Neuro Rehabilitation in Stroke

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					      Neuro-Rehabilitation in Stroke:

             Past, present, and future

             Carolee J. Winstein, PhD, PT, FAPTA
              University of Southern California

Western States Stroke Consortium: Seattle, WA, Sept 13-14, 2003
The New Millennium: After the decade of the BRAIN
Recovery – interaction of neural and
behavioral events:
Spontaneous neural recovery
 Behavioral compensation
 Functional recovery

Behavioral Compensation         Functional Recovery

Response to damage and       Response to a behavioral
behavioral attempts to       experience that enhances functional
compensate for effects of    outcomes and promotes functional
damage.                      reorganization.
 Brain-Behavior Interactions
How to harness them to enhance recovery
  Need to integrate the current science into the
What are the limitations? Critical factors?
  Dose-response; active participation
What are the factors that will help us
predict positive interactions and outcomes?
  Clinical tests of stroke severity, lesion
  information, patient perspectives
What the basic science tells us about the
functional reorganization of motor cortex:

Post-injury behavioral training can influence
structural plasticity (Nudo et al. 1996, Jones et al.,1996).
Skill acquisition is more important than
movement repetition (repetitive use) for
functional reorganization (Plautz et al., 2000).
Nudo, Barbay, & Kleim, 2000
A paradigm shift in neuro-rehabilitation:

It has long been recognized that practice is
essential for the acquisition of skilled motor
behavior in health, but only recently has this
notion been applied to neuro-rehabilitation.
 RCT research motivated by the science
     for evidence-based practice:
Stroke Arm Recovery in acute stroke (STAR)

Extremity Constraint-Induced Therapy
Evaluation in sub-acute stroke (EXCITE)

Strength-training effectiveness post-stroke
in chronic stroke (STEPS)
 RCT research motivated by the science
     for evidence-based practice:
Stroke Arm Recovery in acute stroke (STAR)

Extremity Constraint-Induced Therapy
Evaluation in sub-acute stroke (EXCITE)

Strength-training effectiveness post-stroke
in chronic stroke (STEPS)
    A Randomized Controlled Comparison of Upper
        Extremity Intervention Strategies in
    Participants with Acute Stroke: A Pilot Study

 Motor Behavior Laboratory
 University of Southern California

 Winstein CJ, Rose DK, Tan SM, Lewthwaite R, Chui HC, Azen SP
                          Supported by NIH, HD36212

Winstein et al., (in press) Arch Phys Med Rehabil
Background and Rationale:
Of all impairments that result from stroke, perhaps the most
serious, and most needing of rehabilitation effectiveness studies
is hemiparesis of the upper limb.
Population-based statistics indicate between 73% and 88% of
first time strokes (infarctions only) result in an acute
hemiparesis of the upper and/or lower limbs.
The upper limbs are of special concern because the impact of
upper extremity impairments on disability and health is so
Only limited attention has been given to upper extremity
rehabilitation following stroke, and functional recovery of the
arm and hand are generally quite limited compared with that for
the lower extremities.
Current approaches for UE
rehabilitation promote compensation

  Nakayama and colleagues (1994) concluded
   that recovery of upper extremity function
   in the majority of patients is achieved only
   by compensation using the unaffected
   upper extremity.

Copenhagen stroke study: based on the FIM and knowledge
of spontaneous recovery
          Orpington Prognostic Scale
                Range 1.6 - 6.8

     Orpington               Orpington
   Range: 1.6 - 4.1        Range: 4.2 - 6.8

 Less Severe (LS)          More Severe (MS)

Kalra & Crome, 1993
Trial Design:

      20 1-hr sessions
      over 4-6 weeks
    3 treatment groups

Pre-test       Post-test   6 months   9 months

                               Functional Task
                               Training (FT) +
 Care (SC)
                               Standard Care
   N = 20                          N = 20
14 LS 6 MS                      12 LS 8 MS
             Training (ST) +
                  N = 20
              14 LS 6 MS
Outcome Measures
Upper Extremity Fugl-Meyer Motor Score (Fugl-Meyer et
al, 1975)

UE Isometric Muscle Torque (Bohannon & Smith, 1987)
   shoulder (flex/ext), elbow (flex/ext), wrist (flex/ext)

Grip, Lateral Pinch, Palmar Pinch

Functional Test Hemiparetic Upper Extremity
   (FTHUE), (Wilson et al., 1984)
Self-Care FIM (Keith et al., 1987)
   eating, grooming, toileting, showering, dressing
                                        Fugl-Meyer Motor Score across Time

       UE Fugl-Meyer Motor Score   70
                                   60                                   *
                                   40                                        ST
                                   20                                        SC
                                         pre-test post-test   6 mo   9 mo
                                                  Evaluation Point
  *p < .05
Less Severe Cohort only
                Functional Test for the Hemiparetic
                         Upper Extremity

                6                                      SC
                    pre-test post-test   6 mo   9 mo
                            Evaluation Point
Less Severe Cohort only
Change in Self-Care FIM Score
                        Less Severe                                                More Severe

                       30                                                     30
Postscore - Prescore

                                                       Postscore - Prescore
                       25                                                     25

                       20                                                     20

                       15                                                     15

                       10                                                     10

                        5                                                      5

                        0                                                      0
                             SC        FT      ST                                   SC      FT    ST
                            n = 14   n = 12   n = 14                                n=6    n=8    n=6

                                     Group                                                Group
                                   FIM vs FTHUE
                               Baseline Orpington: 3.2
                                    (Three cases)
                  FIM                                              FTHUE

                                                                      SC      FT          ST
                      SC      FT         ST


                                                FTHUE Score
FIM Score




             7                                                0
                  B    Post   B    Post                            Baseline        Post
                 Self-care    Mobility
                                       UE Muscle Torque across Time

     UE Muscle Torque (kg-cm)

                                1500                                       FT


                                       pre-test post-test   6 mo    9 mo
                                                 Evaluation Point
  *p < .05
Less Severe Cohort only
Conclusion from STAR:
Results of STAR RCT suggest: specificity of training and
stroke severity are important factors for recovery and
rehabilitation of arm use in the acute stage.

An additional 20 hours of upper extremity-specific
therapy distributed over 4-6 weeks positively influenced
both immediate and longer-term outcomes only for the less
severe cohort.

While the immediate benefits of a functional-task specific
protocol were similar to those of a strength/motor control
protocol, and both were superior to standard care
immediately post-treatment, the functional-task practice
protocol was most beneficial at follow-up (9 months after
RCT research motivated by the science for
        evidence-based practice:

 Stroke Arm Recovery in acute stroke (STAR)

 Extremity Constraint-Induced Therapy
 Evaluation in sub-acute stroke (EXCITE)

 Strength-training effectiveness post-stroke
 in chronic stroke (STEPS)
  EXCITE Project
Extremity Constraint-Induced Therapy Evaluation
Multi-Center NCT (HD37606)
National Institutes of Health

    Steven Wolf, PhD, PT, FAPTA (Emory U., PI)
    Carolee J. Winstein, PhD, PT, FAPTA (USC, Co-PI)
Multi-site RCT:
  Five sites in the U.S. (USC, UF, OSU, Emory,
  UNC/Wake Forest, UAB)
  Data management center (Wash U.—J. Philip
  Administrative center (Emory U.--Steve
  Wolf, PI)
  Training center (UAB--David Morris, PT)
National Clinical Trial (2000-2005)
  Background and Rationale
  Overview of protocol (n = 240, 6 sites)
  Inclusion criteria
  Pilot test results
  Where we are now
Hypothesis: potential function that
function that is not expressed
Excess motor disability that is substantially
greater than appears warranted by the
organic condition (physiology)
  Lashley, 1924
  Tower, 1940
  Andrews & Stewart, 1979--”He can but does he..”
Not a new idea…

JAMA, Dec 18, 1915
One mechanism for this effect:
effect: Learned-non-use
 Mott & Sherrington (1895)
 Taub (1980)
 Taub et al., (1994)
   only when the “normal” limb was restricted, did
   the animal begin to use the deafferented limb.
Evolution of “forced use” in humans with
          humans with stroke
  Family of interventions collectively called “constraint-
  induced therapy” (CIT).
     Ostendorf & Wolf (1981)
     Wolf et al., (1989)
     Taub et al., (1993)
     Crocker et al., (1997) --in CP
     Van der Lee et al., (1999)
     Blanton & Wolf (1999)--subacute stroke case
     Dromerick et al., (2000)--acute stroke
How much practice do patients with
with stroke get in rehabilitation?

 Lincoln et al., 1996
   proportion of time spent in therapeutic activity was
   low; only 36 min/day in contact with either
   physiotherapist or occupational therapist; “in all
   settings observed patients spent many hours doing
Current medical “practice” models in stroke
 stroke rehabilitation are not optimal for
 optimal for studies that address the
 the impact of task-specific practice on
 on motor recovery.

   Shorter and shorter stays (reduced time)

   Time spent teaching compensation techniques--
   this shows up as big difference between adm
   and dc status (e.g., FIM change score)
Intervention Protocol:
 two weeks; 6 hr/day in training lab
 combination mitt with functional task practice and
adapted task practice (shaping)
 daily diary; behavioral contract
 mitt is worn 90% of waking hours (target)
Effects of intensity of training...

   Kwakkel et al. (1997, 1999)….
   Winstein et al., (in press)…even 1 hr/day
   hr/day of additional UE specific therapy is
   therapy is more beneficial than standard
   standard care in a group of participants in
   participants in the acute stage after stroke,
   stroke, but only in the less severe
   (Orpington scale) group.
Pre-test: Picking up a soda can
                             Subject: LCVA,
                             2.5 y post

                             Item on Wolf
                             Motor Function

                             39 s pre-test
Post-test: Picking up a soda can

                           Item on the Wolf
                           Motor Function Test

                           2 s post-test
Training beyond the present capability?

 Nudo et al., (1992) J Neurosci. 12:2918-2947
Nudo et al., (1997) Seminars in Neuroscience 9:13-23
 Not all repetitive behavioral experience
 results in cortical map modifications...

Nudo et al., (1997) Seminars in Neuroscience 9:13-23
Learning-dependent hypothesis

  “…prerequisite factor determining
  determining whether or not cortical
  cortical representational plasticity occurs
  occurs may be the acquisition of a novel
  novel skill (i.e. learning).”

    Plautz et al., 2000
Nudo et al., (1997) Seminars in Neuroscience 9:13-23
Examples of the “small well” type task…
Discovery/learning of new strategy (implicit)…
Study Design:
Randomized (immediate vs delayed)
Single-blind (evaluator is blinded to group)
Cross-over (delayed group gets intervention)
Outcome measures: (pre, post, every 4 mo for 2 yrs)
  Both impairment and disability will be measured.
  Motor Activity Log (MAL)
  Actual Amount of Use Test (AAUT)
  Wolf Motor Function Test (WMFT)
  Accelerometry (quantification of arm use)
Secondary measures:
  HROQ--Stroke Impact Scale (Duncan et al., 1999)
  Behavioral kinematics and intersegmental changes (UNC)
  Functional brain changes (fMRI, TMS)
Other critical components:
  Behavioral contract with specific home
  tasks that are customized to the patient’s
  daily activities pattern.
  Caregiver contract
  Home diary (daily)
  Compliance device inside Mitt
Motor Activity Log: Amount
0 - did not use my weaker arm
1 - occasionally tried to use my weaker arm (very rarely)
2 - sometimes used my affected arm, but did most of
the activity with my stronger arm (rarely).
3 - used my weaker arm about half as much as before the
stroke (half prestroke).
4 - used my weaker arm almost as much as before the
stroke (3/4 prestroke)
5 - used my weaker arm as much as before the stroke
(same as prestroke).

 30 different questions: “In the last three days, how often
 did you…..use your weaker arm to turn on a light with a
 light switch”?
Inclusion criteria:
Subjects who are between 3-9 months post-stroke (sub-acute)
Minimum motor criteria:
  --high level: 20 deg active wrist /; 10 deg of active MP and IP /
  of all fingers and thumb
  --low level: no less than 10 deg active wrist /; 10 deg of active
  abd/ exten of thumb and / of at least 2 other digits (3 x in 1
Score at least 24 on MMSE
Must score less than 2.5 on MAL amount of use (avg of 30 items)
Passive ROM criteria for shoulder, elbow, wrist and fingers
Over age of 18
 Inclusion criteria continued:
Subjects with sensory loss are eligible
Must be Ind. and safe in toilet transfers; stand
from sitting and maintain standing balance for 2
min with or without UE support
Subjects with neglect will be accepted if other
criteria met
No formal physical rehab program or concurrent
clinical trials
Medication is OK but no experimental field
study; prior phenol, Bo-tox, Baclofen
Is the behavior automatic and spontaneous?
Pilot Data (n = 14)
Active participation ~ Impairment
 Minimum motor criteria implies some
 some preservation of the corticospinal
 corticospinal pathway for wrist, hand, and
 hand, and finger voluntary control
 Lesion analysis ~ minimum motor criteria
 What percentage of stroke population
 population might benefit from CIT?
 What role does motor skill
 learning play in this process?

Lifting of
learned                     Skill
suppression                 acquisition
n                           n

        Initial Impairment level
Initial impairment level influences participation
participation and outcome to CIT (two case
case studies)

Subject   F-M (Motor)   MAL (amount)    MAL (how well) MAL change (amount)

MC        60.5 pre      1.69 pre        1.72 pre      2.55
          65 post       4.24 post       3.88 post

BD        17 pre        1.64 pre        1.12 pre      0.64
          22 post       2.28 post       1.74 post

Winstein & Prettyman (in preparation)
Where are we now…?
Methods/Design paper published in
Neurorehabilitation and Neural Repair (Winstein
et al., Sept, 2003)

How many encounters to recruit 222
subjects? 3626 patient encounters across
the six sites.
How many high/low level subjects?
 RCT research motivated by the science
     for evidence-based practice:
Stroke Arm Recovery in acute stroke (STAR)

Extremity Constraint-Induced Therapy
Evaluation in sub-acute stroke (EXCITE)

Strength-training effectiveness post-stroke
in chronic stroke (STEPS)
 Project: STEPS
Strength Training Effectiveness Post-Stroke
David A. Brown, PT, PhD
Katherine J. Sullivan, PT, PhD
Sara Mulroy, PT, PhD
                                                                           USC-BKN & PT
                                                                              Center                           Multi-site
                                                                          SAP       DMSC                       Multi-institution
                                                           RCT Projects                    Network Sites
     Impairment (resources)-Function (skills)-Disability

                                                              phase III                           USC
           Central Data Management and Analysis

                                                              PEDALS                            RLANRC
                                                               phase I


                                                               phase I

                                                               phase I


                                                                                                           Visit us at:
Figure                                                                                          clinics
Evidence for locomotor-induced plasticity:

   Repetitive locomotor activity that
   optimizes the sensorimotor experience of
   walking resulted in changes in EMG
   amplitude and bursting patterns in
   spinalized cats and humans with SCI.

                             De Leon et al., 1998
                             Harkema et al., 1997
Courtesy of Kathy Sullivan, UCLA and USC
Sensorimotor experience and task-specific
training effect locomotor recovery:
  Body-weight support and repetitive treadmill
  stepping enhances locomotor recovery.
                                 Sullivan et al., 2002
                                 Visintin et al., 1998
  Human spinal locomotor circuits interpret
  locomotor sensory inputs demonstrating activity
  dependent learning.
                                 Harkema et al., 1997
Sullivan, 2001
            Pre-training   Post-training
                           (12 sessions)


 Sullivan et al. (2003)
Sullivan et al., 2002
STEPS Specific Aims - General

To determine the effectiveness of specific
 strength training protocols to promote
 locomotor recovery after stroke.
60 minutes/day; 4
days/week; over a 6
week period
Exercise Conditions:
  Body-weight supported
  treadmill training
Exercise Conditions:
  strength training
Exercise Conditions:
  strength training
Exercise Conditions:
  Low intensity upper
  limb ergometry
Outcome Measures - Primary
  10 meter timed walk with Functional
  Ambulation Classification (FAC)
  Initial stratification by self-selected
  overground walking speed of low (<0.5
  m/sec) versus high (>=0.5 m/sec) post-
  stroke function
Outcome Measures - Secondary
  L/E Fugl Meyer: LE motor function
  Muscle Strength testing – Biodex – isometric testing for
  both paretic and non-paretic.
    Muscles: ankle plantarflexion/dorsiflexion, knee flexion/extension,
    hip flexion/extension.
  Berg Balance Scale
Functional Limitation:
  6 minute walk test with Functional Ambulation Classification
Disability/Quality of Life:
  Stroke Impact Scale (SIS): QOL measure
  SF-36: HRQOL measure
Specific Aims #1
  Are functional outcomes (primarily, gait speed)
  improved with strength training as an adjunct to
  body weight supported treadmill training
  (BWSTT) in persons with chronic post-stroke
  Hypothesis: Individuals who undergo 6 weeks of
  strength training in addition to BWSTT will show
  greater changes in gait speed compared with
  BWSTT alone.
Design #1


Specific Aims #2
  Are functional outcomes improved with
  locomotor-based strength training (LBST)
  compared with muscle-specific strength
  training (MSST) as an adjunct to BWSTT?
  Hypothesis: Individuals who undergo 6
  weeks of LBST in addition to BWSTT will
  show greater changes in gait speed
  compared with MSST and BWSTT.
Design #2

Specific Aims #3
  Are functional outcomes improved with
  LBST as compared with BWSTT?
  Hypothesis: Individuals who undergo 6
  weeks of BWSTT alone will show greater
  changes in gait speed compared with LBST
Design #3


Progress Highlights – On Schedule
   All personnel hired and trained
   Standardization procedures developed and
   Recruited and initiated first 6 participants
   at USC, Rancho, and NWU
   Large database of potential participants
   for next 3 years
Innovations in neuro-rehabilitation emanate from
one key principle of motor learning:

  Task-specific practice is the most important
 factor for skill acquisition
   Functional task-specific practice can enhance
   recovery of upper extremity function (Winstein et al., in

   Constraint-Induced Therapy may be just “more of the
   same” practice of functional tasks (van der Lee et al. 2001)
   Body weight supported treadmill training at higher
   velocities is better for recovery of locomotor
   function than slower velocities (Sullivan et al., 2002)
Your perspective on how the system works influences how
  you prioritize and implement a treatment to “fix” the
               system when it malfunctions.