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Gary M. Abrams MDProfessor of NeurologyUCSF

STROKE REHABILITATION - 2014

Outline• - Stroke Facts and Disability• - Basic Principles of Stroke Rehab• Why do it?• How is it done?• What’s the prognosis for recovery?• - The Road to Recovery• Key clinical trials in stroke rehabilitation

Treatments on the horizon

U.S. Stroke FactsStroke is 4th leading cause of death and leading cause of disability►795,000 new strokes/yr (AHA)►700,000 survivors/yr (CDC 2011)

Rehabilitation is needed by 45% - 60%►At 6 months -

• 70% - doing well• 30% - significantly disabled

Wade, 1994

Disabilities after Stroke - Frenchay Health District United Kingdom - 1981-1983

Type of Disability Acute (%) 6 mos. (%)

Mobility

Help with transfers from bed to chair 70 19

Unable to walk independently 73 15

Communication

Marked communication problems 52 15

ADLs

Needs help with grooming 56 13

Needs help with toileting 68 20

Needs help with feeding 68 33

Needs help with dressing 79 31

Needs help with bathing 86 49

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Rehabilitation for Stroke

�Why do it?

Langhorne et al, Lancet 1993; Langhorne and Duncan, Stroke 2001

Stroke Rehab – Why do it ?Meta-analysis of 10 trials1586 patients randomized to receive multidisciplinary team rehab vs. general medical careo 28% reduction in mortality at 4 monthso 21% reduction in mortality at 1 year

For every 100 patients receiving stroke rehab – an extra 5 return home independent

Cochrane Library, 2013

Comprehensive Stroke UnitsWhat’s the most effective setting? - Combination of acute care and rehabilitationWhy?- Dedicated and interested staff - prevent secondary

complications- Early and substantial family involvement - enriches the

environment- The most important “rehab” factor - early mobilization

The Cochrane Library “….stroke patients who receive organised inpatient

care in a stroke unit are more likely to be alive, independent, and living at home one year after the

stroke.

Rehabilitation for Stroke•Why do it?

�How is it done?

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Stroke Rehabilitation –Multidisciplinary Rehab Team►MD - leads team; addresses medical issues►RN - skin care; bowel and bladder function; patient and family education►Physical Therapist - mobility, strength and conditioning►Occupational Therapist - activities of daily living (ADLs) and functional transfers►Speech Pathologist - language, cognitive-perceptual training and dysphagia management►Social Worker - psychosocial issues, case management►Begin Stroke Rehab ASAP (A)

VA-DoD CPG 2005 Agency for Healthcare Policy and Research, 1995; VA-DoD CPG 2005

Stroke Rehab - How?�Perform baseline assessment

on admission�Develop explicit rehabilitation

goals and plan�Actively involve the patient

and family�Provide re-training for sensory

and motor deficits�Provide assistive devices to

facilitate independence in self care

�Ιdentify and treat cognitive-perceptual deficits�Identify depression and

provide treatment �Identify and treat speech and

language disorders �Educate the patient, family

and caregivers�Monitor progress�Develop a discharge plan

with continued services, as needed

Post-Stroke Depression (PSD)• Prevalence of 30% to 50% in the first year• Adversely affects physical recovery and overall

recovery• PSD worsens functional outcomes at 3 months

and 15 months• PSD is linked to increased risk of suicide and

overall mortality•

Antidepressants effectively treat PSD (Flaster et al., Topics Stroke Rehabil 2013;20:139-150)

Pharmacological Treatment of PSD

(Salter et al., J Stroke Cerebrovasc Dis, 2012)

0.001

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Rehabilitation for Stroke•Why do it?•How is it done?

�What is the prognosis?

Jorgesen et al, Arch Phys Med Rehab, 1995

Time to Recovery after Stroke – Copenhagen Stroke Study

Neurological Recovery:Scandinavian Stroke Scale

Functional Recovery:Barthel Index

The Stroke Recovery Timeline

Langhorne, Lancet Neurology 2010

BodyFunctions and Activities

Learning and CompensationNeural ReorganizationPhysical Fitness

Rehabilitation for Stroke•Why do it?•How is it done?•What is the prognosis for recovery?

� Where do we go from here?

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Clinical Trials in Stroke RehabFluoxetine for Motor Recovery after Stroke (FLAME) - Pharmacotherapy for global functional recoveryExtremity Constraint Induced Therapy Evaluation (EXCITE) - Rehabilitation training method for arm recoveryLocomotor Experience Applied Post-Stroke (LEAPS)- Body-weight supported treadmill training for

gait

FLAME Trial - Background• Monoamine drugs modulate brain plasticity and

outcomes after stroke• In experimental animals: • - amphetamines improve outcomes • - neuroleptics and benzodiazepines impair outcomes

How about selective serotonin reuptake inhibitors (SSRIs)?

• - Neuroprotective effects; promote hippocampal neurogenesis• - Small clinical studies - SSRIs enhance activation of motor

cortex and improve stroke outcome.

FLAME Trial - Background

Pariente at al, Annals of Neurology, 2001

SSRIs modulate motor performance and cerebral activation of patients recovering from stroke

FLAME Trial Chollet et al. Lancet Neurology 2011• Double-blind, placebo-controlled trial of fluoxetine

within 5 - 10 days of ischemic hemiparesiso 118 patients received fluoxetine 20 mg daily or

placebo x 3 months. o All patients received PT

• Primary outcome - Fugl-Meyer Motor Score (FMMS) • (Total score 0-100 – Arm - 66 points; Leg – 34 points)

• Secondary outcome - Modified Rankin Scale

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FLAME TRIAL – Primary EndpointFugl-Meyer Score

Severe:Lift paretic arm to wash axillaFugl-Meyer 11 to 14

Place arm into sleeveFugl-Meyer 19 to 22

What does a 3 Point Change on Fugl-Meyer Mean?Severe-Moderate Impairment

Moderate:Tuck shirt, hike pantsFugl-Meyer 25 to 28

FLAME TRIAL – Modified RankinChollet et al. Lancet Neurology 2011

•1 - No significant disability. Able to carry out all usual activities••2 - Slight disability. Looks after own affairs without assist, but unable to carry out all previous activities.••3 - Moderate disability. Requires some help, but walks unassisted.••4 - Moderately severe disability. Needs assist with own bodily needs and walking

•5 - Severe disability. Mead GE, Hsieh CF, Lee R, et al. Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database Syst Rev. 2012;(11):CD009286

EXCITE Trial – BackgroundTheory of “learned non-use” (Taub)• Monkeys with a paretic or sensory deprived limb will

“learn” not to use it• If the intact limb is constrained, movement in the

impaired limb improves• Creatively “forcing” the use of a hemiparetic limb

improves functional recovery

Treatment - “Constraint-induced therapy”

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Taub et al, Arch Phys Med Rehab 1993

Constraint-Induced Motor Therapy (CIMT)• Subjects:• - 9 stroke patients; >1 year after a stroke• - Hemiparetic with some use of arm• - 20° wrist extension and 10° finger extension

• Method:• Experimental group (4) – Subjects “forced” to use weak

arm, 6 hrs/day x 10 days in rehab; Good arm restrained 90% of waking hours for 2 weeks

• Control group (5) – “lots of attention” + passive movement

Outcome: Functional use of arm

EXCITE TrialWolf et al. JAMA 2006

222 patients - 3 to 9 months post-stroke- “Good” arm placed in a safety mitt for 90% of

waking hours x 2 weeks- Training (6 hours/day) on pre-selected tasks (e.g.,

wrapping a present; writing; etc.)- Controls – received “usual care”

Primary outcomes – Function at 1 year�Real world arm use – Motor Activity Log �Laboratory arm use – Wolf Motor Function Test

EXCITE Trial Outcome

CIMT

Usual Care

Motor Activity Log(MAL) (0 - 7.0)

Months

CIMT

Usual Care

Higher functioning subjects

Lower functioning subjects

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Constraint-Induced Motor Therapy

Jorgesen et al, Arch Phys Med Rehab, 1995

Time to Best Walking Based on Leg Severity (804 cases)Mild Paresis 4 weeks

95% at best walking function

Moderate Paresis

6 weeks

Severe Paresis

11 weeks

LEAPS Trial - Background• 1995 -2005 – Small studies

suggested that repetitive stepping using a treadmill might improve walking ability in stroke patients.

• Technique• Harness support and unweighting

(up to 40%) using a suspension device

• Assisted stepping with a physical therapist

PT + BWSTT PT

PT = Physical Therapy

BWSTT = Body weight-supported treadmill training

Hesse et al, Stroke 1995

Walking speed - Patients 3 months post-stroke

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LEAPS TrialDuncan et al, New Eng J Med 2011;364;2026• 408 stroke patients (mean age 62)

with severe/ moderate walking impairments randomly assigned into 3 study groups (a) Locomotor Training Program (LTP) - Early(b) Locomotor Training Program (LTP) - Late (c) Home Exercise Program - Early

36 training sessions (90 mins.) over 12 to 16 weeks.

LEAPS TrialDuncan et al, New Eng J Med 2011;364;2026

Subjects who had home PT improved walking ability equal to those treated with LTP• Walking speed gains of ~ 0.25 m/s• 6 minutes walking distance gain of ~ 80 meters

•

Subjects in the LTP group that started late (at 6 months) also made significant improvements in walking speed.

LEAPS TrialDuncan et al, New Eng J Med 2011;364;2026All training programs were highly effective in improving -

- Levels of walking ability - Functional status and quality of life at one year

post-stroke.

Conclusions:- Expensive equipment not necessary to achieve

gains- Walking ability can be improved late after stroke

© 2007 American Heart Association, Inc. Published by American Heart Association. 2

Treadmill Aerobic Training Improves Glucose Tolerance and Indices of Insulin Sensitivity in Disabled Stroke Survivors: A Preliminary Report.Ivey, Frederick; Ryan, Alice; Hafer-Macko, Charlene et al, Stroke. 38(10):2752-2758, 2007,

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Motor Function

Cognition/Language Sensory/Vision

Global Outcomes

• Multidisciplinary Stroke Unit care• Early supported discharge

services• Occupational therapy for ADLs• Outpatient rehabilitation services

to improve ADLs**

• Constraint-induced motor therapy**• Robot-assisted training for arm**• Task-oriented walking and physical

fitness training for walking speed and distance

Recommended, Evidence-Based Interventions Stroke Rehabilitation

• None• Treatment of depression

Robotic Training

Stem-cell therapy

Neuromodulation – transcranial magnetic stimulation

Fugl-Meyer Score - 38/66

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