Introduction
Many
stroke survivors do not fully recover upper limb function following
stroke, leading to significant disability and diminished quality of
life.
1 Effective treatments are needed for chronic, severely impaired stroke survivors.
2 Other studies showed improved upper limb motor function in chronic stroke for mild/moderately impaired,
3-13
with traditional “constraint induced” treatment studies enrolling only
those with preserved wrist and finger extension (acceptance rate, 10%).
14
However, for those with moderate/severe impairment after stroke,
improvement in function has been more difficult to realize. A recent
study of constraint-induced movement therapy in more severe stroke
reported no clinically significant change in upper limb Fugl-Meyer
assessment scores.
15
Others have also tested the application of technologies and devices, in
moderately/severely impaired chronic stroke survivors, with the
following: functional electrical stimulation (FES),
16-18 sequenced bilateral and unilateral task orientated training,
19 mirror therapy,
20 progressive abduction loading therapy,
21 contralaterally controlled FES,
22 and robotics.
23-27 Limitations included small sample size,
16-18,22-23 lacking control group,
16,23 lacking statistically significant gains on impairment or functional measures,
23 lacking clinically significant change,
20,21,23-25,27 lacking retention of clinically significant gains,
16,19,25,26 or lacking study of retention.
20,23
Furthermore, many studies do not include both a measure of impairment
and an array of actual everyday functional tasks. Our work has focused
on moderately/severely impaired chronic stroke survivors, and in prior
work we developed and tested a protocol that combines technology
applications and motor learning.
28,29
We found clinically and statistically significant gains for those with
moderate/severe stroke considerably beyond that reported by others (eg,
gains in coordination, Fugl-Myer coordination scale [FM], and gains on
the Arm Motor Ability Test [AMAT; 13 complex functional tasks]).
Others
have cited this work stating that “a change in impairment of this
magnitude was previously considered almost impossible in chronic stroke
patients,”
30 and that this is important first evidence for use of high dose neurorehabilitation.
31
Therefore, we considered it important to replicate the administration
of the upper limb motor learning protocol in a follow-on study and again
quantify response. Another consideration was that we had not given
technology a full chance in application to the “whole arm,” that is,
both distal and proximal upper limb regions. Therefore, a first purpose
was to replicate administration of the upper limb motor learning
protocol and to include a treatment group that would receive technology
applications to both distal and proximal limb regions. In addition,
there were 2 important and unanswered questions regarding the dose and
efficacy of this new treatment protocol.
The first question is
whether a shorter treatment duration (ie, <300 hours) could produce
the same degree of recovery, given that the existing protocol was tested
in the paradigm of long-duration dose of 300 hours of therapy.
Therefore, in the current work, we administered the same protocol as in
prior work,
28
and acquired mid-treatment (at 150 hours of treatment) data on the
Fugl-Meyer impairment measure, which underlies complex functional task
performance. We studied whether a mid-treatment plateau occurred or
whether significant recovery occurred in response to the second half of
treatment (mid-treatment to posttreatment).
The second question is
whether the observed gains can be retained after cessation of
treatment. Therefore, we studied retention of gains at 3 months after
treatment ended.
Methods
Study Design
This
was a singleblind, intervention study, stratified using standard
methods, according to the following: (1) impairment level of the upper
limb, in order to equalize impairment across groups and (2) relative
impairment proximal/distal, so one with greater shoulder/elbow
impairment would not be assigned to the group focused on distal
treatment, for example. There were 3 groups, as follows: (1)
distal-focused technology applications group for 30% of treatment time,
(2) proximal-focused technology applications for 30% of treatment time,
and (3) equal proximal and distal technology applications for 30% of
time. The remaining 70% of therapy time within each of the 3 groups was
spent performing functional task practice guided by motor learning
principles. Functional and impairment measures were acquired by a
blinded examiner at pre-, post-treatment and 3-month follow-up (3moF/U),
and the FM impairment measure was acquired also at mid-treatment.
Subjects
Inclusion
criteria included the following: >6 months post single unilateral
stroke; ≥trace muscle contraction, of the affected wrist extensors;
stable medically; no other prior neurological condition; and ability to
follow 2-step commands. The institutional review board provided study
oversight; subjects provided written informed consent.
Intervention
Therapy was implemented 5 hours per day (total), 5 days per week, for 12 weeks.
28
Technology-assist coordination training was 1.5 hours per session, with
content for each group as follows: Distal Group, FES for wrist/hand
muscles (EMS + 2 [Staodyn, Inc, Longmont, CO]; Proximal Group, FES and
robotics for shoulder/elbow muscles/movements (Vectra Pro (Chatanooga
Group, Inc, Hixson, TN) and InMotion2 Shoulder-Elbow-Robot;
InteractiveMotion Technologies, Inc, Cambridge, MA); and Whole Arm
Group, equal proximal and distal applications of technology. The
remainder of each session (3.5 hours/session) consisted of motor
learning of coordinated movements, task component, and full task
practice.
28
Participants
were encouraged to take short rest breaks when their motor performance
degraded; therefore, rest breaks were individualized. Participants were
highly motivated to work hard, but rest periods were important for
productive practice to occur. Also, in the middle of the 5-hour session,
we took a 1-hour lunch break, so the schedule was as follows: 2.5 hours
treatment, 1-hour lunch break, and 2.5 hours of treatment. On average,
participants rested about 15 minutes for every hour of participation.
From
our prior work, we are aware that a 1:3 group therapy paradigm
(therapist:patients) affords several advantages. First, it is less
costly than the 1:1 paradigm, rendering the research more affordable.
Second, participants enjoy the comradery and social aspects of the small
group, and assist each other in numerous ways. Third, with 3
participants in a group, there are always 2 participants working
independently (as set up by the therapist), which is preferable in terms
of learning. The technologies were of some assistance, in that a
participant could be set up with either FES or robotics as a
practice-assist device, freeing up the therapist for that time to work
more closely with another participant. The 1:3 paradigm does require
that the therapist is able to hold in mind simultaneously, the detailed
goals and ability levels of 3 participants and multitask throughout the
entire session. Treatment planning is necessary outside of the patient
treatment sessions. The successful treatment and progression are
dependent on the following: accurate analysis
32 of motor deficits
33; insightful synthesis of multiple, broad, and related factors
34 influencing motor dyscontrol
35; and generalization from known experience and creativity
34 in generating a customized approach to treatment planning and progression, accounting for unique arrays of symptomatology.
35
Overall Principles of Treatment
The
goal of training is recovery of the movement components composing
functional tasks, as well as recovery of performance of the whole
complex task. The motor learning protocol is based first on our clinical
observations that those with moderate/severe impairment are not able to
productively practice complex functional tasks at the beginning of
treatment. Rather, it is important to first treat at the level of
isolated joint movement coordination, if impairment is present at that
level. Some
31 have described this as treatment at the neurophysiological level, which was described early by Brunnstrom,
36 Twitchell,
37 and later by Crow and Harmeling-van der Wel.
38 Krakauer and Carmichael
31
recognize this accurately as different from repetition of task practice
or even task component practice. We organized our treatment according
to the hierarchy given in
Table 1.
The hierarchy begins with training isolated joint movement coordination
of the scapula, shoulder, elbow, forearm, wrist, fingers, and thumb. As
an individual mastered more coordinated motor control of single and/or
multiple joints, we incorporated those movements into functional task
components, and subsequently whole task practice. For each of these
levels of training, we applied the following motor learning principles:
movement practice as close to normal as possible,
39,40 high number of repetitions,
41-44 attention to the motor task,
45 and training specificity.
46
A few examples of practiced task components are reaching, grasp
preparation, and grasp. In order to encourage participation, functional
tasks that were meaningful to the subject were selected from an array of
over 60 tasks (each of which could be divided into task components),
and practiced with supplies and tools that were made readily available.
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Table 1. Upper Limb Training Protocol: Treatment Progression Hierarchy for Coordinated Movement Practice. a
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Table 1. Upper Limb Training Protocol: Treatment Progression Hierarchy for Coordinated Movement Practice.
a
Accurate Selection of the Initial Task Difficulty Is Critical
Prior to assigning a motor task within the motor learning program of
Table 1, performance of motor tasks was assessed for characteristics given in
Table 2. The results of that assessment determined at which point in
Table 1,
the learner should begin for that day, for a given motor task.
Progression of the motor learning program through the hierarchy of
difficulty in
Table 1
was dependent on iterative assessment each day and within each session,
as is the case in clinical neurorehabilitation practice. We followed
the maxim, “test-treat-test.”
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Table 2. Guidelines for Assigning Initial Training Level and Progression of Practice Task.
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Table 2. Guidelines for Assigning Initial Training Level and Progression of Practice Task.
Example
The training provided for the task in
Table 1
(point A) can serve as an example of the finely incrementalized
approach used in this motor learning (ML) protocol 28. For inability to
activate a given muscle in any body position, the first treatment goal
is to facilitate and elicit volitional muscle activation on demand. In a
severely paretic muscle, activation was first elicited within a
synergistic mass pattern, because in our prior work, we found that this
is the easiest condition under which to obtain volitional muscle
activation. For example, we may begin with the subject in the side-lying
position with the involved limb, uppermost, and supported on an
exercise board in the horizontal plane. The limb can be positioned
within a synergistic pattern for the “start” position. The clinician can
provide minimal assistance, gradually withdrawing external manual or
device assistance as soon as the individual begins to regain volitional
control during practice. As the individual recovers the ability to
control muscle activation in this most facilitated position, motor task
practice can be progressed to more difficult body positions.
Treatment
progression occurs in finely incrementalized steps. Some of the methods
used to incrementally support improved performance are as follows:
awareness training of normal and abnormal movements; body position to
mitigate abnormal muscle tone; functional electrical stimulation to
provide sensory feedback regarding muscle activation or to assist in
practice of volitional movements; support of limb segments during
movement practice (eg, either an overhead sling or a shoulder/elbow
robot support of the upper limb); closed-chain motor practice (eg,
weightbearing on palm or forearm) and open-chain motor practice;
isometric, eccentric, and concentric muscle contraction practice;
breakdown of meaningful tasks into separate movement components;
practice of movement accuracy; speed practice; practice of variable
movement directions and variable speed control; and empowerment of the
individual to practice independently.
47
For a number of subjects, there was abnormal soft tissue tightness, in
which case tissue mobilization techniques were employed to stretch
tissue to accommodate more normal active range of movement. For this, we
iteratively stretched and strengthened in small increments in order to
ensure maintenance of lengthened tissue. This type of treatment was
routinely required for scapular/humeral tissue and recovery of more
normal movement patterns. FES and robotics were used as support devices
or movement-assist devices to support practice of more normal movement
patterns.
Measures
We
used the Fugl-Meyer Assessment (FM). A dictionary definition of
coordination is as follows: “the ability to use different parts of the
body together smoothly and efficiently.” This definition inherently
contains a spatial and temporal component. That is, to work together,
movement about joints must be occurring in a correct relative timeframe
for the given movement(s). In the upper limb in some cases, this means
that one joint must be stabilized and held motionless while another
joint movement is executed for the given function. The FM contains items
assessing coordination of upper limb movement of 4 categories as
follows: (1) 15 items (46% of the score) assessing coordination of
single joint movement without interference from other joint muscle
activations, (2) 12 items of movement about more than one joint (36% of
score), (3) trajectory movement execution (9% of the score), and (4)
joint movement in response to a tap or blow (reflex response; 9% of the
score).
48
The FM is considered a hierarchical scale of motor coordination
performance of single and multiple joints, and lays out the pattern of
motor recovery set forth by Brunnstrom,
36 Twitchell,
37 and Crow and Harmeling-van der Wel.
38
As such, the FM is the coordination impairment measure of choice for
the motor learning protocol utilized here, which is based on the
hierarchical progression given in
Table 1. Internationally, the FM is the most widely used measure of coordination in stroke research.
49 For ease of discussion, we will refer to the FM as a measure of coordination.
FM
was obtained at Pre-, mid-, Post-treatment and at 3moF/U. For the most
meaningful results, the FM should be used in conjunction with a measure
of actual functional tasks,
49
which was satisfied in the current study by AMAT, the timed domain
(AMAT-T) and the “function” domain (AMAT-F). The AMAT is a reliable,
valid, and homogeneous measure of 13 actual functional tasks. AMAT is a
“unique standardized measure”, as a homogenous measure of complex
functional tasks, indicating ADL (activities of daily living)
limitation,
50
compared to other measures of functional tasks that include impairment
items (eg, Wolf Motor Function Test) or limit to a few movements rather
than actual functional task performance (eg, Action Research Arm Test).
AMAT is valid across a broad range of impairment levels
50 and is strongly correlated with FM.
51
AMAT time was the time to perform the tasks (AMAT-T; 13 tasks,
timed/summed). The AMAT function domain (AMAT-F) is an ordinal
observational coordination measure (averaged; known minimal clinically
important difference for AMAT-F is 0.44 points
52). Example tasks include ‘use a spoon to scoop up bean” and “unscrew jar lid”).
The Stroke Impact Scale (SIS)
53
was used to assess self-report recovery in a standardized manner. We
calculated the overall score and the domain scores of “Hand” and “Daily
Living,” which were the most germane subscales in the current study.
We
acquired qualitative therapist observational data and subject
self-report data. Therapist observations of changes in impairment and
functional task performance were recorded. Also, we queried the subjects
during the course of their participation. We recorded answers to the
question: Is there anything you can do this week that you were unable to
do at the beginning of the study?
Statistical Analyses
In
study measures, departures from normality were indicated by the QQ plot
and Shapiro-Wilk test of normality, therefore nonparametric methods
were used for analyses. To determine if differences occurred between
groups, we used ordinal regression with group as the factor variable and
the pre-treatment measure as a covariate. For the Fugl-Meyer
coordination test, to determine whether time (baseline, mid-,
posttreatment, and 3moF/U) was significant, we used the nonparametric
Friedman test.
54
Since time was significant, we then conducted further post hoc analysis
to study change over time, using the nonparametric Wilcoxon signed rank
test, and distribution free confidence intervals
55
to determine statistical significance. The same procedure was employed
to identify significant gain between time points in the AMAT-F, AMAT-T,
and SIS measures. The Hochberg procedure was used to correct for
multiple testing (only corrected
P values reported).
Correlations
were calculated using the Spearman method to explore the potential
association between baseline impairment level (FM) and impairment
improvement (FM), as well as between impairment gain (FM) and gain in
functional task performance (AMAT-T and AMAT-F). We generated
descriptive statistics to characterize the baseline, posttreatment, and
gain scores separately for the hemorrhagic and ischemic subjects
Results
Baseline
Table 3
provides baseline subject characteristics. Group assignment was:
Proximal Group (n = 10), Distal Group (n = 8), and Whole Arm Group (n =
18) (
Figure 1, CONSORT study flow diagram).
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Table 3. Baseline Characteristics (n = 36).
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Table 3. Baseline Characteristics (n = 36).
The
unequal sample size across the three groups could have occurred for at
least 2 reasons. First, we conducted a stratification procedure such
that the Whole Group received enrollees from the whole pool of
candidates, whereas each of the other 2 groups were blocked in terms of
receiving subjects with the “wrong” location, respectively, of
impairment in the limb. Second, after stratifying, we used a random
procedure of assigning to the treatment groups. A random procedure does
not always result in equal sample size.
Descriptive Statistics
The
impairment severity distribution across the whole group treated (n =
36), based on initial FM score was as follows: mild, n = 2; moderate, n =
4; severe, n = 30 based on the following ranges: mild = 43-66; moderate
= 29-42; severe = 0-28.
56
There
was an attrition rate of 17% from beginning of enrollment (n = 38) to
follow-up (7/38), which was equally distributed across the 3 groups (3,
2, and 2, respectively). The most frequent reason for leaving the study
at any time point was difficulty with transportation. For this 7-person
subsample, FM change scores ranged from 6 to 18 points with a mean
change of 11.2 points, both comparable to the whole cohort performance.
At
baseline, for hemorrhagic stroke, FM mean was 23.1 (±7.4) and for
ischemic stroke, FM was 22.8 (±10.4), a difference of 0.3 points. At
posttreatment, for hemorrhagic stroke, FM was 33.6 (±10.1) and ischemic
stroke was 32.3 (±12.7), a difference of 1.3 points. The FM mean gain
score was 10.5 points for hemorrhagic stroke and 9.5 points for ischemic
stroke; the difference in gain score was 1 point. These very close
descriptive results indicate no difference in baseline or treatment
response for ischemic versus hemorrhagic stroke.
Group Comparison of Treatment Response: Baseline to 3-Month Follow-up
Treatment Groups
At baseline, there was no difference among the 3 groups on any study measure (
P ≥ .27), age (
P = .85), or time since stroke (
P = .39). There were a significantly greater number of males (n = 15) in the Whole Arm Group (
P = .02). There was no difference across treatment groups in response to treatment according to the AMAT-T (
P = .160), AMAT-F (
P = .33), or FM (
P = .97). Given that there was no significant difference across the 3 groups, we combined the 3 groups (
Table 4) in the study of 2 questions: (1) Was >150 hours of therapy beneficial and (2) Were significant gains retained at follow-up?
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Table 4. FM, AMAT-T, and AMAT-F Organized by Time Point (n = 31).
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Table 4. FM, AMAT-T, and AMAT-F Organized by Time Point (n = 31).
Was
>150 Hours of Therapy Beneficial? Change From Mid-Treatment (150
Hours of treatment) to Posttreatment (300 Hours of Treatment)
We found that there was a statistically and clinically significant improvement from mid- to posttreatment for the FM (
Figure 2;
Table 5a),
indicating an additionally significant improvement (FM improvement =
5.1 points) during the second half of treatment, which extended from 150
to 300 hours of treatment. This “second half” improvement was greater
than the FM improvement of 4.7 points that was observed during the first
half of treatment (from 0 to 150 hours of treatment;
Figure 2;
Table 5a). The total FM improvement, then, from pre- to posttreatment was 9.8 points (
Figure 2), which is double the minimum clinically important difference (MCID) for the FM.
57
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Table 5. Results of Treatment Response.
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Table 5. Results of Treatment Response.
Were Posttreatment Gains Maintained at Follow-up After 3 Months of No Treatment? (Change From Posttreatment to 3moF/U)
For
the FM coordination scale, we found that the significant gains achieved
throughout treatment were maintained three months after cessation of
treatment (
Table 5a; ie, no change from posttreatment to 3moF/U).
For the AMAT-F, we found a clinically and statistically significant improvement in task performance from pre- to posttreatment (
Table 5b). Subsequently, there was additional statistically significant improvement from posttreatment to 3MoFU (
Table 5b;
Figure 3).
For
AMAT-T, we also found a statistically significant improvement in
functional task performance from pretreatment to post-treatment (
Table 5c;
Figure 4). Subsequently, there was additional statistically significant improvement in AMAT-T from posttreatment to 3MoFU (
Table 5c;
Figure 4).
Correlation Analysis
FM baseline was poorly correlated with FM at 3MoFU (
r = 0.37;
P = .04). FM improvement was correlated at the fair level
58 with AMAT-T improvement (
r = 0.50;
P = .0041) and at the good level
58 with AMAT-F improvement (
r = 0.68;
P < .0001).
Multidomain Self-Report Measure
The
SIS self-report measure showed statistically significant improvement in
both subscales of Daily Activities and Hand, as well as the overall SIS
(
P ≤ .016;
Table 6).
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Table 6. Stroke Impact Scale (SIS).
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Table 6. Stroke Impact Scale (SIS).
Qualitative Data
Data on therapist observations showed that subjects made progress in impairment-level upper limb movements (
Supplementary Table SIa). These were captured in the FM measure.
Supplementary Table SIb
contains examples of improved functional tasks and life role
participation activities. These included such things as recovered
self-care, independence in eating, home and community activities and
return to work for 3 individuals
Discussion
First, this is a replication of results from a prior study,
28
in which we obtained impairment and functional task improvement equal
to or beyond clinically significant improvements. In the current study,
our results again showed a magnitude of gains beyond what has been
published, to date. To our knowledge, this study contributes a
first-ever report of 2 important points. First, over 150 hours of
therapy were necessary in this protocol in order to achieve
statistically and clinically significant recovery according to the FM,
at twice the MCID (
Figure 2).
Second, this recovery of coordination was maintained for three months
after the end of therapy, and functional task performance continued to
statistically improve from posttreatment to 3MoFU (
Figures 3 and
4), suggesting further consolidation of the gains in upper limb coordination into improved functional task performance.
Impairment Gains From mid- to Posttreatment Support Benefit of Over 150 Hours of Treatment
The
gain (FM) of 4.7 points from baseline to mid-treatment was clinically
significant. At midpoint, there was no plateau. Rather, there was
subsequent additive statistically and clinically significant improvement
in coordination (FM) from mid- to posttreatment (5.1 points). This is
evidence that as long as treatment was administered, impairment improved
even during treatment throughout weeks 6 to 12. After treatment
cessation, though impairment gains were maintained, the lack of further
gain in impairment suggests that additional neurorehabilitation would be
necessary if further gains in joint movement coordination were to be
realized.
Significant Additional Gains Exhibited in Functional Task Performance for 3 Months After Treatment Cessation
During
the treatment time (pre-/posttreatment), neurorehabilitation produced
statistically (AMAT-T; AMAT-F) and clinically significant (AMAT-F) gains
in functional task performance (
Figures 3 and
4).
This is reasonable, considering coordination is foundational for
functional task performance and coordination also had improved. Notably,
additional statistically significant gains were exhibited in both
AMAT-T and AMAT-F from posttreatment to 3moF/U. That finding along with
the improved coordination (
Figure 2)
continuing up to the posttreatment time point, suggests that the
improvement in joint movement coordination up to that posttreatment time
point may have somewhat preceded subsequent consolidation of
coordination into improved functional task performance during the 3
months between end of treatment and follow-up testing.
Magnitude
of Retained Gains From Pretreatment to 3moF/U: Comparison With Other
Treatment Studies Reporting Retention Results at Follow-up
Chronic Moderate/Severe Impairment Results
In
the current study, retained/improvement (from baseline to after 3
months of no treatment) in coordination was 9.5 points (pretreatment
21.8 points and 3/moFU, 31.3 points;
Table 4,
left panel, first row, n = 31)); this is approximately double the MCID
of 4.25 points, the benchmark for FM clinical significance,
57
and which is greater than that reported by others for patients with
chronic moderate/severe impairment (eg, 3-5 points on the FM).
59-61
Chronic Mild/Moderate Impairment Results
Additionally,
we can compare our results to other studies of chronic stroke but for
those with lesser and more workable mild/moderate impairment. For our
more impaired cohort (severe/moderate), our results were equal to
62 or better than for those with lesser impairment, according to retained improvement.
5,17,63-65 We identified one study of lesser impaired subjects reporting a greater retained gain than our more severe subjects.
66
Chronic Moderate/Severe Functional Task Performance Results
Additionally
supporting high magnitude of retained gains in the current study,
coordination improvement was sufficient to produce retained gains in
functional task performance (AMAT-F; 0.50-point gain) which is greater
than the benchmark for clinically important change (0.44 points),
52 and to our knowledge, not yet reported at this magnitude by others for those with moderate to severe baseline impairment.
Magnitude of Pre-/Posttreatment Gain
Many
studies do not present follow-up results. Therefore, here we include
review of studies with only pre-/post-treatment data. In our cohort, we
had the following severity levels at baseline: severe, n = 30; moderate,
n = 4; and mild n = 2).
56
Impairment
In
the current work, the mean FM score at baseline was 22.88 ± 9.6, which
is considered severe. The mean pre-/posttreatment gain in the current
work was 9.8 (±5.8) points. Baseline impairment level at this severe
level was comparable to our past work for which we used the same
treatment protocol as in the current study; and the results of treatment
are consistent with our prior study, as well.
28,29
For this more severe level of impairment, our results in response to
treatment are almost double that reported by others who studied similar
impairment level (4.7-5.5 FM point gains, respectively).
17,61 For studies of those with greater impairment level than ours, gains ranged from 1.2 to 4.01 FM points,
15,22,24,67 and for studies of more mildly impaired subjects than ours, FM gains ranged from 2 to 14 points.
3,4,6,11,21,27,63,66,68,69
Function
Additionally
supporting high magnitude of pre- to posttreatment gains in the current
work, coordination improvement was sufficient to produce functional
task gains (AMAT-F; 0.46 points), which were equal to or greater than
the benchmark for clinically important change (0.44 points).
52 The qualitative results provide examples of the meaningful nature of these improvements in function and life role activities (
Supplementary Table SIb).
Three participants reported a return to employment; many noted greater
independence in everyday function and return to satisfying leisure
activities. Furthermore, the SIS results indicated significantly greater
activities of daily living and hand function. Taken together, these
results can provide a catalyst to drive change in the way we approach
rehabilitation in the chronic phase of stroke.
This magnitude of
improvement may have been achieved due to the finely incrementalized
approach. For example, the treatment protocol targeted, in part, the
coordination deficits that are assessed with the FM limb-movement items.
Improved FM score indicated progression through the difficulty
hierarchy
38 shown in
Table 1.
Normally coordinated movements are required for normal performance of
daily tasks. For example, simple reaching forward requires extension at
the elbow and flexion at the shoulder, which is considered out of
synergy because one joint is extending while the contiguous joint is
flexing. As these more coordinated movements are achieved, then
components of functional tasks can be performed.
Association of Baseline Impairment Severity to Both Impairment Recovery and Recovery of Functional Task Performance
Relationship of FM Baseline to FM at 3MoF/U
There was poor correlation (
r
= 0.37) between FM baseline and FM gain at 3moF/U. This suggests that
severity of impairment at baseline (FM measure) is not necessarily
linearly associated with ability to respond to treatment according to
that impairment measure. This could have occurred due to either or both
of the factors that may have been operative: weakness and
dyscoordination. Recovery of muscle strength was occurring to some
extent. In fact, others have studied the FM in the acute stage after
stroke and concluded that its variability in assessing recovery may
reflect changes in both strength and coordination.
31
It is certainly a well-known fact that strength is a necessary
requirement for coordinated joint movement. Though strength is
necessary, it is not sufficient; that is, even in the presence of the
required strength, coordination control is still necessary in order to
execute coordinated upper limb movements.
70
Some participants in the current study began with very little active
joint movement, and it was obvious that some strength recovery was
necessary in order to even begin to work on isolated coordination
control. But it was our observation that strength improvement alone did
not result in ability to perform the FM test items or functional
movement components. This is a common clinical finding, as well; that
is, chronic stroke survivors can exhibit the necessary muscle strength,
but inability to perform the coordinated movement normally executed by
that same muscle. As early as 1995, evidence was published quantifying
the clinically known phenomenon of abnormal co-contraction of upper limb
muscles preventing normal coordinated movement after stroke.
71
In our study, we observed that even in the presence of sufficient
muscle strength, further hours of motor practice were required in order
to achieve isolated joint movement control (within and outside of
synergy, without abnormal co-contractions). For that training, we
applied the hierarchy in
Table 1, and we observed incremental improvement that was much slower than would be expected if only strength recovery were operative.
Relationship
between recovery of isolated joint movement coordination (FM gain) and
recovery of functional task performance (AMAT). Improved isolated joint
movement control (FM) was correlated at a “fair” level
58 with AMAT-T gain (
r = 0.50;
P = .004) and more highly correlated with improved AMAT-F gain (
r = 0.68;
P
< .0001). The AMAT-T is a measure of speed of task performance,
which could potentially incorporate compensatory strategies; this
possibility might have resulted in a lower correlation than might have
occurred if all the improvement in AMAT-T occurred as a result of
recovered coordination. In contrast, the AMAT-F is a measure of how
close the task performance is to normal, coordinated movements. The
correlation of
r = 0.68 is a “good” level correlation and
suggests that the improvement in AMAT-F task performance of more
normally coordinated movement components is well-associated with the
improvement in the FM impairment measures of isolated joint movement
control. Taken together with our milestone results in
Tables SIa and SIb,
it is reasonable to consider that there is a relationship between the
following factors: treatment targeted first to isolated joint movement
control and then to task component and task practice; recovery of joint
movement coordination during treatment; measurement of recovery of joint
movement coordination (FM) and recovery of more coordinated functional
task performance (AMAT-F).
Dose
According
to mid- and posttreatment results, the long-dose, high-intensity
treatment was required in order to produce double the clinically
significant impairment gains achieved, which were sufficiently robust to
produce clinically significant functional task performance gains,
greater than previously reported for functional task practice (ie, on
the AMAT). Our results provide evidence supporting benefit of longer
duration, intensive intervention, for the most efficacious outcome.
In other published work, optimal dose for recovery of functional task performance has not been fully elucidated.
14,32
A recent meta-analysis reported a very small dose-response relationship
for those with persistent deficits after stroke, receiving either 57
hours versus 24 hours of intervention.
72
In a recent study, within 32 hours treatment, total repetition numbers
were varied across 4 groups (3200 repetitions, 6400, 9600, or individual
maximum repetitions) for chronic stroke with mild to moderate upper
limb impairment; the reported results stated small, and not clinically
significant change on the primary “function” measure (Action Research
Arm Test) for 2 of 4 groups, and number of repetitions did not affect
change.
73
That study has a detailed companion manual,
74 which provided some means to compare it with the current protocol. There were a number of differences between that study
73 and the current study. First, the dose in the study by Lang et al
73
was much smaller than the current study (32 hours versus 300 hours in
the current study). Second, the subjects in the study by Lang et al
73
were less impaired, having been required to exhibit baseline ability to
open the hand, grasp, and pick up several objects. Third, there was a
statement of no significant change reported in the SIS, whereas in the
current study, we showed a significant improvement in the SIS Hand and
Daily Activities subscales. Fourth, the study by Lang et al
73
described the exercises as follows: “repetitions were compound
movements, including reaching, grasping, manipulating, and releasing.”
In contrast, the current motor learning protocol employed training for
single joint movements and 2-joint movements that were practiced in a
manner to elicit practice as close to a normal movement as possible.
Some level of mastery of these was required before practicing task
components. Fifth, the progression of practice difficulty in the Lang et
al study appears to have been based largely on the number of
repetitions in a timed period and the subject’s perceived fatigue during
performance.
74
In contrast, the current protocol was based first on obtaining a
practice movement that was as close to normal as possible, most often
with some type of assistance in order to achieve practice of a more
coordinated movement. Only with achievement of more coordinated movement
was speed of movement then considered in the treatment. Sixth, there is
a statement in the Lang manual
74
about progression occurring at the point of 90% achievement at their
‘current’ level. In our protocol, we considered advancing to a next
level of difficulty at about 50% of achievement (e.g., of range of
motion, etc). At the initiation of each new motor task, it was generally
not possible to practice a functional task movement that would have
been productive in the sense of being as close to normal as possible.
Thus, our current motor learning protocol may be composed of more finely
incrementalized practice of movements and task components, rendering
them more amenable to finely graded improvements that accumulated over
time and translated to functional task performance improvement. This
difference in practice paradigm could have resulted in the more dramatic
gains in the current study, whereby we showed both clinically and
statistically significant gains on the FM, first at the 150-hour dose,
and then with continued and comparable additive clinically and
statistically significant improvement from mid-treatment (after another
150 hours) to the end of treatment (300 hours dose).
Another study
(constraint-induced movement therapy) reported a gain of 7.4 FM points
in a mild, chronic cohort (n = 13), who received 265 hours of therapy
(1:1 treatment plus constraint-worn hours).
62
Taken together, that cohort study of mild participants plus the current
work for moderate/severely impaired, the 265 to 300 hours of therapy,
respectively, is quite promising. And, in the current work, the
associated functional gains from baseline to 3-month follow-up (eg,
AMAT-F) were 0.58 which is greater than the 0.44 benchmark
52 for clinically significant improvement on the AMAT-F.
Cost/Benefit Considerations
Currently, the average annual cost of yearly rehabilitation for patient with chronic stroke is about $12 000.
1
The question should be about how this money should be spent. Perhaps,
it is not wise to provide low-dose therapies every year that cannot
achieve important functional gains. We need more detailed studies of
cost-efficiency of poststroke rehabilitation to be able to properly
allocate limited resources. In the current study, benefits are first
reflected in improvement of activities of daily living, captured by the
AMAT-F and SIS subscale of Daily Activities. These gains result in less
caregiver need, reducing cost of care. Second, benefits are reflected in
the self-reported recovery of life role participation activities. These
gains result in more family and community involvement, precluding the
isolation that can cause depression and downward spiraling
comorbidities. Third, and potentially most important, this study
presents the discovery that such gains are actually possible in the
chronic stage after stroke. The mechanisms underlying these changes are
largely still unknown. Although in prior work, we found a relationship
between AMAT gain score and changes in task-related brain activation,
according to variables derived from functional magnetic resonance
imaging signal.
75
The current result justifies the additional work that is now needed to
develop cost-efficient therapies. In the meantime, considering financial
cost, we can note that therapy was provided at a 1:3 therapist to
patient ratio. Therefore, the rough cost per patient for 300 hours of
therapy would be $5,000 (based on the following: $50 per hour for 1
therapist or $15,000 per 300 hours of therapy, divided by 3 patients to 1
therapist = $5000 per patient for 300 hours of therapy (based on the
average cost of occupational therapy;
https://health.costhelper.com/occupational-therapy.html#extres2).
Therefore, the cost of our intervention is somewhat less than other
current regular healthcare expenditures. Further tipping the balance are
such events as return to employment as we observed with 3 of our
participants or reduced need of caregiver support with daily activities,
which we observed in a number of participants.
Summary of Likely “Active Ingredients”
Distilling
the evidence presented and discussion points, it is reasonable to
consider that the following are the probable “active ingredients,”
producing the results of the study:
- Accurate initial training level.
- Awareness
training of normal and abnormal movement patterns, which empowers and
motivates the patient to self-monitor and self-progress.
- Training
focused on recovery of the coordination of isolated joint movements and
multiple joint movements, with multiple treatment strategies employed
to support practice of movement as close to normal as possible.
- Accurately titrated progression of treatment.
- Very
finely incrementalized progression of treatment, utilizing an array of
methods to support motor practice as close to normal as possible, and
attention (and celebration) to small goal achievement).
- Clearly stated goals for each small incrementalized practice.
- Incorporation of newly recovered joint movement coordination into task component practice.
- Task and task component selection customized as much as possible to align with the interests and needs of each individual.
- Engagement
of as many strategies as necessary to obtain continued attention and
high repetition practice of coordinated movements.
- Observation and monitoring of inattention or fatigue, and with rest periods held in that case.
- Weekly
team meeting of clinical team in which obstacles to progression are
described and problem solving is offered by team members.
- Periodic team-treatment, whereby another therapist visits the treatment sessions and offers observations and suggestions.
Neha Singh1, 
Nand Kumar
M. V. Padma Srivastava
Amit Mehndiratta
