PM&R Research Day 2005!
A PILOT STUDYDEFINING CORTICAL REORGANIZATION
WITH THE USE OF CONSTRAINT INDUCED
MOVEMENT THERAPY
Presentation prepared by:
William Carey Scott, D.O.
Jennifer Elizabeth Marks, D.O.
Edward Babigumira, M.D.
Investigators

FH. Siddiqui, MB.ChB, HH. Stonnington, MD,
G.Glynn, MD, R. Rojas, MD, K. Kurtz Burke, MD, E.
Babigumira, MD, W.C. Scott, DO, J.E. Marks, DO,
L. Lemen, PhD, C.Cusick, PhD, KK.Ramsdell, MS,
LOTR, E.Taylor, PhD, LOTR, R. Jacobs, LOTR,
CHT, MI. Mehmood, BS, D.Mercante, PhD, K.
Andras, BA, MOTS; H.F. Devillier,BS, MOTS; S.
Montreuil, BS, MOTS
What is CIMT?

Constraint Induced
Movement Therapy

Involves intensive
training of the
hemiparetic limb,
while restricting use
of the unaffected
limb.
Literature Review of CIMT
CIMT Origins
 Ogden
R., Franz SI. On cerebral motor
control: the recovery from
experimentally induced hemiplegia.
Psychobiology 1917: 1:33-49.
 Constraint was attempted on primates
with pyramidal tract lesions
Arch Phys Med Rehabil. 1993 Apr;74(4):347-54.
Technique to improve chronic motor deficit after
stroke.
Taub E, Miller NE, Novack TA, Cook EW 3rd, Fleming
WC, Nepomuceno CS, Connell JS, Crago JE.
 The
unaffected upper extremity of chronic stroke
patients was restrained in a sling during waking
hours for 14 days; on ten of those days, these
patients were given six hours of practice in using
the impaired upper extremity
 The restraint subjects improved on each of the
laboratory measures of motor function used--in
most cases markedly
 These gains were maintained during a two-year
period of follow-up
Arch Phys Med Rehabil. 2001 Apr;82(4):524-8.
Constraint-induced motor relearning after stroke: a
naturalistic case report.
Sabari JS, Kane L, Flanagan SR, Steinberg A.
 The
patient sustained a right midpontine vascular
infarct and fell simultaneously, fracturing her right
humerus. Orthopedic intervention for the fracture
mirrored the protocol suggested by proponents of
CIMT by immobilizing her right arm. Her significant
recovery of left arm use over a 1-year period was
more extensive than what would be typically
expected after the type of cerebral infarct she
incurred. Her case provides the first evidence in
the literature that supports the principles of CIMT
when it is applied immediately poststroke.
Pediatr Rehabil. 2002 Jul-Sep;5(3):125-31.
The effectiveness of constraint induced movement
therapy in two young children with hemiplegia.
Glover JE, Mateer CA, Yoell C, Speed S.
 Case
reports for two hemiplegic children, ages 19
and 38 months, each of whom underwent a trial of
CIMT. Both children made significant gains in
upper arm function that were reflected in a variety
of domains, including aspects of everyday
functional limb use. Gains persisted to variable
degrees and some unexpected new gains were
noted following cessation of CIMT.
Pay attention now…
J Rehabil Med. 2003 May;(41 Suppl):41-5.
Constraint-induced movement therapy: some
thoughts about theories and evidence.
Van der Lee JH.
 In
this review four randomized clinical trials
are presented systematically.
 It is concluded that the learned non-use
theory requires further exploration and that
the evidence regarding the effectiveness of
CIMT is not yet conclusive.
Arch Phys Med Rehabil. 2002 Oct;83(10):1374-7.
Longer versus shorter daily constraint-induced
movement therapy of chronic hemiparesis: an
exploratory study.
Sterr A, Elbert T, Berthold I, Kolbel S, Rockstroh B,
Taub E.
 To
evaluate and compare the effects of 3-hour
versus 6-hour daily training sessions in constraintinduced movement therapy (CIMT).
 CIMT
(14 consecutive days; constraint of unaffected
hand for a target of 90% of waking hours) with either 6
hours (6h/d group, n=7) or 3 hours (3h/d group, n=8) of
shaping training with the affected hand per day.
 The 3-hour CIMT training schedule significantly improved
motor function in chronic hemiparesis, but it was less
effective than the 6-hour training schedule.
Ahh…very interesting.
Clin Rehabil. 2004 Feb;18(1):110-4.
Constraint-induced movement therapy: time for a
little restraint?
Siegert RJ, Lord S, Porter K.
 Examined
selected articles and related
publications concerning CIMT.
 Considerable evidence from case studies and
case series has accumulated but only a limited
number of randomized controlled trials (RCTs)
exist.
 CIMT may hold considerable promise, but
independent, large-scale, multicentre RCTs
comparing its effectiveness with conventional
therapy of equal intensity are required.
Our CIMT Study: Purpose

The functional benefits gained by stroke
patients through the use of constraint induced
movement therapy have been well
documented.
 Little information is known regarding the
reorganization of cortical processes resulting
from functional treatment and its implication
within the dynamic of neuronal plasticity.
 With the advent of functional magnetic
resonance imaging, there exists an
opportunity to utilize this technology to further
our understanding of this phenomenon.
Purpose
 Using
functional MRI, the present study
aims to contribute further information in
regard to cortical reorganization, in
addition, define a temporal window to
optimize the benefit of constraint
induced motor therapy.
fMRI

Functional MRI is based on the increase in
blood flow to the local vasculature that
accompanies neural activity in the brain
 Magnetic resonance imaging can be used to
map changes in brain hemodynamics that
correspond to mental operations. This is
postulated to extend traditional anatomical
imaging to include maps of human brain
function
 fMRI provides high resolution, noninvasive
reports of neural activity detected by a blood
oxygen level dependent signal
fMRI
fMRI

Rapidly emerging body of literature
documents corresponding findings between
fMRI and conventional electrophysiological
techniques to localize specific functions of the
human brain (Atlas, et al, 1996; Puce, et al,
1995; Burgess, 1995; Detre, et al, 1995;
George, et al, 1995; Ives, et al, 1993).
 Consequently, the number of medical and
research centers with fMRI capabilities and
investigational programs continues to
escalate.
I wish it was still Mardi Gras…
Neurorehabil Neural Repair. 2002 Dec;16(4):326-38.
Motor recovery and cortical reorganization after
constraint-induced movement therapy in stroke
patients: a preliminary study.
Schaechter JD, Kraft E, Hilliard TS, Dijkhuizen RM,
Benner T, Finklestein SP, Rosen BR, Cramer SC.
 The
goal of this study was to assess motor cortical
reorganization after CIMT using functional
magnetic resonance imaging (fMRI).
 4 incompletely recovered chronic stroke patients
treated with CIMT underwent motor function
testing and fMRI. Five age-matched normal
subjects were also imaged.
 Motor
function testing showed that patients made
significant gains in functional use of the strokeaffected upper extremity (detected by the Motor
Activity Log) and significant reductions in motor
impairment (detected by the Fugl-Meyer Stroke
Scale and the Wolf Motor Function Test)
immediately after CIMT, and these effects
persisted at 6-month follow-up.
 These data provide preliminary evidence that
gains in motor function produced by CIMT in
chronic stroke patients may be associated with a
shift in laterality of motor cortical activation toward
the undamaged hemisphere.
Early pioneers who worked on
cortical reorganization

Study Objectives





1. To evaluate the efficacy of CIMT after hemiplegia,
and to study the time period of cortical reorganization
2. To study additional/different cortical reorganization
changes that take place in many chronic hemiplegic
patients
3. To study the efficacy of CIMT and cortical
reorganization in post one year hemiplegia and post
4-5 years of hemiplegia
4. To determine the best time to utilize CIMT
effectively
5. To study whether there is a difference in outcome
because of gender, side of lesion, or age
Hypotheses:

1. There will be a difference in cortical
reorganization after two weeks of CIMT in
post one year and post 4-5 years of
hemiplegia
 2. Cortical reorganization occurs in different
locations depending on chronicity
 3. There will be no difference in functional
outcome and cortical reorganization by:
a). Gender
 b). Side of lesion, i.e. right or left hemiplegia
Study Design

Inclusion Criteria:
 1. Male and female between 40 to 80 years of
age
 2. Willing to to attend two weeks of CIMT
classes
 3. Subject with only one stroke
 4. Upper limb hemiplegia as a result of their
first stroke
 5. Affected limb has > or = to 20 degrees of
wrist extension, and their thumb and at least
2 fingers 10 degrees
Inclusion criteria (cont’d)

6. Minimal spasticity of affected upper
extremity (two or less on Ashworth scale)
 7. Sufficient stability to walk when unaffected
arm is immobilized
 8. Willing to stop the use of the unaffected
good arm at least 90% of waking hours
 9. Ability to perform wheelchair transfers
independently with the unaffected arm
immobilized
 10. Ability to walk 5 feet without an AD
 11. Ability to stand at table/counter without an
AD at least 15-20 minutes
Exclusion criteria






1. Any underlying medical condition that may restrict
the subject to participate in CIMT
2. Conditions that may pose an increased risk for a
second stroke
3. Scheduled elective surgery in the next 6 months
4. Life expectancy less than 3 months
5. Treatment with other investigational
devices/agents within the previous 30 days, or
planned use of other investigational agents or
devices
6. Metal implants in the head, or any movable
fragments in the soft tissue
Exclusion criteria (cont’d)

7. Claustrophobia
 8. Implanted electromechanical devices, such
as cardiac pacemaker or neurostimulator
 9. Possibility of becoming pregnant
 10. Large tattoos/tattooed eyeliner/permanent
cosmetics
 11. MMSE score less than 24
 12. Non-MRI compatible vascular clips, or
endovascular coils
Study Design - BASELINE
 Wolf
Function Test
 MMSE
 Subject’s Health Assessment
Questionnaire
 Finger/hand motor task MRI
Study Design- CIMT
 Total
of ten training sessions over a two
week period
 Each subject required to continue the
given task at home at least 4 hours/day
 Restricted use of unaffected upper
extremity will be achieved by wearing a
resting hand splint during 90% of
waking hours
Two weeks and six months
post CIMT
 Daily
activity log reviewed/collected
 fMRI with tasks
 WMFT
 Health Assessment Questionnaire
 Global Assessment Survey
Time and Events Schedule
Wolf Motor Function Test

Arch Phys Med Rehabil. 2001 Jun;82(6):7505.
 The
reliability of the wolf motor function test
for assessing upper extremity function after
stroke.
Morris DM, Uswatte G, Crago JE, Cook EW 3rd,
Taub E.
Division of Physical Therapy, University of
Alabama, Birmingham
Wolf motor function Reliability
Study
 To
examine the reliability of the Wolf Motor
Function Test (WMFT) for assessing upper
extremity motor function in adults with hemiplegia
 A sample of convenience of 24 subjects with
chronic hemiplegia (onset >1yr), showing
moderate motor impairment
 WMFT includes 15 functional tasks. Performances
were timed and rated by using a 6-point functional
ability scale
 Conclusion - The WMFT is an instrument with high
interrater reliability, internal consistency, test-retest
reliability, and adequate stability
WMFT - Task Items
I can’t take much more!
Results –
 Full
spectrum of results pending.
Results…..so far.

COPM – Canadian Occupational
Performance Measure



COPM is a test for self perceived change in
occupational performance over time.
Test-retest reliability for COPM for performance
and satisfaction is rated at 80% and
89%respectively.
Data was analyzed with standard descriptive
statistics based on performance and
satisfaction at 2 weeks and 6 months post
CIMT.
Results…..so far.

With COPM, 4 out 5 patients demonstrated
increases in both performance and
satisfaction.

Performance



From baseline to 2 weeks- 2.84 to 6.40
Post 6 months - 6.40 to 7.23
Satisfaction


From baseline to 2 weeks- 1.92 to 5.98.
Post 6 months- 5.96 to 7.56
Limitations of Study







Convenience sample precluded randomization
Lack of comparison and control groups
Limited sample size
No blinding procedures
Variable compliance with limb restriction 90% of working hours
A functional task performed at different frequencies appears different on
fMRI – Is change truly a reflection of cortical reorganization or of
variability in frequency?
Isolation of selected functional tasks is difficult


Looking at the fMRI, is cortical reorganization being interpreted for what
may be activation of compensatory muscles?
Does cortical reorganization = neuronal plasticity?
 Do changes in blood flow as measured by fMRI correlate with cortical
reorganization or neuronal plasticity
 Many unaccounted variables which surely contribute to the outcome
 Type of stroke not delineated
 Location of stroke not delineated
 Effect of handedness poorly understood
 Comorbidities and social factors
More Work To Do

The next recruitment phase to begin soon
(two year study)
 NIH more interested in functional outcomes
versus radiological outcomes (initial data had
already established cortical reorganization)
 Plan to make proposal to NIH for functional
outcome study and apply for funding
FIN