A rule-based, dose-finding design for use in stroke rehabilitation research: methodological development.

BACKGROUND: Dose-optimisation studies as precursors to clinical trials are rare in stroke rehabilitation. OBJECTIVE: To develop a rule-based, dose-finding design for stroke rehabilitation research. DESIGN: 3+3 rule-based, dose-finding study. Dose escalation/de-escalation was undertaken according to preset rules and a mathematical sequence (modified Fibonacci sequence). The target starting daily dose was 50 repetitions for the first cohort. Adherence was recorded by an electronic counter. At the end of the 2-week training period, the adherence record indicated dose tolerability (adherence to target dose) and the outcome measure indicated dose benefit (10% increase in motor function). The preset increment/decrease and checking rules were then applied to set the dose for the subsequent cohort. The process was repeated until preset stopping rules were met. PARTICIPANTS: Participants had a mean age of 68 (range 48 to 81) years, and were a mean of 70 (range 9 to 289) months post stroke with moderate upper limb paresis. MODEL TASK: A custom-built model of exercise-based training to enhance ability to open the paretic hand. OUTCOME MEASURE: Repetitions per minute of extension/flexion of paretic digits against resistance. ANALYSIS: Usability of the preset rules and whether the maximally tolerated dose was identifiable. RESULTS: Five cohorts of three participants were involved. Discernibly different doses were set for each subsequent cohort (i.e. 50, 100, 167, 251 and 209 repetitions/day). The maximally tolerated dose for the model training task was 209 repetitions/day. CONCLUSIONS: This dose-finding design is a feasible method for use in stroke rehabilitation research.

Behavioural clusters and predictors of performance during recovery from stroke.

We examined the patterns and variability of recovery post-stroke in multiple behavioral domains. A large cohort of first time stroke patients with heterogeneous lesions was studied prospectively and longitudinally at 1-2 weeks, 3 months and one year post-injury with structural MRI to measure lesion anatomy and in-depth neuropsychological assessment. Impairment was described at all timepoints by a few clusters of correlated deficits. The time course and magnitude of recovery was similar across domains, with change scores largely proportional to the initial deficit and most recovery occurring within the first three months. Damage to specific white matter tracts produced poorer recovery over several domains: attention and superior longitudinal fasciculus II/III, language and posterior arcuate fasciculus, motor and corticospinal tract. Finally, after accounting for the severity of the initial deficit, language and visual memory recovery/outcome was worse with lower education, while the occurrence of multiple deficits negatively impacted attention recovery.

Very Early Constraint-Induced Movement during Stroke Rehabilitation (VECTORS): A single-center RCT.

BACKGROUND: Constraint-induced movement therapy (CIMT) is among the most developed training approaches for motor restoration of the upper extremity (UE). METHODS: Very Early Constraint-Induced Movement during Stroke Rehabilitation (VECTORS) was a single-blind phase II trial of CIMT during acute inpatient rehabilitation comparing traditional UE therapy with dose-matched and high-intensity CIMT protocols. Participants were adaptively randomized on rehabilitation admission, and received 2 weeks of study-related treatments. The primary endpoint was the total Action Research Arm Test (ARAT) score on the more affected side at 90 days after stroke onset. A mixed model analysis was performed. RESULTS: A total of 52 participants (mean age 63.9 +/- 14 years) were randomized 9.65 +/- 4.5 days after onset. Mean NIHSS was 5.3 +/- 1.8; mean total ARAT score was 22.5 +/- 15.6; 77% had ischemic stroke. Groups were equivalent at baseline on all randomization variables. As expected, all groups improved with time on the total ARAT score. There was a significant time x group interaction (F = 3.1, p < 0.01), such that the high intensity CIT group had significantly less improvement at day 90. No significant differences were found between the dose-matched CIMT and control groups at day 90. MRI of a subsample showed no evidence of activity-dependent lesion enlargement. CONCLUSION: Constraint-induced movement therapy (CIMT) was equally as effective but not superior to an equal dose of traditional therapy during inpatient stroke rehabilitation. Higher intensity CIMT resulted in less motor improvement at 90 days, indicating an inverse dose-response relationship. Motor intervention trials should control for dose, and higher doses of motor training cannot be assumed to be more beneficial, particularly early after stroke.

Selective activation of human finger muscles after stroke or amputation.

Individuated finger movements of the human hand require selective activation of particular sets of muscles. Such selective activation is controlled primarily by the motor cortex via the corticospinal tract. Is this selectivity therefore lost when lesions damage the corticospinal tract? Or when the motor cortex reorganizes after amputation? We studied finger movements in normal human subjects and in patients who had recovered substantially from pure motor hemiparesis caused by lacunar strokes, which damage the corticospinal tract without affecting other pathways. Even after substantial recovery from these strokes, individuation of finger movements remained reduced-both for flexion/extension and for adduction/ abduction motion of the fingers. Stroke subjects regained the ability to move the instructed digit through a normal range, but unintentional motion of other digits was increased. This increase did not result from a change in the passive biomechanical coupling of the fingers. Rather, voluntary contractions of muscles that move the intended digit were accompanied by inappropriate contractions in muscles acting on additional digits. These observations suggest that the normal corticospinal system produces individuated finger movements not only by selectively activating certain muscles, but also by suppressing activation of other muscles during voluntary effort to move a given digit. In a separate experiment, reversible amputation of the hand was produced in normal subjects by ischemic nerve block at the wrist. Motor output to the intrinsic muscles and sensory input both become blocked under these conditions, effectively amputating the hand from the nervous system. But the long extrinsic muscles that flex and extend the digits remain normally innervated, and thus flexion forces still can be generated at the fingertips. During reversible amputation of the hand produced by ischemic nerve block, the ability of subjects to activate subdivisions of extrinsic muscles and to exert flexion force at individual fingertips continued to show essentially normal selectivity. Voluntary activation of the remaining muscles thus continues to be selective after amputation, in spite of both the loss of sensory input from the amputated hand, and reorganization within the primary motor cortex. During cortical reorganization after amputation, then, voluntary patterns of motor output intended for finger muscles may not be lost. We therefore examined activity in the stump muscles of above-elbow amputees, who have no remaining hand muscles. Different movements of the phantom hand were accompanied by different patterns of EMG in remaining proximal muscles, distinct from the EMG patterns associated with movement of the phantom elbow. We infer that voluntary motor output patterns that normally control finger movements after amputation may become diverted to remaining proximal muscles.

Additional somatosensory information does not improve cerebellar adaptation during catching.

OBJECTIVE: People with cerebellar damage are impaired in their ability to adapt anticipatory muscle activity during catching. We asked whether prior or on-line information about ball weight and drop height could improve the impaired adaptation of people with cerebellar damage. METHODS: Cerebellar and control subjects caught a series of balls of different weights under two conditions. The first condition provided subjects with information about ball weight prior to the series of trials. The second condition provided subjects with information about ball weight, drop height, and time of ball release during the series of trials. Subjects had to maintain their hand within a vertical spatial 'window' during the catch. We measured 3-dimensional position and electromyography (EMG) from the catching arm. RESULTS: With prior information, controls required a few trials to adapt to a new ball weight. Cerebellar subjects were slow, or unable, to adapt. With on-line information, controls were able to catch the ball within the window immediately, showing that they did not require practice to make this adjustment. Cerebellar subjects remained slow or unable to adapt to the changed ball weight even with on-line information. CONCLUSIONS: These results suggest that other, intact central nervous system structures cannot compensate for the role of the cerebellum in generating and adjusting anticipatory muscle activity across multiple joints.

Inter- and intra-limb generalization of adaptation during catching.

We have previously shown that healthy adults require a few trials to adapt to a changed ball weight during catching. It is not known whether this adaptation generalizes to the opposite arm or to different configurations of the same arm. We tested healthy adult subjects catching balls of different weight while maintaining the hand within a vertical spatial "window." In experiment 1, subjects caught a series of light and heavy balls, first with one hand and then with the other. In experiment 2, subjects caught a series of light and heavy balls, first with the catching arm in either a "bent" or a "straight" configuration and then with the same arm in the other configuration. A percentage transfer value was calculated to determine the degree to which previous experience with a given ball weight in one context affected performance of the same task in a new context (i.e., different arm or different arm configuration). Results showed that generalization occurred both between arms and within an arm. However, the subjects who switched arms showed less generalization than those who switched arm positions. Specifically, the percentage transfer value for subjects who switched arms was 58%, while the percentage transfer for those who switched arm positions was 100%. These results support the idea that the motor system is able to generalize adaptive control of ball catching to the contralateral arm and to different arm configurations. Our findings are also in agreement with the recent notion that multiple internal representations of a task may exist in the CNS. Because there was partial generalization between the two arms, we conclude that there must be a representation stored and used for catching that is not effector specific, but rather can be utilized by brain regions controlling either arm. However, because generalization was only complete within an arm, we conclude that another sensorimotor representation exists, which might only be stored in brain regions specific to a single arm.

Cerebellar subjects show impaired adaptation of anticipatory EMG during catching.

We evaluated the role of the cerebellum in adapting anticipatory muscle activity during a multijointed catching task. Individuals with and without cerebellar damage caught a series of balls of different weights dropped from above. In Experiment 1 (light-heavy-light), each subject was required to catch light balls (baseline phase), heavy balls (adaptation phase), and then light balls again (postadaptation phase). Subjects were not told when the balls would be switched, and they were required to keep their hand within a vertical spatial "window" during the catch. During the series of trials, we measured three-dimensional (3-D) position and electromyogram (EMG) from the catching arm. We modeled the adaptation process using an exponential decay function; this model allowed us to dissociate adaptation from performance variability. Results from the position data show that cerebellar subjects did not adapt or adapted very slowly to the changed ball weight when compared with the control subjects. The cerebellar group required an average of 30.9 +/- 8.7 trials (mean +/- SE) to progress approximately two-thirds of the way through the adaptation compared with 1.7 +/- 0.2 trials for the control group. Only control subjects showed a negative aftereffect indicating storage of the adaptation. No difference in performance variability existed between the two groups. EMG data show that control subjects increased their anticipatory muscle activity in the flexor muscles of the arm to control the momentum of the ball at impact. Cerebellar subjects were unable to differentially increase the anticipatory muscle activity across three joints to perform the task successfully. In Experiment 2 (heavy-light-heavy), we tested to see whether the rate of adaptation changed when adapting to a light ball versus a heavy ball. Subjects caught the heavy balls (baseline phase), the light balls (adaptation phase), and then heavy balls again (postadaptation phase). Comparison of rates of adaptation between Experiment 1 and Experiment 2 showed that the rate of adaptation was unchanged whether adapting to a light ball or a heavy ball. Given these findings, we conclude that the cerebellum is important in generating the appropriate anticipatory muscle activity across multiple muscles and modifying it in response to changing demands though trial-and-error practice.

Comparison of 6- and 7-day physical therapy coverage on length of stay and discharge outcome for individuals with total hip and knee arthroplasty.

Providing physical therapy service on Sundays is a much debated topic among hospital administrators. The purpose of this study was to determine if 7 days per week of physical therapy coverage results in shorter lengths of stay and differing discharge status than 6 days per week. A total of 140 subjects with hip or knee arthroplasty participated; there were 80 in the 6-day groups and 60 in the 7-day groups. Data on postoperative length of stay, discharge destination, and discharge disposition were collected by retrospective medical record review. The Mann-Whitney U test was used to test for differences in length of stay data, and the chi-squared test was used to test for differences in discharge disposition and discharge destination. No significant differences in postoperative length of stay, discharge destination, nor discharge disposition existed between the 6- and 7-day physical therapy coverage hip or knee arthroplasty groups. However, the power of the statistical tests applied was low. This study provides no evidence that 7-day per week physical therapy results in shortened postoperative length of stay, differing discharge destination, nor differing discharge disposition for patients undergoing hip or knee arthroplasty.