Gitendra Uswatte

New treatments in neurorehabilitation founded on basic research.

Recent discoveries about how the central nervous system responds to injury and how patients reacquire lost behaviours by training have yielded promising new therapies for neurorehabilitation. Until recently, this field had been largely static, but the current melding of basic behavioural science with neuroscience promises entirely new approaches to improving behavioural, perceptual and cognitive capabilities after neurological damage. Studies of phenomena such as cortical reorganization after a lesion, central nervous system repair, and the substantial enhancement of extremity use and linguistic function by behavioural therapy, support this emerging view. The ongoing changes in rehabilitation strategies might well amount to an impending paradigm shift in this field.

A Placebo-Controlled Trial of Constraint-Induced Movement Therapy for Upper Extremity After Stroke

Background and Purpose— Constraint-Induced Movement therapy (CI therapy) is a neurorehabilitation technique developed to improve use of the more affected upper extremity after stroke. A number of studies have reported positive effects for this intervention, but an experiment with a credible placebo control group has not yet been published. Methods— We conducted a placebo-controlled trial of CI therapy in patients with mild to moderate chronic (mean=4.5 years after stroke) motor deficit after stroke. The CI therapy group received intensive training (shaping) of the more affected upper extremity for 6 hours per day on 10 consecutive weekdays, restraint of the less affected extremity for a target of 90% of waking hours during the 2-week treatment period, and application of a number of other techniques designed to produce transfer to the life situation. The placebo group received a program of physical fitness, cognitive, and relaxation exercises for the same length of time and with the same amount of therapist interaction as the experimental group. Results— After CI therapy, patients showed large (Wolf Motor Function Test) to very large improvements in the functional use of their more affected arm in their daily lives (Motor Activity Log; P<0.0001). The changes persisted over the 2 years tested. Placebo subjects showed no significant changes. Conclusion— The results support the efficacy of CI therapy for rehabilitating upper extremity motor function in patients with chronic stroke.

Reliability and Validity of the Upper-Extremity Motor Activity Log-14 for Measuring Real-World Arm Use

Background and Purpose— In research on Constraint-Induced Movement (CI) therapy, a structured interview, the Motor Activity Log (MAL), is used to assess how stroke survivors use their more-impaired arm outside the laboratory. This article examines the psychometrics of the 14-item version of this instrument in 2 chronic stroke samples with mild-to-moderate upper-extremity hemiparesis. Methods— Participants (n=41) in the first study completed MALs before and after CI therapy or a placebo control procedure. In addition, caregivers independently completed a MAL on the participants. Participants (n=27) in the second study completed MALs and wore accelerometers that monitored their arm movements for 3 days outside the laboratory before and after an automated form of CI therapy. Results— Validity of the participant MAL Quality of Movement (QOM) scale was supported. Correlations between pretreatment-to-posttreatment change scores on the participant QOM scale and caregiver MAL QOM scale, caregiver MAL amount of use (AOU) scale, and accelerometer recordings were 0.70, 0.73, and 0.91 (P<0.01), respectively. Internal consistency (α>0.81), test–retest reliability (r>0.91), stability, and responsiveness (ratio >3) of the participant QOM scale were also supported. The participant AOU and caregiver QOM and AOU scales were internally consistent, stable, and sensitive, but were not reliable. Conclusions— The participant MAL QOM scale can be used exclusively to reliably and validly measure real-world, upper-extremity rehabilitation outcome and functional status in chronic stroke patients with mild-to-moderate hemiparesis.

The Motor Activity Log-28 Assessing daily use of the hemiparetic arm after stroke

Background: Data from monkeys with deafferented forelimbs and humans after stroke indicate that tests of the motor capacity of impaired extremities can overestimate their spontaneous use. Before the Motor Activity Log (MAL) was developed, no instruments assessed spontaneous use of a hemiparetic arm outside the treatment setting. Objective: To study the MAL’s reliability and validity for assessing real-world quality of movement (QOM scale) and amount of use (AOU scale) of the hemiparetic arm in stroke survivors. Methods: Participants in a multisite clinical trial completed a 30-item MAL before and after treatment (n = 106) or an equivalent no-treatment period (n = 116). Participants also completed the Stroke Impact Scale (SIS) and wore accelerometers that monitored arm movement for three consecutive days outside the laboratory. All were 3 to 12 months post-stroke and had mild to moderate paresis of an upper extremity. Results: After an item analysis, two MAL tasks were eliminated. Revised participant MAL QOM scores were reliable (r =0.82). Validity was also supported. During the first observation period, the correlation between QOM and SIS Hand Function scale scores was 0.72. The corresponding correlation for QOM and accelerometry values was 0.52. Participant QOM and AOU scores were highly correlated (r = 0.92). Conclusions: The participant Motor Activity Log is reliable and valid in individuals with subacute stroke. It might be employed to assess the real-world effects of upper extremity neurorehabilitation and detect deficits in spontaneous use of the hemiparetic arm in daily life.

Remodeling the Brain. Plastic Structural Brain Changes Produced by Different Motor Therapies After Stroke

Background and Purpose— Studies on adult stroke patients have demonstrated functional changes in cortical excitability, metabolic rate, or blood flow after motor therapy, measures that can fluctuate rapidly over time. This study evaluated whether evidence could also be found for structural brain changes during an efficacious rehabilitation program. Methods— Chronic stroke patients were randomly assigned to receive either constraint-induced movement therapy (n=16) or a comparison therapy (n=20). Longitudinal voxel-based morphometry was performed on structural MRI scans obtained immediately before and after patients received therapy. Results— The group receiving constraint-induced movement therapy exhibited far greater improvement in use of the more affected arm in the life situation than the comparison therapy group. Structural brain changes paralleled these improvements in spontaneous use of the more impaired arm for activities of daily living. There were profuse increases in gray matter in sensory and motor areas both contralateral and ipsilateral to the affected arm that were bilaterally symmetrical, as well as bilaterally in the hippocampus. In contrast, the comparison therapy group failed to show gray matter increases. Importantly, the magnitude of the observed gray matter increases was significantly correlated with amount of improvement in real-world arm use. Conclusions— These findings suggest that a previously overlooked type of brain plasticity, structural remodeling of the human brain, is harnessed by constraint-induced movement therapy for a condition once thought to be refractory to treatment: motor deficit in chronic stroke patients.

Retention of upper limb function in stroke survivors who have received constraint-induced movement therapy: the EXCITE randomised trial

BACKGROUND The aim of constraint-induced movement therapy (CIMT) is to promote use of a limb that is functionally impaired after a stroke. In one form of CIMT to treat upper limb impairment, use of the less severely affected arm is restricted for many hours each weekday over 2 consecutive weeks. The EXCITE trial has previously shown the efficacy of this intervention for patients 3-9 months poststroke who were followed-up for the next 12 months. We assessed the retention of improvements 24 months after the intervention. METHODS In the EXCITE trial, 106 of 222 participants who had mild to moderate poststroke impairments were randomly assigned to receive CIMT rather than usual and customary care. We assessed this group of patients every 4 months for the primary outcome measure of impaired upper limb function, as measured with the Wolf motor function test (WMFT) and the motor activity log (MAL). Health-related quality of life, measured with the stroke impact scale (SIS), was a secondary outcome measure. Analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT00057018. FINDINGS The effects at 24 months after treatment did not decline from those at 12 months for time taken to complete the WMFT (-0.32 s, 95% CI -3.70 to 3.06), for weight lifted in the WMFT (-1.39 kg, -2.74 to -0.04), for WMFT grip strength (-4.39 kg, -6.91 to -1.86), for amount of use in the MAL (-0.17, -0.38 to 0.04), or for how well the limb was used in the MAL (-0.14, -0.34 to 0.06). The additional changes were in the direction of increased therapeutic effect. For the strength components of the WMFT, p<0.0001. INTERPRETATION Patients who have mild to moderate impairments 3-9 months poststroke have substantial improvement in functional use of the paretic upper limb and quality of life 2 years after a 2-week CIMT intervention. Thus, this intervention has persistent benefits.

Methods for a Multisite Randomized Trial to Investigate the Effect of Constraint-Induced Movement Therapy in Improving Upper Extremity Function among Adults Recovering from a Cerebrovascular Stroke

This article describes the study design, methodological considerations, and demographic characteristics of a phase III RCT to determine if 1) constraint-induced therapy (CI therapy) can be applied with therapeutic success 3 to 9 months after stroke across different sites, 2) gains that might occur persist over 2 years, 3) initial level of motor ability determines responsiveness to CI therapy, and 4) the treatment effect differs between those treated before 9 months and after 1 year. Six sites will screen and recruit poststroke survivors stratified on initial level of motor ability and after randomization allocate participants to immediate or delayed intervention. Primary outcomes include a laboratory-based measure of function (Wolf Motor Function Test [WMFT]) and a real-world participant-centered functional use measure (Motor Activity Log [MAL]). Secondary outcomes concern function, behavior, and compliance. This is the first multisite, single-blind RCT of a formal training intervention for upper extremity rehabilitation in subacute stroke in the United States.

Objective Measurement of Functional Upper-Extremity Movement Using Accelerometer Recordings Transformed With a Threshold Filter

BACKGROUND AND PURPOSE The consensus is that the most important outcome for rehabilitation is functional activity in the life situation. Constraint-Induced Movement Therapy, a new treatment that transfers in-clinic gains to the life situation, demands objective measurement of real-world movement. However, direct, objective, and accurate measures of arm use in the real world are not available. Previous attempts to use accelerometry to measure extremity movement have failed because of unacceptable variability. This problem has been addressed here by use of a threshold filter. METHODS Nine stroke patients and 1 healthy individual wearing accelerometers were videotaped while they carried out their usual activities at home or in the clinic; the duration of their arm, torso, and ambulatory movements was judged by 2 observation teams. In addition, 11 college students performed 5 standardized activities of daily living for varying durations in the laboratory. The accelerometer data were transformed; the raw value recorded for a given epoch was set to a constant if it exceeded a low threshold. RESULTS The threshold-filtered recordings measured the duration of movement accurately and with very little variability. Correlations between the threshold-filtered recordings and the observer ratings of the duration of arm, torso, and ambulatory movements were 0.93, 0.93 and 0.99, respectively; the corresponding correlations for the raw values were -0.17, 0.34, and 0.85. CONCLUSIONS These results present initial evidence for the validity of threshold-filtered accelerometer recordings for objectively measuring the amount of real-world upper-extremity movement as an index of treatment outcome for rehabilitation patients.

The EXCITE Stroke Trial Comparing Early and Delayed Constraint-Induced Movement Therapy

Background and Purpose— Although constraint-induced movement therapy (CIMT) has been shown to improve upper extremity function in stroke survivors at both early and late stages after stroke, the comparison between participants within the same cohort but receiving the intervention at different time points has not been undertaken. Therefore, the purpose of this study was to compare functional improvements between stroke participants randomized to receive this intervention within 3 to 9 months (early group) to participants randomized on recruitment to receive the identical intervention 15 to 21 months after stroke (delayed group). Methods— Two weeks of CIMT was delivered to participants immediately after randomization (early group) or 1 year later (delayed group). Evaluators blinded to group designation administered primary (Wolf Motor Function Test, Motor Activity Log) and secondary (Stroke Impact Scale) outcome measures among the 106 early participants and 86 delayed participants before delivery of CIMT, 2 weeks thereafter, and 4, 8, and 12 months later. Results— Although both groups showed significant improvements from pretreatment to 12 months after treatment, the earlier CIMT group showed greater improvement than the delayed CIMT group in Wolf Motor Function Test Performance Time and the Motor Activity Log (P<0.0001), as well as in Stroke Impact Scale Hand and Activities domains (P<0.0009 and 0.0214, respectively). Early and delayed group comparison of scores on these measures 24 months after enrollment showed no statistically significant differences between groups. Conclusions— CIMT can be delivered to eligible patients 3 to 9 months or 15 to 21 months after stroke. Both patient groups achieved approximately the same level of significant arm motor function 24 months after enrollment. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00057018.

AutoCITE: Automated Delivery of CI Therapy With Reduced Effort by Therapists

Background and Purpose— To evaluate the effectiveness of a device that automates Constraint-Induced Movement therapy (CI therapy), termed AutoCITE, when only partially supervised by therapists. Methods— Twenty-seven participants with chronic stroke trained with AutoCITE for 3 hours per day for 10 consecutive weekdays. Participants were assigned to 1 of 3 groups in a fixed irregular order (ie, in alternating blocks): supervision from a therapist for 100%, 50%, or 25% of training time. Results— The effect sizes of the treatment gains for the 3 groups on the Motor Activity Log (MAL) were very large and for the Wolf Motor Function Test they were large (all P<0.001) but were not significantly different from one another. Gains were comparable to those previously reported for participants who received an equal amount of standard one-on-one CI therapy without the device. At 1-month and long-term follow-up, gains from pretreatment on the MAL were also significant (P<0.001). Conclusion— These results demonstrate that AutoCITE training with greatly reduced supervision from a therapist is as effective as standard one-on-one CI therapy.