Deborah S. Nichols-Larsen

Factors Influencing Stroke Survivors’ Quality of Life During Subacute Recovery

Background and Purpose— Health-related quality of life (HRQOL) is an important index of outcome after stroke and may facilitate a broader description of stroke recovery. This study examined the relationship of individual and clinical characteristics to HRQOL in stroke survivors with mild to moderate stroke during subacute recovery. Methods— Two hundred twenty-nine participants 3 to 9 months poststroke were enrolled in a national multisite clinical trial (Extremity Constraint-Induced Therapy Evaluation). HRQOL was assessed using the Stroke Impact Scale (SIS), Version 3.0. The Wolf Motor Function Test documented functional recovery of the hemiplegic upper extremity. Multiple analysis of variance and regression models examined the influence of demographic and clinical variables across SIS domains. Results— Age, gender, education level, stroke type, concordance (paretic arm=dominant hand), upper extremity motor function (Wolf Motor Function Test), and comorbidities were associated across SIS domains. Poorer HRQOL in the physical domain was associated with age, nonwhite race, more comorbidities, and reduced upper-extremity function. Stroke survivors with more comorbidities reported poorer HRQOL in the area of memory and thinking, and those with an ischemic stroke and concordance reported poorer communication. Conclusions— Although results may not generalize to lower functioning stroke survivors, individual characteristics of persons with mild to moderate stroke may be important to consider in developing comprehensive, targeted interventions designed to maximize recovery and improve HRQOL.

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.

Constraint-induced movement therapy results in increased motor map area in subjects 3 to 9 months after stroke.

Background. Constraint-induced movement therapy (CIMT) has received considerable attention as an intervention to enhance motor recovery and cortical reorganization after stroke. Objective. The present study represents the first multi-center effort to measure cortical reorganization induced by CIMT in subjects who are in the subacute stage of recovery. Methods. A total of 30 stroke subjects in the subacute phase (>3 and <9 months poststroke) were recruited and randomized into experimental (receiving CIMT immediately after baseline evaluation) and control (receiving CIMT after 4 months) groups. Each subject was evaluated using transcranial magnetic stimulation (TMS) at baseline, 2 weeks after baseline, and at 4-month follow-up (ie, after CIMT in the experimental groups and before CIMT in the control groups). The primary clinical outcome measure was the Wolf Motor Function Test. Results. Both experimental and control groups demonstrated improved hand motor function 2 weeks after baseline. The experimental group showed significantly greater improvement in grip force after the intervention and at follow-up (P = .049). After adjusting for the baseline measures, the experimental group had an increase in the TMS motor map area compared with the control group over a 4-month period; this increase was of borderline significance (P = .053). Conclusions. Among subjects who had a stroke within the previous 3 to 9 months, CIMT produced statistically significant and clinically relevant improvements in arm motor function that persisted for at least 4 months. The corresponding enlargement of TMS motor maps, similar to that found in earlier studies of chronic stroke subjects, appears to play an important role in CIMT-dependent plasticity.

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.

The EXCITE Trial: Predicting a clinically meaningful motor activity log outcome.

Background and Objective . This study determined which baseline clinical measurements best predicted a predefined clinically meaningful outcome on the Motor Activity Log (MAL) and developed a predictive multivariate model to determine outcome after 2 weeks of constraint-induced movement therapy (CIMT) and 12 months later using the database from participants in the Extremity Constraint Induced Therapy Evaluation (EXCITE) Trial. Methods. A clinically meaningful CIMT outcome was defined as achieving higher than 3 on the MAL Quality of Movement (QOM) scale. Predictive variables included baseline MAL, Wolf Motor Function Test (WMFT), the sensory and motor portion of the Fugl-Meyer Assessment (FMA), spasticity, visual perception, age, gender, type of stroke, concordance, and time after stroke. Significant predictors identified by univariate analysis were used to develop the multivariate model. Predictive equations were generated and odds ratios for predictors were calculated from the multivariate model. Results. Pretreatment motor function measured by MAL QOM, WMFT, and FMA were significantly associated with outcome immediately after CIMT. Pretreatment MAL QOM, WMFT, proprioception, and age were significantly associated with outcome after 12 months. Each unit of higher pretreatment MAL QOM score and each unit of faster pretreatment WMFT log mean time improved the probability of achieving a clinically meaningful outcome by 7 and 3 times at posttreatment, and 5 and 2 times after 12 months, respectively. Patients with impaired proprioception had a 20% probability of achieving a clinically meaningful outcome compared with those with intact proprioception. Conclusions. Baseline clinical measures of motor and sensory function can be used to predict a clinically meaningful outcome after CIMT.

Measurement structure of the Wolf Motor Function Test: implications for motor control theory.

Background. Tools chosen to measure poststroke upper-extremity rehabilitation outcomes must match contemporary theoretical expectations of motor deficit and recovery because an assessment’s theoretical underpinning forms the conceptual basis for interpreting its score. Objective. The purpose of this study was to investigate the theoretical framework of the Wolf Motor Function Test (WMFT) by (1) determining whether all items measured a single underlying trait and (2) examining the congruency between the hypothesized and the empirically determined item difficulty orders. Methods. Confirmatory factor analysis (CFA) and Rasch analysis were applied to existing WMFT Functional Ability Rating Scale data from 189 participants in the EXCITE (Extremity Constraint-Induced Therapy Evaluation) trial. Fit of a 1-factor CFA model (all items) was compared with the fit of a 2-factor CFA model (factors defined according to item object-grasp requirements) with fit indices, model comparison test, and interfactor correlations. Results. One item was missing sufficient data and therefore removed from analysis. CFA fit indices and the model-comparison test suggested that both models fit equally well. The 2-factor model yielded a strong interfactor correlation, and 13 of 14 items fit the Rasch model. The Rasch item difficulty order was consistent with the hypothesized item difficulty order. Conclusion. The results suggest that WMFT items measure a single construct. Furthermore, the results depict an item difficulty hierarchy that may advance the theoretical discussion of the person ability versus task difficulty interaction during stroke recovery.

Can the Wolf Motor Function Test Be Streamlined

Background. To assess upper extremity (UE) capabilities following stroke, the Wolf Motor Function Test (WMFT) measures time to complete 15 UE tasks and 2 strength tasks, but takes 30 to 45 minutes for the clinician to complete. Objective. In an effort to streamline the WMFT, this study evaluated the association between the magnitude of improvement on any timed task of the WMFT and the change score on all other tasks among participants in the Extremity Constraint Induced Therapy Evaluation (EXCITE) trial. Methods. This association was evaluated using regression methods according to chronicity and controlling for key covariates (functional level, gender, concordance) for log mean WMFT scores. Results. After controlling for covariates, 6 tasks (hand to table [front], hand to box [front], reach and retrieve, lift can, lift pencil, and fold towel) influenced the overall WMFT score for survivors meeting EXCITE criteria and treated within 3 to 9 months poststroke. Six different tasks (extend elbow weight, hand to box [front], lift can, lift pencil, turn key in lock, and fold towel) influenced the overall WMFT score for those receiving constraint-induced movement therapy (CIMT) 1 year later. The importance of certain tasks relative to others may best represent overall UE function, but this streamlining enables the clinician to prioritize these tasks in the evaluation. Conclusions. The delineation of those tasks depends on the time poststroke from enrollment to CIMT. This study demonstrates that the WMFT can be streamlined from 17 to 6 tasks.

Looking in the Rear View Mirror When Conversing With Back Seat Drivers: The EXCITE Trial Revisited

The initial Point of View: Directions for Research (Neurorehabilitation and Neural Repair, 2007;21:3-13) identified confounders that might limit the impact that rehabilitation multicenter clinical trials may have upon altering practice patterns. Part of that viewpoint addressed the Extremity Constraint Induced Therapy Evaluation (EXCITE) Trial and highlighted some of its perceived strengths and limitations. The present Point of View expands upon factors worthy of consideration in planning and executing clinical trials in neurorehabilitation based upon experiences encountered by the EXCITE team. Cost factors and patient attributes, both of which profoundly influence the ability of clinical researchers to execute the ideal study, are among these factors. In particular, the costs associated with large trials necessitate compromise in study design or implementation, resulting in a dichotomy between what should be undertaken and what can be accomplished.

Differential patterns of cortical reorganization following constraint-induced movement therapy during early and late period after stroke: A preliminary study

OBJECTIVE Constraint-induced movement therapy (CIMT) has been shown to improve upper extremity voluntary movement and change cortical movement representation after stroke. Direct comparison of the differential degree of cortical reorganization according to chronicity in stroke subjects receiving CIMT has not been performed and was the purpose of this study. We hypothesized that a higher degree of cortical reorganization would occur in the early (less than 9 months post-stroke) compared to the late group (more than 12 months post-stroke). METHODS 17 early and 9 late subjects were enrolled. Each subject was evaluated using transcranial magnetic stimulation (TMS) and the Wolf Motor Function Test (WMFT) and received CIMT for 2 weeks. RESULTS The early group showed greater improvement in WMFT compared with the late group. TMS motor maps showed persistent enlargement in both groups but the late group trended toward more enlargement. The map shifted posteriorly in the late stroke group. The main limitation was the small number of TMS measures that could be acquired due to high motor thresholds, particularly in the late group. CONCLUSION CIMT appears to lead to greater improvement in motor function in the early phase after stroke. Greater cortical reorganization in map size and position occurred in the late group in comparison. SIGNIFICANCE The contrast between larger functional gains in the early group vs larger map changes in the late group may indicate that mechanisms of recovery change over the several months following stroke or that map changes are a time-dependent epiphenomenon.

Neural correlates supporting sensory discrimination after left hemisphere stroke.

BACKGROUND Nearly half of stroke patients have impaired sensory discrimination, however, the neural structures that support post-stroke sensory function have not been described. OBJECTIVES 1) To evaluate the role of the primary somatosensory (S1) cortex in post-stroke sensory discrimination and 2) To determine the relationship between post-stroke sensory discrimination and structural integrity of the sensory component of the superior thalamic radiation (sSTR). METHODS 10 healthy adults and 10 individuals with left hemisphere stroke participated. Stroke participants completed sensory discrimination testing. An fMRI was conducted during right, impaired hand sensory discrimination. Fractional anisotropy and volume of the sSTR were quantified using diffusion tensor tractography. RESULTS Sensory discrimination was impaired in 60% of participants with left stroke. Peak activation in the left (S1) did not correlate with sensory discrimination ability, rather a more distributed pattern of activation was evident in post-stroke subjects with a positive correlation between peak activation in the parietal cortex and discrimination ability (r=.70, p=.023). The only brain region in which stroke participants had significantly different cortical activation than control participants was the precuneus. Region of interest analysis of the precuneus across stroke participants revealed a positive correlation between peak activation and sensory discrimination ability (r=.77, p=.008). The L/R ratio of sSTR fractional anisotropy also correlated with right hand sensory discrimination (r=.69, p=.027). CONCLUSIONS Precuneus cortex, distributed parietal lobe activity, and microstructure of the sSTR support sensory discrimination after left hemisphere stroke.