The work with monkeys described in the previous sections led to a proposal that the process of learned non-use may also occur in humans following acquired injury to the central nervous system (Ostendorf & Wolf, 1981), and that the interventions to overcome learned non-use in deafferented non-human primates may provide avenues to explore recovery in humans.
In transferring the evidence from monkeys to humans, two assumptions have been made: 1) that deafferentation of an UL and stroke are similar in terms of impact on UL function and the
subsequent recovery processes; and 2) that a monkey’s response to injury is similar to a human response.
The pathology of dorsal rhizotomy and stroke are different (Dobkin, 2007; Miltner et al., 1999). Surgical deafferentation of an UL produces a specific and controlled lesion of the spinal nerve root, affecting a defined area and removing sensation input from that limb. Stroke in comparison produces a diffuse, variable central lesion, affecting many functional areas of the brain (Dobkin, 2007). Stroke may impact on the sensation of an UL, but this would not usually result in the complete hemi-anaesthesia which is inevitable in the limb supplied by the deafferented nerves. In addition, following stroke, it is likely that there will be damaged efferent pathways leading to motor control impairments (Taub & Wolf, 1997). There may also be cognitive impairments (Dobkin, 2007; Intercollegiate Stroke Working Party, 2012) and emotional changes
(Intercollegiate Stroke Working Party, 2012). In stroke, the lesion occurs in the brain rather than at spinal cord level, so the ‘shock’ that occurs is likely to be different. For these reasons, it is
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unlikely that learned non-use is the only mechanism impacting on motor control following stroke. It has been proposed (Sterr et al., 2002b; Taub et al., 2006b) that learned non-use is different to both motor neglect, the underutilisation of a body part in the absence of paralysis or primary sensory deficit (Sampanis & Riddoch, 2013, p. 110) and to unilateral spatial neglect, a failure “to report, respond, or orient to novel or meaningful stimuli presented to the side opposite a brain lesion” (Heilman et al., 1993, p. 279). This proposition is based on evidence that motor neglect tends to reduce over time (Sampanis & Riddoch, 2013), whilst learned non-use is likely to become more marked (Sterr et al., 2002b), and that unilateral spatial neglect occurs more frequently with a right-sided lesion (Gialanella & Ferlucci, 2010), whilst learned non-use occurs equally with right and left sided lesions (Sterr et al., 2002b). Whilst it may be a separate mechanism, there is currently no means of identifying learned non-use in stroke survivors (Dobkin, 2007; van der Lee, 2001); it is, therefore, not yet possible to explore the relationship between learned non-use and recovery following stroke in humans.
The first study with a human participant (Ostendorf & Wolf, 1981) tested the concept of constraining (in a shoulder sling worn throughout the day) the ipsilesional limb of a 50 year old woman, 18 months post-stroke, with UL paresis, described as presenting with isolated movement at shoulder, elbow, wrist and fingers, but with a dominance of synergy in functional movements.
Descriptions of non-human primate research use the term ‘restraint’ to describe the
immobilisation of a limb. The term reflects that there was neither collaboration with, nor choice available to, the participants in these studies. Once the research was transferred to humans the term ‘constraint’ has been used to reflect the active participation and the collaboration that occurs between the intervention provider and the stroke survivor (Russo, 1995). In this first study (Ostendorf & Wolf, 1981), a constraint sling was worn throughout the day during the intervention B-phase of an A-B-A quasi-experimental single system study (Ottenbacher, 1990), where each
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phase lasted for seven days. Where an intervention comprises only constraint of the limb with no specified additional training, as in this study, it has been termed forced-use (Eugster-Buesch et al., 2012; Fuzaro et al., 2012; Pierce et al., 2003; Ploughman & Corbett, 2004). The study found an increase in participant-reported frequency of purposeful UL behaviours from a pre-defined list. It was unclear how these reports were rated and clinical significance of this finding was not
discussed. A qualitative improvement in ability to use the contralesional hand to write name and use an iron were also reported. The functional assessment, a non-validated tool based on a protocol from Emory University Research and Teaching Center included 18 tasks such as moving hand from lap to table, straightening elbow, picking up cup, paper clip and pencil. These were timed and the video-recordings of the tasks were rated by blinded assessors for quality of
movement on a 0-5 scale, where ‘0’ was allocated for ‘no visible movement of affected extremity’ and ‘5’ was allocated for ‘isolated movements throughout the limb, but may be weak or
uncoordinated’. The total time to complete all tasks reduced over the duration of the study; however, the biggest reduction in time was from day one of the baseline in Phase A to day seven in baseline Phase A, therefore the majority of the reduction occurred prior to the intervention phase, which indicated the reduction in time was likely to be a result of a practice effect. Quality of the movement did not change. The use of a non-validated functional assessment, the limited detail of the processes to establish the reliability of the reported purposeful UL behaviours, and the lack of blinding of the assessor to the phases indicate a number of potential sources of bias in this study.
In a larger study, (Wolf et al., 1989) studied the effects of forced-use with a sling constraint, which enclosed the fingers of the ipsilateral UL, over a period of two weeks in 25 chronic (greater than one year post-insult) stroke and head-injured participants, who had active finger and wrist extension. The participants wore the constraint for the majority of their waking hours. The study was not controlled, although, six once-weekly baseline measurements indicated that the
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participants’ UL function was stable prior to the forced-use. The measurements comprised 21 non-validated tasks which were similar, but not identical, to those used in the previous study; additions included lifting a basket and writing own name. The test was subsequently named the Emory Motor Function Test (Taub et al., 1993). Time taken to complete each task was measured and quality of movement was rated by blinded assessors observing the video-recordings and marking a non-validated matrix to indicate the presence or absence of isolated or synergistic movement for each task. Findings were only reported for the 21 participants (stroke n=16; head- injury n=5) who completed all measures. At post-intervention, compared to baseline, there was a statistically significant decreased median change time in 8 of the 21 upper limb functional tasks (p<0.05 for each of the 8 tasks). This increased to 19 out of 21 tasks at 4 months post-
intervention (p<0.05 for each of the 19 tasks); these findings were maintained at one year post- stroke. There was no change in the quality of movement over time. This indicated that forced- use may have potential for reducing the time taken to complete UL tasks, and that this benefit may continue after the intervention is complete; however, as there was no control group there is a risk that changes may have been due to variables other than the intervention and that the same change may have occurred without the sling constraint. In addition, participants not completing all the measures were excluded and a non-validated measure of functional tasks was used; these may have impacted on the internal validity of the study.
Based on the work to overcome learned non-use in monkeys, described in section 2.1.2, Taub et al. (1993) introduced a training element to the forced-use intervention, developing what is now recognised as the original CIMT protocol, sometimes referred to as the signature CIMT protocol (Taub et al., 1999). In a small, randomised, controlled study of chronic stroke survivors, CIMT (n=4) was compared to an attention comparison (n=5). The two week CIMT intervention comprised six hours training of the contralesional UL each weekday and the wearing a of a constraint on the ipsilesional UL for 90% of waking hours, allowing for a small allocation of time
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without the constraint to undertake washing and toileting. The training included activities such as using cutlery, playing games and writing (Taub et al., 1993). The participants in the attention comparison: a) were told that they had greater ability in their ipsilateral UL; b) undertook two therapy sessions in which passive range of motion (ROM) and sensory loss were assessed; and c) undertook self-initiated ROM exercises for 15 minutes each day. Taub et al. (1993) reported that the participants in the CIMT group each had statistical significant or near significant reductions (nonparametric sign test, p<0.06) in mean performance times in Emory Motor Function Test (EMFT) (Wolf et al., 1989) and The Arm Motor Activity Test (AMAT), a test of activities involving the UL (McCulloch et al., 1988). This was not the case in the comparison group (p>0.3). Functional ability, rated by assessors blinded to group allocation, was also reported as significantly increased on both EMFT and AMAT for all participants in the CIMT group, but not for the comparison group; however the statistics to support this were not presented. Whilst the study indicates that CIMT may be beneficial when compared to an attention comparison of less than six hours, the
interpretation of the measures is limited by a lack of reporting of the findings and the use of non- validated measures without an established Minimal Clinically Important Difference (MCID). A MCID is important as it indicates the smallest amount of change from an intervention that would be interpreted as important by a participant or patient (McGlothlin & Lewis, 2014), thereby indicating that change below this level would not be meaningful. In addition, the small sample size and a lack of detail of the randomisation procedures may have introduced bias. Whilst there was a clear need for further investigation of the intervention, the components of constraint and training described in this study continue to define CIMT.
Van der Lee et al. (1999) reported an observer-blinded RCT (N=66) of what was nominally forced- use, in chronic (greater than one year post stroke) stroke survivors. The experimental
intervention comprised constraint of the ipsilesional UL for 12 consecutive days, excluding travelling, sleeping and self-care activities, in addition to six hours of training, five days a week for
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12 days. Due to the inclusion of a training component, the intervention meets the definition of CIMT being used in this thesis. The comparison group undertook six hours of UL therapy according to neurodevelopmental theory, tasks were completed bimanually, and, where
required, the ipsilesional UL was used to assist the contralesional UL. The training for both groups consisted of housekeeping activities, handicrafts and games, but the content of the sessions is not described. A mean difference in gain on the Action Research Arm Test (ARAT) in favour of the experimental group of 3.0 points (95% CI 1.3 to 4.8, p<0.05) was found; this gain was maintained at one year. The gain of 3.0 is, however, less than the ARAT MCID of 12 for the dominant hand and 17 for the non-dominant UL (Lang et al., 2008).
Van der Lee et al. (1999) also found a significant differential effect of treatment on the Action Research Arm Test (ARAT) in participants with sensory disorder and those without (F3,168=5.95, p=0.0001). The mean improvement on the ARAT for the participants with sensory disorder (assessed by short non-standardised clinical assessment) (n=16) and receiving the experimental intervention was 6.7 points greater than participants without sensory disorder (n=11) receiving the comparison intervention, exceeding the MCID for the ARAT. They also found the Motor Activity Log Amount of Use rating (MAL AOU), a semi-structured interview to measure real life use of the UL (Taub et al., 1993) with established validity and reliability in stroke survivors (Uswatte et al., 2005; van der Lee et al., 2004), showed unilateral spatial neglect (assessed by cancellation and line bisection tests) to have a differential effect on treatment (F3,165=4.93, p=0.003). The mean improvement of participants with unilateral spatial neglect (n=3) receiving the experimental intervention was 1.16 points higher (exceeding the MCID) than that of
participants with unilateral spatial neglect in the comparison group, although this effect was lost at one year follow-up. Further study of sub-groups is necessary, firstly to identify sub-groups that may respond differentially in RCTs potentially leading to a type II error (Sim & Wright, 2000, p.
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205), and secondly, to assist therapists in deciding which stroke survivors are likely to benefit from, and therefore should be offered, CIMT.
Section 2.1 indicates that CIMT does have an established theoretical basis, as demanded by the development-evaluation-implementation process, although there are, as discussed, challenges in transferring this theoretical basis from monkeys to humans. The original protocol has been defined, but there is a need to explore which stroke survivors are likely to benefit from CIMT.