
I. The problem
Recovery after stroke: Neurorehabilitation
I. Thomas Twitchell, Brain, 1954
“Unless the first two or three
weeks witness material change
for the better, prognosis should
be expressed in guarded terms”
Wilson, 1941
Recovery after stroke: Neurorehabilitation
I. Compensation vs Recovery
“…it is useful to divide
neurorehabilitation into
(1) measures primarily aimed at
assisting adaptation to (or
compensating for) impairment, and
(2) those primarily aimed at reducing
impairments.
The latter address underlying
neurological deficits more directly
but are relatively poorly understood”
Recovery after stroke: Neurorehabilitation
I. How do we treat people after stroke?
1.
2.
3.
4.
5.
Preservation of tissue
Avoid complications
Enhancement of plasticity
Task specific training
Compensation
Rehabilitation
Recovery
Recovery after stroke: Neurorehabilitation
I. When should we treat people after stroke?
1. EARLY – helps avoid complications
2. Natural history of recovery may be misleading
3. Can late treatment change impairment?
This patient made 90%
improvement 20 years after stroke
Recovery
What doafter
we mean
stroke:
byNeurorehabilitation
reorganisation?
II. What is brain plasticity?
Brain plasticity! Hold on ….. the cortex is not capable
of plasticity but is hardwired and immutable. Once
damage occurs, cortical neurons either die or at best
do not change their projection patterns…..”
Recovery after stroke: Neurorehabilitation
II. What is brain plasticity - structure?
Axon arborisation in vivo
Hua et al., Nature 2005; 434: 1022-1026
Niell et al., Nat Neurosci 2004; 7: 254-260
Dendritic growth in vivo
dendrites
axon
Recovery after stroke: Neurorehabilitation
II. What is brain plasticity - excitability?
• Reduced activity at GABAergic
interneurons allows plasticity e.g.
reopening critical period in adults
• Enhanced glutamatergic signalling
leads to LTP of connections
• Altering the balance of
inhibition/excitation away from
inhibition is important in allowing new
periods of plasticity in adult cortex
Recovery after stroke: Neurorehabilitation
II. What is brain plasticity?
Activity takes advantage
of plastic changes, but
also enhances them
These are therefore
therapeutic targets for
the promotion of
recovery after stroke
activity
lesion induced
changes
inactivity
Recovery after stroke: Neurorehabilitation
III. How do we treat people after stroke?
Rehabilitation is a process of active change by which a person
who has become disabled acquires the knowledge and skills
needed for optimum physical, psychological and social function
Treatments aimed at reducing impairments
Task-specific training
cortical
stimulation
other
drugs
Recovery
after stroke:
Neurorehabilitation
Does
it work
- Dose
III. Task specific practice (makes perfect)
Problem: average amount of out-patient speech therapy ~ 12 hours
Recovery after stroke: Neurorehabilitation
III. Task specific practice (makes perfect)
Dose is important
Motor – 1000’s of repetitions
Language – 100 hours
Recovery after stroke: Neurorehabilitation
III. How to increase the dose?
Robotic treadmill training
Home video arm/hand training
Robotic arm training
Recovery after stroke: Neurorehabilitation
III. How to increase the dose?
Recovery after stroke: Neurorehabilitation
IV. Pharmacotherapy after stroke
Recovery after stroke: Neurorehabilitation
IV. Pharmacotherapy after stroke
• chronic administration of SSRI fluoxetine
reinstates ocular dominance plasticity in
adulthood i.e. reopens critical period for
plasticity
• …reverses amblyopia
• ...reduces intracortical inhibition
• ...blocked by diazepam (GABAA agonist)
• ...increases expression of BDNF
In humans (healthy and stroke), a single dose
• increases simple motor performance
• increases motor cortex activity (fMRI)
• increases motor cortex excitability (TMS)
Recovery after stroke: Neurorehabilitation
IV. Pharmacotherapy after stroke
Lancet Neurol 2011;10:123-30
•
118 patients with ischemic stroke and hemiparesis (Fugl-Meyer scores ≤55)
•
fluoxetine (n=59; 20 mg once per day, orally) or placebo (n=59)
•
3 months starting 5 to 10 days after the onset of stroke
•
All patients had physiotherapy as delivered in local unit
•
The primary outcome measure was change in the FM score between day 0 and 90
Recovery after stroke: Neurorehabilitation
IV. Pharmacotherapy after stroke
Lancet Neurol 2011;10:123-30
less disability
Improved FM score at 90 days
more disability
Improved mRS score at 90 days
Recovery after stroke: Neurorehabilitation
IV. Pharmacotherapy after stroke
Several agents considered:
•
Acetylcholinesterase inhibitors
•
Amphetamine
•
DA agonists (e.g. DARS in UK)
Enhanced
plasticity
Reduced GABAergic inhibition?
Increased glutamatergic/BDNF mediated LTP?
Recovery after stroke: Neurorehabilitation
V. Cortical Stimulation after stroke
Transcranial Magnetic Stimulation
Transcranial DC Stimulation
Enhancing ipsilesional excitability or
decreasing contralesional excitability of
motor cortex might enhance motor learning
by altering balance of excitation/inhibition
Ward & Cohen, 2004
Recovery after stroke: Neurorehabilitation
V. Cortical Stimulation after stroke
Recovery after stroke: Neurorehabilitation
V. Cortical Stimulation after stroke
Recovery after stroke: Neurorehabilitation
VI. Barriers to translation
None have entered into routine
clinical practice – why?
Recovery after stroke: Neurorehabilitation
VI. Understanding variability
input
input
input
input
Ward and Cohen, Arch Neurol 2004
Recovery after stroke: Neurorehabilitation
VI. Changing motor networks after stroke
affected
side
A
10 days
post stroke
infarct
B
17 days
post stroke
24 days
post stroke
31 days
post stroke
3 months
post stroke
affected
side
OUTCOMES
Barthel
ARAT
GRIP
NHPT
Patient A
20/20
57/57
98.7%
78.9%
Patient B
20/20
57/57
64.2%
14.9%
Recovery after stroke: Neurorehabilitation
VI. Predicting treatment response
unaffected
+
affected
-
unaffected
+
affected
-
Will the same treatment strategy work in these patients?
Recovery after stroke: Neurorehabilitation
VI. Predicting outcome by measuring structural damage
• Database of (i) hi-res structural MRI, (ii)
language scores and (iii) time since stroke
• MRI converted to 3D image with index of degree
of damage at each 2mm3 voxel
• This lesion image compared to others in
database and similar patients identified
• Different ‘recovery’ curves can then be
estimated for different behavioural measures
Recovery after stroke: Neurorehabilitation
VI. Multimodal stratification after stroke
Stinear, C. M. et al. Brain 2007 130:170-180
Copyright restrictions may apply.
Recovery after stroke: Neurorehabilitation
Summary
• Advances in neurorehabilitation are coming about through
advances in neuroscience
• The dose of treatment is critical - more is generally better
• Enhancement of plasticity is possible
• Neuroimaging should help in stratification
• Understanding the mechanisms of recovery and treatment
might allow targeted or individualised therapy after stroke in
future
Recovery after stroke - Neurorehabilitation
Acknowledgements
FIL:
ABIU/NRU:
SOBELL DEPARTMENT :
Richard Frackowiak
Diane Playford
Marie-Helen Boudrias
Rosalyn Moran
Richard Greenwood
Holly Rossiter
Karl Friston
Alan Thompson
Chang-hyun Park
Will Penny
Martin Brown
Karine Gazarian
Jennie Newton
All nurses, physios, OTs, SLTs
Emma Davis
Peter Aston
Stephanie Bowen
Eric Featherstone
Sven Bestmann
John Rothwell
Penny Talelli
Some more slides at www.ucl.ac.uk/ion/departments/sobell/Research/NWard
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FUNDING:
Ward Lab at UCL or @WardLab