Background. Improvement of postural control in persons with multiple sclerosis (PwMS) is an important target for neurorehabilitation. Although PwMS are able to improve postural performance with training, the neural underpinnings of these improvements are poorly understood. Objective. To understand the neural underpinnings of postural motor learning in PwMS. Methods. Supraspinal white matter structural connectivity in PwMS was correlated with improvements in postural performance (balancing on an oscillating surface over 25 trials) and retention of improvements (24 hours later). Results. Improvement in postural performance was directly correlated to microstructural integrity of white matter tracts, measured as radial diffusivity, in the corpus callosum, posterior parieto-sensorimotor fibers and the brainstem in PwMS. Within the corpus callosum, the genu and midbody (fibers connecting the prefrontal and primary motor cortices, respectively) were most strongly correlated to improvements in postural control. Twenty-four-hour retention was not correlated to radial diffusivity. Conclusion. PwMS who exhibited poorer white matter tract integrity connecting the cortical hemispheres via the corpus callosum showed the most difficulty learning to control balance on an unstable surface. Prediction of improvements in postural control through training (ie, motor learning) via structural imaging of the brain may allow for identification of individuals who are particularly well suited for postural rehabilitation interventions.
Background. Following biceps transfer to enable elbow extension in individuals with tetraplegia, motor re-education may be facilitated by greater corticomotor excitability. Arm posture modulates corticomotor excitability of the nonimpaired biceps. If arm posture also modulates excitability of the transferred biceps, posture may aid in motor re-education. Objective. Our objective was to determine whether multi-joint arm posture affects corticomotor excitability of the transferred biceps similar to the nonimpaired biceps. We also aimed to determine whether corticomotor excitability of the transferred biceps is related to elbow extension strength and muscle length. Methods. Corticomotor excitability was assessed in 7 arms of individuals with tetraplegia and biceps transfer using transcranial magnetic stimulation and compared to biceps excitability of nonimpaired individuals. Single-pulse transcranial magnetic stimulation was delivered to the motor cortex with the arm in functional postures at rest. Motor-evoked potential amplitude was recorded via surface electromyography. Elbow moment was recorded during maximum isometric extension trials, and muscle length was estimated using a biomechanical model. Results. Arm posture modulated corticomotor excitability of the transferred biceps differently than the nonimpaired biceps. Elbow extension strength was positively related and muscle length was unrelated, respectively, to motor-evoked potential amplitude across the arms with biceps transfer. Conclusions. Corticomotor excitability of the transferred biceps is modulated by arm posture and may contribute to strength outcomes after tendon transfer. Future work should determine whether modulating corticomotor excitability via posture promotes motor re-education during the rehabilitative period following surgery.
Background and objective. Proportional recovery of upper-extremity motor function and aphasia after stroke may suggest common mechanisms for spontaneous neurobiological recovery. This study aimed to investigate if the proportional recovery rule also applies to visuospatial neglect (VSN) in right-hemispheric first-ever ischemic stroke patients and explored the possible common underlying mechanisms. Methods. Patients with upper-limb paresis and VSN were included. Recovery defined as the change in Letter Cancellation Test (LCT) score at ~8 days and 6 months poststroke. Potential recovery defined as LCTmax-LCTinitial = 20 – LCTinitial. Hierarchical clustering separated fitters and nonfitters of the prediction rule. A cutoff value on LCTmax-LCTinitial was determined. The change in LCT and Fugl-Meyer Assessment Upper Extremity was expressed as a percentage of the total possible score to investigate the communality of proportional recovery. Results. Out of 90 patients, 80 displayed proportional recovery of VSN (ie, "fitters," 0.97; 95% CI = 0.82-1.12). All patients who did not follow the prediction rule for VSN (ie, "nonfitters") had ≥15 missing O’s at baseline and failed to show proportional recovery of the upper limb. Conclusions. This study shows that the proportional recovery rule also applies to patients with VSN poststroke. Patients who fail to show proportional recovery of VSN are the same patients who fail to show proportional recovery of the upper limb. These findings support the idea of common intrahemispheric mechanisms underlying spontaneous neurobiological recovery in the first months poststroke. Future studies should investigate the prognostic clinical and neurobiological markers of these subgroups.
Background. Acquired brain injury (ABI) can impair executive function, impeding planning and attainment of intentions. Research shows promise for some goal-management rehabilitation interventions. However, evidence that alerts assist monitoring and completion of day-to-day intentions is limited. Objective. To examine the efficacy of brief goal-directed rehabilitation paired with periodic SMS text messages designed to enhance executive monitoring of intentions (assisted intention monitoring [AIM]). Methods. A randomized, double-blind, controlled trial was conducted. Following a baseline phase, 74 people with ABI and executive problems were randomized to receive AIM or control (information and games) for 3 weeks (phase 1) before crossing over to either AIM or no intervention (phase 2). The primary outcome was change in composite score of proportion of daily intentions achieved. A total of 59 people (71% male; 46% traumatic brain injury) completed all study phases. Results. Per protocol crossover analysis found a significant benefit of AIM for all intentions [F(1, 56) = 4.28; P = .04; f = 0.28; 3.7% mean difference; 95% CI = 0.1%-7.4%] and all intentions excluding a proxy prospective memory task [F(1, 55) = 4.79; P = .033; f = 0.28, medium effect size; 3% mean difference; 95% CI = 0.3%-5.6%] in the absence of significant changes on tests of executive functioning. Intention-to-treat analyses, comparing AIM against control at the end of phase 1 revealed no statistically significant differences in the attainment of intentions. Conclusion. Combining brief executive rehabilitation with alerts may be effective for some in improving achievement of daily intentions, but further evaluation of clinical effectiveness and mechanisms is required.
Most persons living with a spinal cord injury experience neuropathic pain in the months following their lesion, at the moment where they receive intensive gait rehabilitation. Based on studies using animal models, it has been proposed that central sensitization in nociceptive pathways (maladaptive plasticity) and plasticity related to motor learning (adaptive plasticity) share common neural mechanisms and compete with each other. This article aims to address the discrepancy between the growing body of basic science literature supporting this hypothesis and the general belief in rehabilitation research that pain and gait rehabilitation represent two independent problems. First, the main findings from basic research showing interactions between nociception and learning in the spinal cord will be summarized, focusing both on evidence demonstrating the impact of nociception on motor learning and of motor learning on central sensitization. Then, the generalizability of these findings in animal models to humans will be discussed. Finally, the way potential interactions between nociception and motor learning are currently taken into account in clinical research in patients with spinal cord injury will be presented. To conclude, recommendations will be proposed to better integrate findings from basic research into future clinical research in persons with spinal cord injury.
Background. A common assumption is that changes in upper limb (UL) capacity, or what an individual is capable of doing, translates to improved UL performance in daily life, or what an individual actually does. This assumption should be explicitly tested for individuals with UL paresis poststroke. Objective. To examine changes in UL performance after an intensive, individualized, progressive, task-specific UL intervention for individuals at least 6 months poststroke. Methods. Secondary analysis on 78 individuals with UL paresis who participated in a phase II, single-blind, randomized parallel dose-response trial. Participants were enrolled in a task-specific intervention for 8 weeks. Participants were randomized into 1 of 4 treatment groups with each group completing different amounts of UL movement practice. UL performance was assessed with bilateral, wrist-worn accelerometers once a week for 24 hours throughout the duration of the study. The 6 accelerometer variables were tested for change and the influence of potential modifiers using hierarchical linear modeling. Results. No changes in UL performance were found on any of the 6 accelerometer variables used to quantify UL performance. Neither changes in UL capacity nor the overall amount of movement practice influenced changes in UL performance. Stroke chronicity, baseline UL capacity, concordance, and ADL status significantly increased the baseline starting points but did not influence the rate of change (slopes) for participants. Conclusions. Improved motor capacity resulting from an intensive outpatient UL intervention does not appear to translate to increased UL performance outside the clinic.
Background. Mirror therapy provides a visual illusion of a normal moving limb by using the mirror reflection of the unaffected arm instead of viewing the paretic limb and is used in rehabilitation to improve hand function. Little is known about the mechanism underlying its effect in children with hemiparesis. Objective. To investigate the effect of the mirror illusion (MI) on the excitability of the primary motor cortex (M1) in children and adolescents. Methods. Twelve patients with hemiparesis (10-20 years) and 8 typically developing subjects (8-17 years) participated. Corticospinal reorganization was classified as contralateral (projection from contralateral hemisphere to affected hand) or ipsilateral (projection from ipsilateral hemisphere to affected hand). M1 excitability of the hemisphere projecting to the affected (nondominant in typically developing subjects) hand was obtained during 2 different conditions using single-pulse transcranial magnetic stimulation (TMS). Each condition (without/with mirror) consisted of a unimanual and a bimanual task. Motor-evoked potentials (MEPs) were recorded from the abductor pollicis brevis and flexor digitorum superficialis muscles. Results. MEP amplitudes were significantly increased during the mirror condition (P = .005) in typically developing subjects and in patients with contralateral reorganization. No significant effect of MI was found in subjects with ipsilateral reorganization. MI increased M1 excitability during active movements only. This increase was not correlated to hand function. Conclusion. MI increases the excitability of M1 in hemiparetic patients with contralateral corticospinal organization and in typically developing subjects. This finding provides neurophysiological evidence supporting the application of mirror therapy in selected children and adolescents with hemiparesis.
Background. The Arm Motor Ability Test (AMAT) is used to assess and quantify upper-extremity (UE) functional limitation in stroke and other conditions. However, the AMAT score change indicative of important and clinically meaningful change has not been determined. Objective. To determine the clinically important difference (CID) for the AMAT for individuals with stroke exhibiting mild to moderate hemiparesis. Methods. A total of 146 chronic stroke survivors exhibiting stable, mild to moderate UE hemiparesis were administered the AMAT before and after interventions targeting their affected UEs. Patients and treating therapists rated perceived amount of UE motor recovery for each participant on a global rating of change (GROC) scale evaluating several facets of UE movement (grasp, release, move the affected UE, perform 5 important functional tasks, overall UE function). Estimated CID of the Functional Ability Scale of the AMAT was calculated using the receiver operating characteristics curve with the GROC scale as the anchor. Distribution-based methods were also used to estimate the CID. Results. Mean baseline, postintervention, and change in AMAT values for all participants were 3.0 (0.68), 3.3 (0.73), and 0.33 (0.43) respectively. The CID was estimated as an improvement of 0.32 to 0.42 when anchored by the therapist’s perception of improvement and 0.29 to 0.40 when anchored by the patient’s perception of improvement. The CID using distribution-based methods ranged from 0.40 to 0.44. Conclusions. A change of 0.44 or greater on the AMAT indicates a clinically meaningful improvement in UE functional movements. Clinicians should use this value to determine goals and interpret change scores.
Background. Perinatal stroke causes most hemiparetic cerebral palsy. Ipsilateral connections from nonlesioned hemisphere to affected hand are common. The nonlesioned primary motor cortex (M1) determines function and is a potential therapeutic target but its neurophysiology is poorly understood. Objective. We aimed to characterize the neurophysiological properties of the nonlesioned M1 in children with perinatal stroke and their relationship to clinical function. Methods. Fifty-two participants with hemiparetic cerebral palsy and magnetic resonance imaging–confirmed perinatal stroke and 40 controls aged 8 to 18 years completed the same transcranial magnetic stimulation (TMS) protocol. Single-pulse TMS to nonlesioned M1 determined rest and active motor thresholds (RMT/AMT), motor-evoked potential (MEP) latencies, and stimulus recruitment curves (SRC: 100%-150% RMT). Paired-pulse TMS evaluated short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF). Ipsilateral (IP) participants (ipsilateral MEP ≥0.05 mV in ≥5/20 trials) were compared with contralateral MEP only, nonipsilateral (NI) participants. Assisting Hand and Melbourne assessments quantified clinical function. Results. Twenty-five IP were compared with 13 NI (n = 38, median age 12 years, 66% male). IP had lower motor function. SRC to unaffected hand were comparable between IP and NI while IP had smaller ipsilateral SRC. Ipsilateral MEP latencies were prolonged (23.5 ± 1.8 vs 22.2 ± 1.5 ms contra, P < .001). Contralateral SICI was different between IP (–42%) and NI (–20%). Ipsilateral SICI was reduced (–20%). Contralateral ICF was comparable between groups (+43%) and ipsilaterally (+43%). Measures correlated between contralateral and ipsilateral sides. Conclusion. Neurophysiology of nonlesioned M1 and its relationship to motor function is measureable in children with perinatal stroke. Correlation of excitability and intracortical circuitry measures between contralateral and ipsilateral sides suggests common control mechanisms.
Although motor learning theory has led to evidence-based practices, few trials have revealed the superiority of one theory-based therapy over another after stroke. Nor have improvements in skills been as clinically robust as one might hope. We review some possible explanations, then potential technology-enabled solutions. Over the Internet, the type, quantity, and quality of practice and exercise in the home and community can be monitored remotely and feedback provided to optimize training frequency, intensity, and progression at home. A theory-driven foundation of synergistic interventions for walking, reaching and grasping, strengthening, and fitness could be provided by a bundle of home-based Rehabilitation Internet-of-Things (RIoT) devices. A RIoT might include wearable, activity-recognition sensors and instrumented rehabilitation devices with radio transmission to a smartphone or tablet to continuously measure repetitions, speed, accuracy, forces, and temporal spatial features of movement. Using telerehabilitation resources, a therapist would interpret the data and provide behavioral training for self-management via goal setting and instruction to increase compliance and long-term carryover. On top of this user-friendly, safe, and conceptually sound foundation to support more opportunity for practice, experimental interventions could be tested or additions and replacements made, perhaps drawing from virtual reality and gaming programs or robots. RIoT devices continuously measure the actual amount of quality practice; improvements and plateaus over time in strength, fitness, and skills; and activity and participation in home and community settings. Investigators may gain more control over some of the confounders of their trials and patients will have access to inexpensive therapies.
Background. Reorganization of the corticospinal tract (CST) can occur in unilateral spastic cerebral palsy (USCP). The affected hand can be controlled via (1) typical contralateral projections from the lesioned hemisphere, (2) ipsilateral projections from the nonlesioned hemisphere, and (3) a combination of contralateral and ipsilateral projections (ie, bilateral). Intensive bimanual therapy and constraint-induced movement therapy (CIMT) improve hand function of children with USCP. Earlier it was suggested that the CST connectivity pattern may influence the efficacy of CIMT. Objective. To examine whether CST projection pattern influences the efficacy of intensive bimanual therapy in children with USCP. Participants. Thirty-three children with USCP (age 8.9 ± 2.6 years, 16 females). Methods. Bimanual therapy was provided in a day-camp setting (90 hours). Participants were involved in different bimanual play and functional activities actively engaging both hands. Hand function was tested before and after the intervention with the Jebsen-Taylor Test of Hand Function, Assisting Hand Assessment, ABILHAND-Kids, and the Canadian Occupational Performance Measure. Single-pulse transcranial magnetic stimulation (TMS) was used to determine each child’s CST projection pattern (ie, ipsilateral, contralateral, or bilateral). Results. Children whose affected hand was controlled only by ipsilateral CST projections had worse Jebsen-Taylor Test of Hand Function and Assisting Hand Assessment scores than children in the contralateral group at baseline. Bimanual hand use and functional hand use was independent of CST projection pattern. After bimanual therapy, improvements on all outcome measures were observed, and these improvements were independent of the CST connectivity pattern. Conclusion. The efficacy of bimanual therapy on hand function in children with USCP appears to be independent of CST connectivity pattern.
Background. Trunk function is important for standing balance, mobility, and functional outcome after stroke, but few studies have evaluated the effects of exercises aimed at improving core stability in stroke patients. Objective. To investigate the effectiveness of core stability training on trunk function, standing balance, and mobility in stroke patients. Methods. An assessor-blinded, randomized controlled trial was undertaken in a stroke rehabilitation ward, with 32 participants randomly assigned to an experimental group or a control group (n = 16 each). The experimental group received 400 minutes of core stability training in place of conventional programs within total training time, while the control group received only conventional programs. Primary outcome measures were evaluated using the Trunk Impairment Scale (TIS), which reflects trunk function. Secondary outcome measures were evaluated by pelvic tilt active range of motion in the sagittal plane, the Balance Evaluation Systems Test–brief version (Brief-BESTest), Functional Reach test, Timed Up-and-Go test (TUG), and Functional Ambulation Categories (FAC). A general linear repeated-measures model was used to analyze the results. Results. A treatment effect was found for the experimental group on the dynamic balance subscale and total score of the TIS (P = .002 and P < .001, respectively), pelvic tilt active range of motion (P < .001), Brief-BESTest (P < .001), TUG (P = .008), and FAC (P = .022). Conclusions. Core stability training has beneficial effects on trunk function, standing balance, and mobility in stroke patients. Our findings might provide support for introducing core stability training in stroke rehabilitation.
Background. Traumatic brain injury (TBI) has been associated with impairments in inhibiting prepotent motor responses triggered by infrequent external signals (ie, reactive inhibition). It is unclear whether proactive preparation to inhibit upcoming responses is also affected (ie, proactive inhibition). Successful inhibition relies on frontosubcortical interactions; therefore, impairments might be linked with gray matter atrophy in subcortical structures. Objective. We investigated reactive and proactive inhibition in TBI and control groups, and their relationship with subcortical gray matter. Methods. Participants performed a response inhibition task in which the probability of stopping was manipulated. Reactive inhibition was measured as the stop-signal reaction time (SSRT) when the probability of stopping was low. Proactive inhibition was measured as the change in SSRT and in go response time with increasing probability of stopping. Subcortical gray matter structures were automatically segmented with FSL-FIRST. Group differences in subregional volume and associations with reactive and proactive inhibition efficiency were investigated using shape analysis. Results. Reactive inhibition was impaired in TBI, as indicated by longer SSRTs. Moreover, the degree of atrophy in subregions of subcortical structures was predictive for SSRT in TBI. In contrast, proactive inhibition was not affected because both groups showed no response time slowing as a function of stopping probability. Proactive inhibition efficiency could be predicted by local volume in the anterior left putamen, bilateral pallidum, and right thalamus in controls but not in TBI. Conclusions. Our results reveal that proactive inhibition seems unaffected in TBI and that volume of subregions of subcortical nuclei is predictive for response inhibition proficiency and of clinical relevance in TBI.
Background and Objective: Stroke rehabilitation assumes motor learning contributes to motor recovery, yet motor learning in stroke has received little systematic investigation. Here we aimed to illustrate that despite matching levels of performance on a task, a trained patient should not be considered equal to an untrained patient with less impairment. Methods: We examined motor learning in healthy control participants and groups of stroke survivors with mild-to-moderate or moderate-to-severe motor impairment. Participants performed a series of isometric contractions of the elbow flexors to navigate an on-screen cursor to different targets, and trained to perform this task over a 4-day period. The speed-accuracy trade-off function (SAF) was assessed for each group, controlling for differences in self-selected movement speeds between individuals. Results: The initial SAF for each group was proportional to their impairment. All groups were able to improve their performance through skill acquisition. Interestingly, training led the moderate-to-severe group to match the untrained (baseline) performance of the mild-to-moderate group, while the trained mild-to-moderate group matched the untrained (baseline) performance of the controls. Critically, this did not make the two groups equivalent; they differed in their capacity to improve beyond this matched performance level. Specifically, the trained groups had reached a plateau, while the untrained groups had not. Conclusions: Despite matching levels of performance on a task, a trained patient is not equal to an untrained patient with less impairment. This has important implications for decisions both on the focus of rehabilitation efforts for chronic stroke, as well as for returning to work and other activities.
Objective. Structural connectivity analysis based on graph theory and diffusion tensor imaging tractography is a novel method that quantifies the topological characteristics in the brain network. This study aimed to examine structural connectivity changes following the Attention Intervention and Management (AIM) program designed to improve attention and executive function (EF) in children with traumatic brain injury (TBI). Methods. Seventeen children with complicated mild to severe TBI (13.66 ± 2.68 years; >12 months postinjury) completed magnetic resonance imaging (MRI) and neurobehavioral measures at time 1, 10 of whom completed AIM and assessment at time 2. Eleven matched healthy comparison (HC) children (13.37 ± 2.08 years) completed MRI and neurobehavioral assessment at both time points, but did not complete AIM. Network characteristics were analyzed to quantify the structural connectivity before and after the intervention. Results. Mixed model analyses showed that small-worldness was significantly higher in the TBI group than the HC group at time 1, and both small-worldness and normalized clustering coefficient decreased significantly at time 2 in the TBI group whereas the HC group remained relatively unchanged. Reductions in mean local efficiency were significantly correlated with improvements in verbal inhibition and both parent- and child-reported EF. Increased normalized characteristic path length was significantly correlated with improved sustained attention. Conclusion. The results provide preliminary evidence suggesting that graph theoretical analysis may be a sensitive tool in pediatric TBI for detecting (a) abnormalities of structural connectivity in brain network and (b) structural neuroplasticity associated with neurobehavioral improvement following a short-term intervention for attention and EF.
Stroke survivors often have a slow, asymmetric walking pattern. They also walk with a higher metabolic cost than healthy, age-matched controls. It is often assumed that spatial-temporal asymmetries contribute to the increased metabolic cost of walking poststroke. However, elucidating this relationship is made challenging because of the interdependence between spatial-temporal asymmetries, walking speed, and metabolic cost. Here, we address these potential confounds by measuring speed-dependent changes in metabolic cost and implementing a recently developed approach to dissociate spatial versus temporal contributions to asymmetry in a sample of stroke survivors. We used expired gas analysis to compute the metabolic cost of transport (CoT) for each participant at 4 different walking speeds: self-selected speed, 80% and 120% of their self-selected speed, and their fastest comfortable speed. We also computed CoT for a sample of age- and gender-matched control participants who walked at the same speeds as their matched stroke survivor. Kinematic data were used to compute the magnitude of a number of variables characterizing spatial-temporal asymmetries. Across all speeds, stroke survivors had a higher CoT than controls. We also found that our sample of stroke survivors did not choose a self-selected speed that minimized CoT, contrary to typical observations in healthy controls. Multiple regression analyses revealed negative associations between speed and CoT and a positive association between asymmetries in foot placement relative to the trunk and CoT. These findings suggest that interventions designed to increase self-selected walking speed and reduce foot-placement asymmetries may be ideal for improving walking economy poststroke.
Background. Attention is frequently impaired after stroke, and its impairment is associated with poor quality of life. Physical activity benefits attention in healthy populations and has also been associated with recovery after brain injury. Objective. We investigated the relationship between objectively measured daily physical activity, attention network connectivity, and attention task performance after stroke. We hypothesized that increased daily physical activity would be associated with improved attention network function. Methods. Stroke patients (n = 62; mean age = 67 years, SD = 12.6 years) and healthy controls (n = 27; mean age = 68 years, SD = 6 years) underwent cognitive testing and 7 minutes of functional magnetic resonance imaging in the resting-state. Patients were tested 3 months after ischemic stroke. Physical activity was monitored with an electronic armband worn for 7 days. Dorsal and ventral attention network function was examined using seed-based connectivity analyses. Results. Greater daily physical activity was associated with increased interhemispheric connectivity of the superior parietal lobule in the dorsal attention network (DAN; P < .05, false discovery rate corrected). This relationship was not explained by stroke lesion volume. Importantly, stronger connectivity in this region was related to faster reaction time in 3 attention tasks, as revealed by robust linear regression. The relationship remained after adjusting for age, gray matter volume, and white matter hyperintensity load. Conclusions. Daily physical activity was associated with increased resting interhemispheric connectivity of the DAN. Increased connectivity was associated with faster attention performance, suggesting a cognitive correlate to increased network connectivity. Attentional modulation by physical activity represents a key focus for intervention studies.
Background. The use of exercise in amyotrophic lateral sclerosis (ALS) is controversial. Although moderate exercise appears to be beneficial for limb muscles in ALS, the effects of exercise on bulbar muscles such as the tongue have not been studied. Objective. To determine the effects of tongue force training on bulbar motor function in the SOD1-G93A rat model of ALS. Methods. We compared the effects of tongue force training on bulbar motor function and neuromuscular junction innervation in female SOD1-G93A rats and age-matched female wild-type controls. Half of each group underwent afternoon tongue force training sessions, and all rats were tested under minimal force conditions in the mornings. Results. Tongue force did not differ between the SOD1-G93A rats and healthy controls during the morning testing sessions, nor was it affected by training. Surprisingly, decreases in tongue motility, the number of licks per session, and body weight were greater in the tongue force–trained SOD1-G93A rats. Forelimb grip force, survival, and denervation of the genioglossus (GG) muscle did not differ between the trained and untrained SOD1-G93A rats. GG innervation was correlated with changes in tongue force but not tongue motility in SOD1-G93A rats at end stage. Conclusions. The results indicate a potential deleterious effect of tongue force training on tongue motility in female SOD1-G93A rats. The lack of a relationship between GG innervation and tongue motility suggests that factors other than lower–motor neuron integrity likely accounted for this effect.
Background. Upper limb (UL) poststroke hemiparesis commonly leads to chronic disability. Despite moderate-to-good clinical recovery, many patients with UL hemiparesis still do not fully use their arm in daily tasks. Decreased arm use may be related to deficits in performance of more complex movement than what is usually assessed clinically. Objective. To identify differences between poststroke and nondisabled control subjects in making complex corrective movements to avoid an obstacle in the reaching path. Methods. Subjects rapidly reached for a juice bottle on a refrigerator shelf with their hemiparetic or dominant (controls) arm viewed in a large-screen projected 3D virtual environment. In random trials, a sliding door partially obstructed the reaching path. A successful trial was one in which subjects touched the bottle without their arm or hand hitting the door. Results. Fewer participants with stroke (12%) were successful at a 65% success rate in avoiding the door compared to controls (42%). Subjects with stroke also initiated corrections later (further) in the reaching path (100.7 ± 77.6 mm) compared to controls (51.6 ± 31.0 mm) resulting in a reduced margin of error. While both groups used similar endpoint movement strategies for obstructed reaching, subjects with stroke used less elbow and more trunk movement. Participants who reported being more confident using their hemiparetic arm had higher success rates. Conclusion. Arm movement deficits can be identified when complex tasks are evaluated. Deficits in higher-order motor function such as obstacle avoidance behavior may decrease actual arm use in individuals with mild-to-moderate hemiparesis and should be evaluated in routine clinical practice.
Background. Rodents are the primary animal model of corticospinal injury and repair, yet current behavioral tests do not show the large deficits after injury observed in humans. Forearm supination is critical for hand function and is highly impaired by corticospinal injury in both humans and rats. Current tests of rodent forelimb function do not measure this movement. Objective. To determine if quantification of forelimb supination in rats reveals large-scale functional loss and partial recovery after corticospinal injury. Methods. We developed a knob supination device that quantifies supination using automated and objective methods. Rats in a reaching box have to grasp and turn a knob in supination in order to receive a food reward. Performance on this task and the single pellet reaching task were measured before and after 2 manipulations of the pyramidal tract: a cut lesion of 1 pyramid and inactivation of motor cortex using 2 different drug doses. Results. A cut lesion of the corticospinal tract produced a large deficit in supination. In contrast, there was no change in pellet retrieval success. Supination function recovered partially over 6 weeks after injury, and a large deficit remained. Motor cortex inactivation produced a dose-dependent loss of knob supination; the effect on pellet reaching was more subtle. Conclusions. The knob supination task reveals in rodents 3 signature hand function changes observed in humans with corticospinal injury: (1) large-scale loss with injury, (2) partial recovery in the weeks after injury, and (3) loss proportional to degree of dysfunction.
Background. After cerebral ischemia, disruption and subsequent reorganization of functional connections occur both locally and remote to the lesion. Recently, complexity of brain connectivity has been described using graph theory, a mathematical approach that depicts important properties of complex systems by quantifying topologies of network representations. Functional and dynamic changes of brain connectivity can be reliably analyzed via electroencephalography (EEG) recordings even when they are not yet reflected in structural changes of connections. Objective. We tested whether and how ischemic stroke in the acute stage may determine changes in small-worldness of cortical networks as measured by cortical sources of EEG. Methods. Graph characteristics of EEG of 30 consecutive stroke patients in acute stage (no more than 5 days after the event) were examined. Connectivity analysis was performed using eLORETA in both hemispheres. Results. Network rearrangements were mainly detected in delta, theta, and alpha bands when patients were compared with healthy subjects. In delta and alpha bands similar findings were observed in both hemispheres regardless of the side of ischemic lesion: bilaterally decreased small-worldness in the delta band and bilaterally increased small-worldness in the alpha2 band. In the theta band, bilaterally decreased small-worldness was observed only in patients with stroke in the left hemisphere. Conclusions. After an acute stroke, brain cortex rearranges its network connections diffusely, in a frequency-dependent modality probably in order to face the new anatomical and functional frame.
Background. Conventionally, change in motor performance is quantified with discrete measures of behavior taken pre- and postpractice. As a high degree of movement variability exists in motor performance after stroke, pre- and posttesting of motor skill may lack sensitivity to predict potential for motor recovery. Objective. Evaluate the use of predictive models of motor learning based on individual performance curves and clinical characteristics of motor function in individuals with stroke. Methods. Ten healthy and fourteen individuals with chronic stroke performed a continuous joystick-based tracking task over 6 days, and at a 24-hour delayed retention test, to assess implicit motor sequence learning. Results. Individuals with chronic stroke demonstrated significantly slower rates of improvements in implicit sequence-specific motor performance compared with a healthy control (HC) group when root mean squared error performance data were fit to an exponential function. The HC group showed a positive relationship between a faster rate of change in implicit sequence-specific motor performance during practice and superior performance at the delayed retention test. The same relationship was shown for individuals with stroke only after accounting for overall motor function by including Wolf Motor Function Test rate in our model. Conclusion. Nonlinear information extracted from multiple time points across practice, specifically the rate of motor skill acquisition during practice, relates strongly with changes in motor behavior at the retention test following practice and could be used to predict optimal doses of practice on an individual basis.
Background. Constraint-induced aphasia therapy (CIAT) has proven effective in patients with subacute and chronic forms of aphasia. It has remained unclear, however, whether intensity of therapy or constraint is the relevant factor. Data about intensive speech and language therapy (SLT) are conflicting. Objective. To identify the effective component of CIAT and assess the feasibility of SLT in the acute stage after stroke. Method. A total of 60 patients with aphasia (68.2 ± 11.7 years) were enrolled 18.9 days after first-ever stroke. They were randomly distributed into 3 groups: (1) CIAT group receiving therapy for 3 hours per day (10 workdays, total 30 hours); (2) conventional communication treatment group, with same intensity without constraints; and (3) control group receiving individual therapy twice a day as well as group therapy (total 14 hours). Patients were assessed pretreatment and posttreatment using the Aachener Aphasia Test (primary end point: token test) and the Communicative Activity Log (CAL). Results. Pretreatment, there were no between-group differences. Posttreatment, all groups showed significant improvements without between-group differences. Conclusion. It was found that 14 hours of aphasia therapy administered within 2 weeks as individual therapy, focusing on individual deficits, combined with group sessions has proven to be most efficient. This approach yielded the same outcome as 30 hours of group therapy, either in the form of CIAT or group therapy without constraints. SLT in an intensive treatment schedule is feasible and was well tolerated in the acute stage after stroke.
Background. Insulin-like growth factor-1 (IGF-1) is neuroprotective after stroke and is regulated by insulin-like binding protein-3 (IGFBP-3). In healthy individuals, exercise and improved aerobic fitness (peak oxygen uptake; peak VO2) increases IGF-1 in circulation. Understanding the relationship between estimated prestroke aerobic fitness and IGF-1 and IGFBP-3 after stroke may provide insight into the benefits of exercise and aerobic fitness on stroke recovery. Objective. The purpose of this study was to determine the relationship of IGF-1 and IGFBP-3 to estimated prestroke peak VO2 in individuals with acute stroke. We hypothesized that (1) estimated prestroke peak VO2 would be related to IGF-1 and IGFBP-3 and (2) individuals with higher than median IGF-1 levels will have higher estimated prestroke peak VO2 compared to those with lower than median levels. Methods. Fifteen individuals with acute stroke had blood sampled within 72 hours of hospital admission. Prestroke peak VO2 was estimated using a nonexercise prediction equation. IGF-1 and IGFBP-3 levels were quantified using enzyme-linked immunoassay. Results. Estimated prestroke peak VO2 was significantly related to circulating IGF-1 levels (r = .60; P = .02) but not IGFBP-3. Individuals with higher than median IGF-1 (117.9 ng/mL) had significantly better estimated aerobic fitness (32.4 ± 6.9 mL kg–1 min–1) than those with lower than median IGF-1 (20.7 ± 7.8 mL kg–1 min–1; P = .03). Conclusions. Improving aerobic fitness prior to stroke may be beneficial by increasing baseline IGF-1 levels. These results set the groundwork for future clinical trials to determine whether high IGF-1 and aerobic fitness are beneficial to stroke recovery by providing neuroprotection and improving function.
People with multiple sclerosis (MS) frequently complain of excessive fatigue, which is the most disabling symptom for half of them. While the few drugs used to treat MS fatigue are of limited utility, we recently observed the efficacy of a personalized neuromodulation treatment. Here, we aim at strengthening knowledge of the brain network changes that occur when MS fatigue increases, using graph theory. We collected electroencephalographic (EEG; 23 or 64 channels) data in resting state with eyes open in 27 relapsing-remitting (RR) patients with mild MS (EDSS ≤2), suffering a wide range of fatigue as scored by the modified Fatigue Impact Scale (mFIS) (2-69, within a total range 0-84). To estimate graph theory small-world index (SW), we calculated the lagged linear coherence between EEG cortical eLORETA sources, in the standard frequency bands delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), beta2 (20-30 Hz), and gamma (30-45 Hz). We calculated the SW of these undirected and weighted networks separately in the four left and right frontal (motor) and parieto-occipito-temporal (sensory) brain networks. A correlative analysis demonstrated increased fatigue symptoms along with the SW specifically in the Sensory network of the left dominant hemisphere in the beta1 band (Pearson’s r = 0.404, P = .020). Our study indicates a specific involvement of the dominant-hemisphere sensory network in MS fatigue. It suggests that compensatory neuromodulation interventions could enhance efficacy in relieving this debilitating symptom by targeting this area.
Background. Ten percent of stroke survivors develop dementia, which increases to more than a third after recurrent stroke. Other survivors develop less severe vascular cognitive impairment. In the general population, depression, and diabetes interact in predicting dementia risk, and they are both prevalent in stroke. Objective. To assess the cumulative association of comorbid depressive symptoms and type 2 diabetes with cognitive outcomes among stroke survivors. Methods. Multicenter observational cohort study of people within 6 months of stroke. Depression and cognitive status were screened using the Center for Epidemiological Studies Depression (CES-D) scale and the Montreal Cognitive Assessment (MoCA), respectively. Processing speed, executive function and memory were assessed using the Trail Making Test parts A and B, and the 5 Word Delayed Free Recall task. Results. Among 342 participants (age 67.0 ± 13.5 years, 43.3% female, 46 ± 35 days poststroke), the prevalence of type 2 diabetes was 32.2% and depressive symptoms (CES-D ≥16) were found in 40.6%. Diabetes and depressive symptoms increased the risk of severe cognitive impairment (MoCA <20) with adjusted odds ratio (OR) 2.12 (95% confidence interval [CI] 1.20-3.74, P = .010) for 1 comorbidity and OR 3.18 (95% CI 1.26-8.02, P = .014) for both comorbidities. Associated cognitive deficits included executive function (F1, 168 = 3.43, P = .035) but not processing speed (F1, 168 = 1.86, P = .16) or memory (F1, 168 = 0.82, P = .44). Conclusions. Diabetes and depressive symptoms were associated cumulatively with poorer cognitive screening outcomes poststroke, particularly deficits in executive function. Having 1 comorbidity doubled the odds of screening for severe cognitive impairment, having both tripled the odds.
Background. The trunk plays a critical role in attenuating movement-related forces that threaten to challenge the body’s postural control system. For people with Parkinson’s disease (PD), disease progression often leads to dopamine-resistant axial symptoms, which impair trunk control and increase falls risk. Objective. This prospective study aimed to evaluate the relationship between impaired trunk muscle function, segmental coordination, and future falls in people with PD. Methods. Seventy-nine PD patients and 82 age-matched controls completed clinical assessments and questionnaires to establish their medical history, symptom severity, balance confidence, and falls history. Gait characteristics and trunk muscle activity were assessed using 3-dimensional motion analysis and surface electromyography. The incidence, cause, and consequence of any falls experienced over the next 12 months were recorded and indicated that 48 PD and 29 control participants fell at least once during this time. Results. PD fallers had greater peak and baseline lumbar multifidus (LMF) and thoracic erector spinae (TES) activations than control fallers and nonfallers. Analysis of covariance indicated that the higher LMF activity was attributable to the stooped posture adopted by PD fallers, but TES activity was independent of medication use, symptom severity, and trunk orientation. Furthermore, greater LMF and TES baseline activity contributed to increasing lateral head, trunk, and pelvis movements in PD fallers but not nonfallers or controls. Conclusions. The results provide evidence of neuromuscular deficits for PD fallers that are independent of medications, symptom severity, and posture and contribute to impaired head, trunk, and pelvis control associated with falls in this population.
Background. The brain may reorganize to optimize stroke recovery. Yet relatively little is known about neural correlates of training-facilitated recovery, particularly after loss of body sensations. Objective. Our aim was to characterize changes in brain activation following clinically effective touch discrimination training in stroke patients with somatosensory loss after lesions of primary/secondary somatosensory cortices or thalamic/capsular somatosensory regions using functional magnetic resonance imaging (fMRI). Methods. Eleven stroke patients with somatosensory loss, 7 with lesions involving primary (S1) and/or secondary (S2) somatosensory cortex (4 male, 58.7 ± 13.3 years) and 4 with lesions primarily involving somatosensory thalamus and/or capsular/white matter regions (2 male, 58 ± 8.6 years) were studied. Clinical and MRI testing occurred at 6 months poststroke (preintervention), and following 15 sessions of clinically effective touch discrimination training (postintervention). Results. Improved touch discrimination of a magnitude similar to previous clinical studies and approaching normal range was found. Patients with thalamic/capsular somatosensory lesions activated preintervention in left ipsilesional supramarginal gyrus, and postintervention in ipsilesional insula and supramarginal gyrus. In contrast, those with S1/S2 lesions did not show common activation preintervention, only deactivation in contralesional superior parietal lobe, including S1, and cingulate cortex postintervention. The S1/S2 group did, however, show significant change over time involving ipsilesional precuneus. This change was greater than for the thalamic/capsular group (P = .012; d = –2.43; CI = –0.67 to –3.76). Conclusion. Different patterns of change in activation are evident following touch discrimination training with thalamic/capsular lesions compared with S1/S2 cortical somatosensory lesions, despite common training and similar improvement.
Background and purpose. This study compared the effect of cyclic neuromuscular electrical stimulation (NMES), electromyographically (EMG)-triggered NMES, and sensory stimulation on motor impairment and activity limitations in patients with upper-limb hemiplegia. Methods. This was a multicenter, single-blind, multiarm parallel-group study of nonhospitalized hemiplegic stroke survivors within 6 months of stroke. A total of 122 individuals were randomized to receive either cyclic NMES, EMG-triggered NMES, or sensory stimulation twice every weekday in 40-minute sessions, over an 8 week-period. Patients were followed for 6 months after treatment concluded. Results. There were significant increases in the Fugl-Meyer Assessment [F(1, 111) = 92.6, P < .001], FMA Wrist and Hand [F(1, 111) = 66.7, P < .001], and modified Arm Motor Ability Test [mAMAT; time effect: F(1, 111) = 91.0, P < .001] for all 3 groups. There was no significant difference in the improvement among groups in the FMA [F(2, 384) = 0.2, P = .83], FMA Wrist and Hand [F(2, 384) = 0.4, P = .70], or the mAMAT [F(2, 379) = 1.2, P = .31]. Conclusions. All groups exhibited significant improvement of impairment and functional limitation with electrical stimulation therapy applied within 6 months of stroke. Improvements were likely a result of spontaneous recovery. There was no difference based on the type of electrical stimulation that was administered.
Background. Antipsychotic drugs (APDs) are used to manage traumatic brain injury (TBI)–induced behavioral disturbances, such as agitation and aggression. However, APDs exhibiting D2 receptor antagonism impede cognitive recovery after experimental TBI. Hence, empirical evaluation of APDs with different mechanistic actions is warranted. Aripiprazole (ARIP) is a D2 and 5-hydroxytryptamine1A (5-HT1A) receptor agonist; pharmacotherapies with these properties enhance cognition after TBI. Objective. To test the hypothesis that ARIP would increase behavioral performance and decrease histopathology after TBI. Methods. Adult male rats were subjected to either a controlled cortical impact (CCI) or sham injury and then randomly assigned to ARIP (0.1 or 1.0 mg/kg) or VEH (1.0 mL/kg, saline vehicle) groups. Treatments began 24 hours after surgery and were administered once daily for 19 days. Motor (beam-balance/beam-walk) and cognitive (Morris water maze) performance was assessed on postoperative days 1 to 5 and 14 to 19, respectively, followed by quantification of hippocampal CA1,3 neuron survival and cortical lesion volume. Results. Beam-balance was significantly improved in the CCI + ARIP (1.0 mg/kg) group versus CCI + ARIP (0.1 mg/kg) and CCI + VEH (P < .05). Spatial learning and memory retention were significantly improved in the CCI + ARIP (0.1 mg/kg) group versus the CCI + ARIP (1.0 mg/kg) and CCI + VEH groups (P < .05). Both doses of ARIP reduced lesion size and CA3 cell loss versus VEH (P < .05). Importantly, neither dose of ARIP impeded functional recovery as previously reported with other APDs. Conclusion. These findings support the hypothesis and endorse ARIP as a safer APD for alleviating behavioral disturbances after TBI.
Background. Gait is influenced by higher order cognitive and cortical control mechanisms. Functional near infrared spectroscopy (fNIRS) has been used to examine frontal activation during walking in healthy older adults, reporting increased oxygenated hemoglobin (HbO2) levels during dual task walking (DT), compared with usual walking. Objective. To investigate the role of the frontal lobe during DT and obstacle negotiation, in healthy older adults and patients with Parkinson’s disease (PD). Methods. Thirty-eight healthy older adults (mean age 70.4 ± 0.9 years) and 68 patients with PD (mean age 71.7 ± 1.1 years,) performed 3 walking tasks: (a) usual walking, (b) DT walking, and (c) obstacles negotiation, with fNIRS and accelerometers. Linear-mix models were used to detect changes between groups and within tasks. Results. Patients with PD had higher activation during usual walking (P < .030). During DT, HbO2 increased only in healthy older adults (P < .001). During obstacle negotiation, HbO2 increased in patients with PD (P = .001) and tended to increase in healthy older adults (P = .053). Higher DT and obstacle cost (P < .003) and worse cognitive performance were observed in patients with PD (P = .001). Conclusions. A different pattern of frontal activation during walking was observed between groups. The higher activation during usual walking in patients with PD suggests that the prefrontal cortex plays an important role already during simple walking. However, higher activation relative to baseline during obstacle negotiation and not during DT in the patients with PD demonstrates that prefrontal activation depends on the nature of the task. These findings may have important implications for rehabilitation of gait in patients with PD.
Background: Sleep-wake disturbances are highly prevalent following traumatic brain injury (TBI), impeding rehabilitaion and quality of life. However, the mechanisms underlying these sleep disturnbances are unclear, and efficacious treatments are lacking. To investigate possible mechanisms underlying sleep disturbance in TBI, we examined characteristics of the circadian rhythm of melatonin, a hormone involved in sleep-wake regulation. We compared TBI patients reporting sleep disturbance with age- and gender-matched healthy volunteers. Methods: We conducted an overnight observational study with salivary melatonin samples collected hourly in 9 patients with severe TBI and 9 controls. Salivary dim light melatonin onset (DLMO) as well as melatonin synthesis onset (SynOn) and offset (SynOff) were used to determine circadian timing. Total overnight salivary melatonin production was calculated as the area under the curve from melatonin synthesis onset to offset. Results: Compared with healthy individuals, TBI patients showed 42% less melatonin production overnight (d = 0.87; P = .034). The timing of DLMO was delayed by approximately 1.5 hours in patients with TBI compared with controls (d = 1.23; P = .003). Conclusions: In patients with TBI, melatonin production was attenuated overnight, and the timing of melatonin secretion was delayed. We suggest that disruption to the circadian regulation of melatonin synthesis is a feature of severe TBI, possibly contributing to the sleep difficulties that are commonly reported in this population.
Background. Subcortical capsular stroke has a poor prognosis, and it is not yet fully understood how and under what circumstances reach training contributes to motor recovery. Objective. This study was performed to investigate changes in neuronal circuits and motor recovery in a chronic capsular stroke model in the presence or absence of reach training. Method. We generated photothrombotic capsular lesions in 42 Sprague-Dawley rats and evaluated motor recovery with or without daily training in a single-pellet reaching task (SPRT). We used 2-deoxy-2-[18F]-fluoro-D-glucose-microPET (positron emission tomography) to assess remodeling of neuronal circuits. Results. SPRT training was selectively beneficial only for the group with incomplete capsular destruction (P < .05), suggesting the relevance of plasticity in the remaining capsular fibers for motor recovery. Groups that did not receive SPRT training showed no motor recovery at all. The microPET analysis demonstrated that motor recovery was correlated with a reduction in cortical diaschisis in ipsilesional motor and sensory cortices and in the contralesional sensory cortex (Pearson’s correlation, P < .05). We also observed training-dependent subcortical activation in the contralesional red nucleus, the internal capsule, and the ventral hippocampus (P < .0025; false discovery rate q < 0.05). The groups without reach training did not show the same degree of reduction in diaschisis or activation of the red nucleus. Conclusions. Our results suggest that motor recovery and remodeling of neuronal circuits after capsular stroke depend on the magnitude of the capsular lesion and on the presence or absence of reach training. Task-specific training is strongly indicated only when there is incomplete destruction of the capsular fibers.
Background. Paralysis of the upper limbs from spinal cord injury results in an enormous loss of independence in an individual’s daily life. Meaningful improvement in hand function is rare after 1 year of tetraparesis. Therapeutic developments that result in even modest gains in hand volitional function will significantly affect the quality of life for patients afflicted with high cervical injury. The ability to neuromodulate the lumbosacral spinal circuitry via epidural stimulation in regaining postural function and volitional control of the legs has been recently shown. A key question is whether a similar neuromodulatory strategy can be used to improve volitional motor control of the upper limbs, that is, performance of motor tasks considered to be less "automatic" than posture and locomotion. In this study, the effects of cervical epidural stimulation on hand function are characterized in subjects with chronic cervical cord injury. Objective. Herein we show that epidural stimulation can be applied to the chronic injured human cervical spinal cord to promote volitional hand function. Methods and Results. Two subjects implanted with a cervical epidural electrode array demonstrated improved hand strength (approximately 3-fold) and volitional hand control in the presence of epidural stimulation. Conclusions. The present data are sufficient to suggest that hand motor function in individuals with chronic tetraplegia can be improved with cervical cord neuromodulation and thus should be comprehensively explored as a possible clinical intervention.
Background. The effect of levodopa on postural motor learning in people with Parkinson’s disease is poorly understood. In particular, it is unknown whether levodopa affects improvement in protective postural responses after external perturbations such as a slip or trip, a critical aspect of fall prevention. Objective. Determine the effect of levodopa on postural motor learning in people with Parkinson’s disease. Methods. We assessed improvement in protective postural responses in people with Parkinson’s disease over short-term (1 day) perturbation training on and off levodopa. We also assessed retention and generalization of improvement. Participants were 22 individuals with Parkinson’s disease. The primary outcome was total center of mass (COM) displacement after perturbation. Secondary outcomes assessed first step performance and included margin of stability at first foot contact. Results. People with Parkinson’s disease improved COM displacement (P = .011) and margin of stability (P = .016) over training. Improvements in these outcomes were more pronounced after training while on levodopa than off levodopa. Levodopa State x Training interactions were not observed for other step performance variables (eg, step latency, length, total number of steps). Improvements were retained for 24 hours, and for margin of stability, retention was more pronounced while on levodopa than off (P = .018). Conclusions. Individuals with Parkinson’s disease are able to improve protective postural responses through short-term perturbation training, and improvements were more pronounced when on levodopa for some variables. Perturbation training may be more effective if completed while optimally medicated with levodopa.
Objective. Genetic variations in the dopamine (DA) system are associated with cortical-striatal behavior in multiple populations. This study assessed associations of functional polymorphisms in the ankyrin repeat and kinase domain (ANKK1; Taq1a) and catechol-O-methyltransferase (COMT; Val158Met) genes with behavioral dysfunction following traumatic brain injury (TBI). Participants. This was a prospective study of 90 survivors of severe TBI recruited from a level 1 trauma center. Main measures. The Frontal Systems Behavior Scale, a self- or family report questionnaire evaluating behavior associated with frontal lobe dysfunction, was completed 6 and 12 months postinjury. Depression was measured concurrently with the Patient Health Questionnaire-9. Study participants were genotyped for Val158Met and Taq1a polymorphisms. Results. No statistically significant behavioral differences were observed by Taq1a or Val158Met genotype alone. At 12 months, among those with depression, Met homozygotes (Val158Met) self-reported worse behavior than Val carriers (P = .015), and A2 homozygotes (Taq1a) self-reported worse behavior than A1 carriers (P = .028) in bivariable analysis. Multivariable models suggest an interaction between depression and genetic variation with behavior at 12 months post-TBI, and descriptive analysis suggests that carriage of both risk alleles may contribute to worse behavioral performance than carriage of either risk allele alone. Conclusion. In the context of depression, Val158Met and Taq1a polymorphisms are individually associated with behavioral dysfunction 12 months following severe TBI, with preliminary evidence suggesting cumulative, or perhaps epistatic, effects of COMT and ANKK1 on behavioral dysfunction.
Background. Recent studies show that patients with Parkinson’s disease (PD) and freezing of gait (FOG) experience motor problems outside their gait freezing episodes. Because handwriting is also a sequential movement, it may be affected in PD patients with FOG relative to those without. Objective. The current study aimed to assess the quality of writing in PD patients with and without FOG in comparison to healthy controls (CTs) during various writing tasks. Methods. Handwriting was assessed by the writing of cursive loops on a touch-sensitive writing tablet and by means of the Systematic Screening of Handwriting Difficulties (SOS) test in 30 PD patients with and without freezing and 15 healthy age-matched CTs. The tablet tests were performed at 2 different sizes, either continuously or alternatingly, as indicated by visual target lines. Results. Patients with freezing showed decreased writing amplitudes and increased variability compared with CTs and patients without freezing on the writing tablet tests. Writing problems were present during both tests but were more pronounced during writing at alternating compared with writing at continuous size. Patients with freezing also had a higher total score on the SOS test than patients without freezing and CTs, reflecting more extensive handwriting problems, particularly with writing fluency. Conclusions. Writing is more severely affected in PD patients with FOG than in those without FOG. These results indicate that deficient movement sequencing and adaptation is a generic problem in patients with FOG.
Background. Alzheimer’s disease (AD) is a highly prevalent neurodegenerative disorder. Rate of decline and functional restoration in AD greatly depend on the capacity for neural plasticity within residual neural tissues; this is at least partially influenced by polymorphisms in genes that determine neural plasticity, including Apolipoprotein E4 (ApoE4) and synaptosomal-associated protein of 25 kDa (SNAP-25). Objective. We investigated whether correlations could be detected between polymorphisms of ApoE4 and SNAP-25 and the outcome of a multidimensional rehabilitative approach, based on cognitive stimulation, behavioral, and functional therapy (multidimensional stimulation therapy [MST]). Methods. Fifty-eight individuals with mild-to-moderate AD underwent MST for 10 weeks. Neuro-psychological functional and behavioral evaluations were performed blindly by a neuropsychologist at baseline and after 10 weeks of therapy using Mini-Mental State Examination (MMSE), Functional Living Skill Assessment (FLSA), and Neuropsychiatric Inventory (NPI) scales. Molecular genotyping of ApoE4 and SNAP-25 rs363050, rs363039, rs363043 was performed. Results were correlated with MMSE, NPI and FLSA scores by multinomial logistic regression analysis. Results. Polymorphisms in both genes correlated with the outcome of MST for MMSE and NPI scores. Thus, higher overall MMSE scores after rehabilitation were detected in ApoE4 negative compared to ApoE4 positive patients, whereas the SNAP-25 rs363050(G) and rs363039(A) alleles correlated with significant improvements in behavioural parameters. Conclusions. Polymorphisms in genes known to modulate neural plasticity might predict the outcome of a multistructured rehabilitation protocol in patients with AD. These data, although needing confirmation on larger case studies, could help optimizing the clinical management of individuals with AD, for example defining a more intensive treatment in those subjects with a lower likelihood of success.
Background. Performance variability in individuals with aphasia is typically regarded as a nuisance factor complicating assessment and treatment. Objective. We present the alternative hypothesis that intraindividual variability represents a fundamental characteristic of an individual’s functioning and an important biomarker for therapeutic selection and prognosis. Methods. A total of 19 individuals with chronic aphasia participated in a 6-week trial of imitation-based speech therapy. We assessed improvement both on overall language functioning and repetition ability. Furthermore, we determined which pretreatment variables best predicted improvement on the repetition test. Results. Significant gains were made on the Western Aphasia Battery-Revised (WAB) Aphasia Quotient, Cortical Quotient, and 2 subtests as well as on a separate repetition test. Using stepwise regression, we found that pretreatment intraindividual variability was the only predictor of improvement in performance on the repetition test, with greater pretreatment variability predicting greater improvement. Furthermore, the degree of reduction in this variability over the course of treatment was positively correlated with the degree of improvement. Conclusions. Intraindividual variability may be indicative of potential for improvement on a given task, with more uniform performance suggesting functioning at or near peak potential.
Background. Pharyngeal electrical stimulation (PES) appears to promote cortical plasticity and swallowing recovery poststroke. Objective. We aimed to assess clinical effectiveness with longer follow-up. Methods. Dysphagic patients (n = 36; median = 71 years; 61% male) recruited from 3 trial centers within 6 weeks of stroke, received active or sham PES in a single-blinded randomized design via an intraluminal pharyngeal catheter (10 minutes, for 3days). The primary outcome measure was the Dysphagia Severity Rating (DSR) scale (<4, no-mild; ≥4, moderate-severe). Secondary outcomes included unsafe swallows on the Penetration-Aspiration Scale (PAS ≥ 3), times to hospital discharge, and nasogastric tube (NGT) removal. Data were analyzed using logistic regression. Odds/hazard ratios (ORs/HRs) >1 for DSR <4, hospital discharge, and NGT removal and OR <1 for PAS ≥3, indicated favorable outcomes for active PES. Results. Two weeks post–active PES, 11/18 (61%) had DSR <4: OR (95% CI) = 2.5 (0.52, 14). Effects of active versus sham for secondary outcomes included the following: PAS ≥3 at 2 weeks, OR (95% CI) = 0.61 (0.27, 1.4); times to hospital discharge, 39 days versus 52 days, HR (95% CI) = 1.2 (0.55, 2.5); NGT removal 8 versus 14 days, HR (95% CI) = 2.0 (0.51, 7.9); and DSR <4 at 3 months, OR (95% CI) = 0.97 (0.13, 7.0). PES was well tolerated, without adverse effects or associations with serious complications (chest infections/death). Conclusions. Although the direction of observed differences were consistent with PES accelerating swallowing recovery over the first 2 weeks postintervention, suboptimal recruitment prevents definitive conclusions. Our study design experience and outcome data are essential to inform a definitive, multicenter randomized trial.
Background. Individuals with brain impairment (BI) are less active than the general population and have increased risk of chronic disease. Objective. This controlled trial evaluated the efficacy of a physical activity (PA) intervention for community-dwelling adults with BI. Methods. A total of 43 adults with BI (27 male, 16 female; age 38.1 ± 11.9 years; stage of change 1-3) who walked as their primary means of locomotion were allocated to an intervention (n = 23) or control (n = 20) condition. The intervention comprised 10 face-to-face home visits over 12 weeks, including a tailored combination of stage-matched behavior change activities, exercise prescription, community access facilitation, and relapse prevention strategies. The control group received 10 face-to-face visits over 12 weeks to promote sun safety, healthy sleep, and oral health. Primary outcomes were daily activity counts and minutes of moderate-to-vigorous-intensity PA (MVPA) measured with the ActiGraph GT1M at baseline (0 weeks), postintervention (12 weeks) and follow-up (24 weeks). Between-group differences were evaluated for statistical significance using repeated-measures ANOVA. Results. MVPA for the intervention group increased significantly from baseline to 12 weeks (20.8 ± 3.1 to 31.2 ± 3.1 min/d; P = .01), but differences between baseline and 24 weeks were nonsignificant (20.8 ± 3.1 to 25.3 ± 3.2 min/d; P = .28). MVPA changes for the control group were negligible and nonsignificant. Between-group differences for change in MVPA were significant at 12 weeks (P = .03) but not at 24 weeks (P = .49). Conclusion. The 12-week intervention effectively increased adoption of PA in a sample of community-dwelling adults with BI immediately after the intervention but not at follow-up. Future studies should explore strategies to foster maintenance of PA participation.
Background. The positive correlation between therapeutic exercise and memory recovery in cases of ischemia has been extensively studied; however, long-term exercise begun after ischemic neuronal death as a chronic neurorestorative strategy has not yet been thoroughly examined. Objective. The purpose of this study is to investigate possible mechanisms by which exercise ameliorates ischemia-induced memory impairment in the aged gerbil hippocampus after transient cerebral ischemia. Methods. Treadmill exercise was begun 5 days after ischemia-reperfusion (I-R) and lasted for 1 or 4 weeks. The animals were sacrificed 31 days after the induction of ischemia. Changes in short-term memory, as well as the hippocampal expression of markers of cell proliferation, neuroblast differentiation, neurogenesis, myelin and microvessel repair, and growth factors were examined by immunohistochemistry and/or western blots. Results. Four weeks of exercise facilitated memory recovery despite neuronal damage in the stratum pyramidale (SP) of the hippocampal CA1 region and in the polymorphic layer (PoL) of the dentate gyrus (DG) after I-R. Long-term exercise enhanced cell proliferation and neuroblast differentiation in a time-dependent manner, and newly generated mature cells were found in the granule cell layer of the DG, but not in the SP of the CA1 region or in the PoL of the DG. In addition, long-term exercise ameliorated ischemia-induced damage of myelin and microvessels, which was correlated with increased BDNF expression in the CA1 region and the DG. Conclusions. These results suggest that long-term treadmill exercise after I-R can restore memory function through replacement of multiple damaged structures in the ischemic aged hippocampus.
The remarkable scientific and technological advances in the field of cell research have not been translated into viable restorative therapies for brain disorders. In this article, we examine the best available evidence for the clinical efficacy of reconstructive intracerebral transplantation in people with Parkinson’s disease (PD), with the aim of identifying methodological obstacles to the translation process. The major stumbling block is the fact that the potential contributions of people with neural grafts and the effects of the physical and social environment in which they recover have not been adequately investigated and applied to advancing the clinical stages of the research program. We suggest that the biopsychosocial model along with emerging evidence of targeted rehabilitation can provide a useful framework for conducting research and evaluation that will ensure the best possible outcomes following intracerebral transplantation for PD.
Background. Intensive bimanual therapy can improve hand function in children with unilateral spastic cerebral palsy (USCP). We compared the effects of structured bimanual skill training versus unstructured bimanual practice on motor outcomes and motor map plasticity in children with USCP. Objective. We hypothesized that structured skill training would produce greater motor map plasticity than unstructured practice. Methods. Twenty children with USCP (average age 9.5; 12 males) received therapy in a day camp setting, 6 h/day, 5 days/week, for 3 weeks. In structured skill training (n = 10), children performed progressively more difficult movements and practiced functional goals. In unstructured practice (n = 10), children engaged in bimanual activities but did not practice skillful movements or functional goals. We used the Assisting Hand Assessment (AHA), Jebsen-Taylor Test of Hand Function (JTTHF), and Canadian Occupational Performance Measure (COPM) to measure hand function. We used single-pulse transcranial magnetic stimulation to map the representation of first dorsal interosseous and flexor carpi radialis muscles bilaterally. Results. Both groups showed significant improvements in bimanual hand use (AHA; P < .05) and hand dexterity (JTTHF; P < .001). However, only the structured skill group showed increases in the size of the affected hand motor map and amplitudes of motor evoked potentials (P < .01). Most children who showed the most functional improvements (COPM) had the largest changes in map size. Conclusions. These findings uncover a dichotomy of plasticity: the unstructured practice group improved hand function but did not show changes in motor maps. Skill training is important for driving motor cortex plasticity in children with USCP.
Background. Even though lower-limb motor disorders are core features of spastic cerebral palsy (sCP), the relationship with brain lesions remains unclear. Unraveling the relation between gait pathology, lower-limb function, and brain lesions in sCP is complex for several reasons; wide heterogeneity in brain lesions, ongoing brain maturation, and gait depends on a number of primary motor functions/deficits (eg, muscle strength, spasticity). Objective. To use a comprehensive approach combining conventional MRI and diffusion tensor imaging (DTI) in children with sCP above 3 years old to relate quantitative parameters of brain lesions in multiple brain areas to gait performance. Methods. A total of 50 children with sCP (25 bilateral, 25 unilateral involvement) were enrolled. The investigated neuroradiological parameters included the following: (1) volumetric measures of the corpus callosum (CC) and lateral ventricles (LVs), and (2) DTI parameters of the corticospinal tract (CST). Gait pathology and primary motor deficits, including muscle strength and spasticity, were evaluated by 3D gait analysis and clinical examination. Results. In bilateral sCP (n = 25), volume of the LV and the subparts of the CC connecting frontal, (pre)motor, and sensory areas were most related to lower-limb functioning and gait pathology. DTI measures of the CST revealed additional relations with the primary motor deficits (n = 13). In contrast, in unilateral sCP, volumetric (n = 25) and diffusion measures (n = 14) were only correlated to lower-limb strength. Conclusions. These results indicate that the combined influence of multiple brain lesions and their impact on the primary motor deficits might explain a large part of the gait pathology in sCP.
Background and Objective. Favorable prognosis of the upper limb depends on preservation or return of voluntary finger extension (FE) early after stroke. The present study aimed to determine the effects of modified constraint-induced movement therapy (mCIMT) and electromyography-triggered neuromuscular stimulation (EMG-NMS) on upper limb capacity early poststroke. Methods. A total of 159 ischemic stroke patients were included: 58 patients with a favorable prognosis (>10° of FE) were randomly allocated to 3 weeks of mCIMT or usual care only; 101 patients with an unfavorable prognosis were allocated to 3-week EMG-NMS or usual care only. Both interventions started within 14 days poststroke, lasted up until 5 weeks, focused at preservation or return of FE. Results. Upper limb capacity was measured with the Action Research Arm Test (ARAT), assessed weekly within the first 5 weeks poststroke and at postassessments at 8, 12, and 26 weeks. Clinically relevant differences in ARAT in favor of mCIMT were found after 5, 8, and 12 weeks poststroke (respectively, 6, 7, and 7 points; P < .05), but not after 26 weeks. We did not find statistically significant differences between mCIMT and usual care on impairment measures, such as the Fugl-Meyer assessment of the arm (FMA-UE). EMG-NMS did not result in significant differences. Conclusions. Three weeks of early mCIMT is superior to usual care in terms of regaining upper limb capacity in patients with a favorable prognosis; 3 weeks of EMG-NMS in patients with an unfavorable prognosis is not beneficial. Despite meaningful improvements in upper limb capacity, no evidence was found that the time-dependent neurological improvements early poststroke are significantly influenced by either mCIMT or EMG-NMS.
Background. Approximately 60% of patients suffering from acute spinal cord injury (SCI) develop pain within days to weeks after injury, which ultimately persists into chronic stages. To date, the consequences of pain after SCI have been largely examined in terms of interfering with quality of life. Objective. The objective of this study was to examine the effects of pain and pain management on neurological recovery after SCI. Methods. We analyzed clinical data in a prospective multicenter observational cohort study in patients with SCI. Using mixed effects regression techniques, total motor and sensory scores were modelled at 1, 3, 6, and 12 months postinjury. Results. A total of 225 individuals were included in the study (mean age: 45.8 ± 18 years, 80% male). At 1 month postinjury, 28% of individuals with SCI reported at- or below-level neuropathic pain. While pain classification showed no effect on neurological outcomes, individuals administered anticonvulsant medications at 1 month postinjury showed significant reductions in pain intensity (2 points over 1 year; P < .05) and greater recovery in total motor scores (7.3 points over 1 year; P < .05). This drug effect on motor recovery remained significant after adjustment for injury level and injury severity, pain classification, and pain intensity. Conclusion. While initial pain classification and intensity did not reveal an effect on motor recovery following acute SCI, anticonvulsants conferred a significant beneficial effect on motor outcomes. Early intervention with anticonvulsants may have effects beyond pain management and warrant further studies to evaluate the therapeutic effectiveness in human SCI.
Background. Perinatal stroke is the leading cause of hemiparetic cerebral palsy. Motor deficits and their treatment are commonly emphasized in the literature. Sensory dysfunction may be an important contributor to disability, but it is difficult to measure accurately clinically. Objective. Use robotics to quantify position sense deficits in hemiparetic children with perinatal stroke and determine their association with common clinical measures. Methods. Case-control study. Participants were children aged 6 to 19 years with magnetic resonance imaging–confirmed unilateral perinatal arterial ischemic stroke or periventricular venous infarction and symptomatic hemiparetic cerebral palsy. Participants completed a position matching task using an exoskeleton robotic device (KINARM). Position matching variability, shift, and expansion/contraction area were measured with and without vision. Robotic outcomes were compared across stroke groups and controls and to clinical measures of disability (Assisting Hand Assessment) and sensory function. Results. Forty stroke participants (22 arterial, 18 venous, median age 12 years, 43% female) were compared with 60 healthy controls. Position sense variability was impaired in arterial (6.01 ± 1.8 cm) and venous (5.42 ± 1.8 cm) stroke compared to controls (3.54 ± 0.9 cm, P < .001) with vision occluded. Impairment remained when vision was restored. Robotic measures correlated with functional disability. Sensitivity and specificity of clinical sensory tests were modest. Conclusions. Robotic assessment of position sense is feasible in children with perinatal stroke. Impairment is common and worse in arterial lesions. Limited correction with vision suggests cortical sensory network dysfunction. Disordered position sense may represent a therapeutic target in hemiparetic cerebral palsy.
Background. Recent rehabilitation efforts after stroke often focus on increasing walking speed because it is associated with quality of life. For individuals poststroke, propulsive force generated from the paretic limb has been shown to be correlated to walking speed. However, little is known about the relative contribution of the paretic versus the nonparetic propulsive forces to changes in walking speed. Objective. The primary purpose of this study was to determine the contribution of propulsive force generated from each limb to changes in walking speed during speed modulation within a session and as a result of a 12-week training program. Methods. Gait analysis was performed as participants (N = 38) with chronic poststroke hemiparesis walked at their self-selected and faster walking speeds on a treadmill before and after a 12-week gait retraining program. Results. Prior to training, stroke survivors increased nonparetic propulsive forces as the primary mechanism to change walking speed during speed modulation within a session. Following gait training, the paretic limb played a larger role during speed modulation within a session. In addition, the increases in paretic propulsive forces observed following gait training contributed to the increases in the self-selected walking speeds seen following training. Conclusions. Gait retraining in the chronic phase of stroke recovery facilitates paretic limb neuromotor recovery and reduces the reliance on the nonparetic limb’s generation of propulsive force to increase walking speed. These findings support gait rehabilitation efforts directed toward improving the paretic limb’s ability to generate propulsive force.
Background and objective. Prior studies have suggested that after stroke there is a time-limited period of increased responsiveness to training as a result of heightened plasticity—a sensitive period thought to be induced by ischemia itself. Using a mouse model, we have previously shown that most training-associated recovery after a caudal forelimb area (CFA) stroke occurs in the first week and is attributable to reorganization in a medial premotor area (AGm). The existence of a stroke-induced sensitive period leads to the counterintuitive prediction that a second stroke should reopen this window and promote full recovery from the first stroke. To test this prediction, we induced a second stroke in the AGm of mice with incomplete recovery after a first stroke in CFA. Methods. Mice were trained to perform a skilled prehension (reach-to-grasp) task to an asymptotic level of performance, after which they underwent photocoagulation-induced stroke in CFA. After a 7-day poststroke delay, the mice were then retrained to asymptote. We then induced a second stroke in the AGm, and after only a 1-day delay, retrained the mice. Results. Recovery of prehension was incomplete when training was started after a 7-day poststroke delay and continued for 19 days. However, a second focal stroke in the AGm led to a dramatic response to 9 days of training, with full recovery to normal levels of performance. Conclusions. New ischemia can reopen a sensitive period of heightened responsiveness to training and mediate full recovery from a previous stroke.
Background. A thorough understanding of the presence of different upper-limb somatosensory deficits poststroke and the relation with motor performance remains unclear. Additionally, knowledge about the relation between somatosensory deficits and visuospatial neglect is limited. Objective. To investigate the distribution of upper-limb somatosensory impairments and the association with unimanual and bimanual motor outcomes and visuospatial neglect. Methods. A cross-sectional observational study was conducted, including 122 patients within 6 months after stroke (median = 82 days; interquartile range = 57-133 days). Somatosensory measurement included the Erasmus MC modification of the (revised) Nottingham Sensory Assessment (Em-NSA), Perceptual Threshold of Touch (PTT), thumb finding test, 2-point discrimination, and stereognosis subscale of the NSA. Upper-limb motor assessment comprised the Fugl-Meyer assessment, motricity index, Action Research Arm Test, and Adult-Assisting Hand Assessment Stroke. Screening for visuospatial neglect was performed using the Star Cancellation Test. Results. Upper-limb somatosensory impairments were common, with prevalence rates ranging from 21% to 54%. Low to moderate Spearman correlations were found between somatosensory and motor deficits (r = 0.22-0.61), with the strongest associations for PTT (r = 0.56-0.61) and stereognosis (r = 0.51-0.60). Visuospatial neglect was present in 27 patients (22%). Between-group analysis revealed somatosensory deficits that occurred significantly more often and more severely in patients with visuospatial neglect (P < .05). Results showed consistently stronger correlations between motor and somatosensory deficits in patients with visuospatial neglect (r = 0.44-0.78) compared with patients without neglect (r = 0.08-0.59). Conclusions. Somatosensory impairments are common in subacute patients poststroke and are related to motor outcome. Visuospatial neglect was associated with more severe upper-limb somatosensory impairments.
Background: Multiple sclerosis (MS) is associated with balance deficits resulting in falls and impaired mobility. Although rehabilitation has been recommended to address these balance deficits, the extent to which people with MS can learn and retain improvements in postural responses is unknown. Aim: To determine the ability of people with MS to improve postural control with surface perturbation training. Methods: A total of 24 patients with mild MS and 14 age-matched controls underwent postural control training with a set pattern of continuous, forward-backward, sinusoidal, and surface translations provided by a force platform. Postural control was then tested the following day for retention. The primary outcome measures were the relative phase and center-of-mass (CoM) gain between the body CoM and the platform motion. Results: People with MS demonstrated similar improvements in acquiring and retaining changes in the temporal control of the CoM despite significant deficits in postural motor performance at the baseline. Both MS and control groups learned to anticipate the pattern of forward-backward perturbations, so body CoM shifted from a phase-lag (age-matched controls [CS] = –7.1 ± 1.3; MS = –12.9 ± 1.0) toward a phase-lead (CS = –0.7 ± 1.8; MS = –6.1 ± 1.4) relationship with the surface oscillations. However, MS patients were not able to retain the changes in the spatial control of the CoM acquired during training. Conclusions: People with MS have the capacity to improve use of a feed-forward postural strategy with practice and retain the learned behavior for temporal not spatial control of CoM, despite their significant postural response impairments.
Background and Objectives. The onset of pervasive sleep-wake disturbances associated with traumatic brain injury (TBI) is poorly understood. This study aimed to (a) determine the feasibility of using polysomnography in patients in the acute, hospitalized stage of severe TBI and (b) explore sleep quality and sleep architecture during this stage of recovery, compared to patients with other traumatic injuries. Methods. A cross-sectional case-control design was used. We examined the sleep of 7 patients with severe TBI (17-47 years; 20.3 ± 15.0 days postinjury) and 6 patients with orthopedic and/or spinal cord injuries (OSCI; 19-58 years; 16.9 ± 4.9 days postinjury). One night of ambulatory polysomnography was performed at bedside. Results. Compared to OSCI patients, TBI patients showed a significantly longer duration of nocturnal sleep and earlier nighttime sleep onset. Sleep efficiency was low and comparable in both groups. All sleep stages were observed in both groups with normal proportions according to age. Conclusion. Patients in the acute stage of severe TBI exhibit increased sleep duration and earlier sleep onset, suggesting that the injured brain enhances sleep need and/or decreases the ability to maintain wakefulness. As poor sleep efficiency could compromise brain recovery, further studies should investigate whether strategies known to optimize sleep in healthy individuals are efficacious in acute TBI. While there are several inherent challenges, polysomnography is a useful means of examining sleep in the early stage of recovery in patients with severe TBI.
Background. Robots designed for rehabilitation of the upper extremity after stroke facilitate high rates of repetition during practice of movements and record precise kinematic data, providing a method to investigate motor recovery profiles over time. Objective. To determine how motor recovery profiles during robotic interventions provide insight into improving clinical gains. Methods. A convenience sample (n = 22), from a larger randomized control trial, was taken of chronic stroke participants completing 12 sessions of arm therapy. One group received 60 minutes of robotic therapy (Robot only) and the other group received 45 minutes on the robot plus 15 minutes of translation-to-task practice (Robot + TTT). Movement time was assessed using the robot without powered assistance. Analyses (ANOVA, random coefficient modeling [RCM] with 2-term exponential function) were completed to investigate changes across the intervention, between sessions, and within a session. Results. Significant improvement (P < .05) in movement time across the intervention (pre vs post) was similar between the groups but there were group differences for changes between and within sessions (P < .05). The 2-term exponential function revealed a fast and slow component of learning that described performance across consecutive blocks. The RCM identified individuals who were above or below the marginal model. Conclusions. The expanded analyses indicated that changes across time can occur in different ways but achieve similar goals and may be influenced by individual factors such as initial movement time. These findings will guide decisions regarding treatment planning based on rates of motor relearning during upper extremity stroke robotic interventions.
Neuropathic pain is a debilitating consequence of spinal cord injury (SCI) that correlates with sensory fiber sprouting. Recent data indicate that exercise initiated early after SCI prevents the development of allodynia and modulated nociceptive afferent plasticity. This study determined if delaying exercise intervention until pain is detected would similarly ameliorate established SCI-induced pain. Adult, female Sprague-Dawley rats with a C5 unilateral contusion were separated into SCI allodynic and SCI non-allodynic cohorts at 14 or 28 days postinjury when half of each group began exercising on automated running wheels. Allodynia, assessed by von Frey testing, was not ameliorated by exercise. Furthermore, rats that began exercise with no allodynia developed paw hypersensitivity within 2 weeks. At the initiation of exercise, the SCI Allodynia group displayed marked overlap of peptidergic and non-peptidergic nociceptive afferents in the C7 and L5 dorsal horn, while the SCI No Allodynia group had scant overlap. At the end of 5 weeks of exercise both the SCI Allodynia and SCI No Allodynia groups had extensive overlap of the 2 c-fiber types. Our findings show that exercise therapy initiated at early stages of allodynia is ineffective at attenuating neuropathic pain, but rather that it induces allodynia-aberrant afferent plasticity in previously pain-free rats. These data, combined with our previous results, suggest that there is a critical therapeutic window when exercise therapy may be effective at treating SCI-induced allodynia and that there are postinjury periods when exercise can be deleterious.
Background. Neurorehabilitation efforts have been limited in their ability to restore walking function after stroke. Recent work has demonstrated proof-of-concept for a functional electrical stimulation (FES)–based combination therapy designed to improve poststroke walking by targeting deficits in paretic propulsion. Objectives. To determine the effects on the energy cost of walking (EC) and long-distance walking ability of locomotor training that combines fast walking with FES to the paretic ankle musculature (FastFES). Methods. Fifty participants >6 months poststroke were randomized to 12 weeks of gait training at self-selected speeds (SS), fast speeds (Fast), or FastFES. Participants’ 6-minute walk test (6MWT) distance and EC at comfortable (EC-CWS) and fast (EC-Fast) walking speeds were measured pretraining, posttraining, and at a 3-month follow-up. A reduction in EC-CWS, independent of changes in speed, was the primary outcome. Group differences in the number of 6MWT responders and moderation by baseline speed were also evaluated. Results. When compared with SS and Fast, FastFES produced larger reductions in EC (Ps ≤.03). FastFES produced reductions of 24% and 19% in EC-CWS and EC-Fast (Ps <.001), respectively, whereas neither Fast nor SS influenced EC. Between-group 6MWT differences were not observed; however, 73% of FastFES and 68% of Fast participants were responders, in contrast to 35% of SS participants. Conclusions. Combining fast locomotor training with FES is an effective approach to reducing the high EC of persons poststroke. Surprisingly, differences in 6MWT gains were not observed between groups. Closer inspection of the 6MWT and EC relationship and elucidation of how reduced EC may influence walking-related disability is warranted.
Background. Motor-learning interventions may improve hand function in children with unilateral cerebral palsy (UCP) but with inconsistent outcomes across participants. Objective. To examine if pre-intervention brain imaging predicts benefit from bimanual intervention. Method. Twenty children with UCP with Manual Ability Classification System levels I to III, aged 7-16 years, participated in an intensive bimanual intervention. Assessments included the Assisting Hand Assessment (AHA), Jebsen Taylor Test of Hand Function (JTTHF) and Children’s Hand Experience Questionnaire (CHEQ) at baseline (T1), completion (T2) and 8-10 weeks post-intervention (T3). Imaging at baseline included conventional structural (radiological score), functional (fMRI) and diffusion tensor imaging (DTI). Results. Improvements were seen across assessments; AHA (P = 0.04), JTTHF (P < .001) and CHEQ (P < 0.001). Radiological score significantly correlated with improvement at T2; AHA (r = .475) and CHEQ (r = .632), but negatively with improvement on unimanual measures at T3 (JTTFH r = –.514). fMRI showed negative correlations between contralesional brain activation when moving the affected hand and AHA improvements (T2: r = –.562, T3: r = –0.479). Fractional Anisotropy in the affected posterior limb of the internal capsule correlated negatively with increased bimanual use on CHEQ at T2 (r = –547) and AHA at T3 (r = –.656). Conclusions. Children with greater structural, functional and connective brain damage showed enhanced responses to bimanual intervention. Baseline imaging may identify parameters predicting response to intervention in children with UCP.
Background and objective. Stroke is a leading cause of long-term disability. Currently, there are no consistently effective rehabilitative treatments for chronic stroke patients. Our recent studies demonstrate that vagus nerve stimulation (VNS) paired with rehabilitative training improves recovery of function in multiple models of stroke. Here, we evaluated the ability of VNS paired with rehabilitative training to improve recovery of forelimb strength when initiated many weeks after a cortical and subcortical ischemic lesion in subjects with stable, chronic motor deficits. Methods. Rats were trained to perform an automated, quantitative measure of voluntary forelimb strength. Once proficient, rats received injections of endothelin-1 to cause a unilateral cortical and subcortical ischemic lesion. Then, 6 weeks after the lesion, rats underwent rehabilitative training paired with VNS (Paired VNS; n = 10), rehabilitative training with equivalent VNS delivered 2 hours after daily rehabilitative training (Delayed VNS; n = 10), or rehabilitative training without VNS (Rehab, n = 9). Results. VNS paired with rehabilitative training significantly improved recovery of forelimb function compared with control groups. The Paired VNS group displayed an 86% recovery of strength, the Rehab group exhibited 47% recovery, and the Delayed VNS group exhibited 42% recovery. Improvement in forelimb function was sustained in the Paired VNS group after the cessation of stimulation, potentially indicating lasting benefits. No differences in intensity of rehabilitative training, lesion size, or MAP-2 expression were observed between groups. Conclusion. VNS paired with rehabilitative training confers significantly greater recovery of forelimb function after chronic ischemic stroke in rats.
Background. The extent to which the upper-limb flexor synergy constrains or compensates for arm motor impairment during reaching is controversial. This synergy can be quantified with a minimal marker set describing movements of the arm-plane. Objectives. To determine whether and how (a) upper-limb flexor synergy in patients with chronic stroke contributes to reaching movements to different arm workspace locations and (b) reaching deficits can be characterized by arm-plane motion. Methods. Sixteen post-stroke and 8 healthy control subjects made unrestrained reaching movements to targets located in ipsilateral, central, and contralateral arm workspaces. Arm-plane, arm, and trunk motion, and their temporal and spatial linkages were analyzed. Results. Individuals with moderate/severe stroke used greater arm-plane movement and compensatory trunk movement compared to those with mild stroke and control subjects. Arm-plane and trunk movements were more temporally coupled in stroke compared with controls. Reaching accuracy was related to different segment and joint combinations for each target and group: arm-plane movement in controls and mild stroke subjects, and trunk and elbow movements in moderate/severe stroke subjects. Arm-plane movement increased with time since stroke and when combined with trunk rotation, discriminated between different subject groups for reaching the central and contralateral targets. Trunk movement and arm-plane angle during target reaches predicted the subject group. Conclusions. The upper-limb flexor synergy was used adaptively for reaching accuracy by patients with mild, but not moderate/severe stroke. The flexor synergy, as parameterized by the amount of arm-plane motion, can be used by clinicians to identify levels of motor recovery in patients with stroke.
Background. Poststroke lower-limb spasticity (LLS) has been shown to degrade standing balance control by disrupting the temporal synchronization between individual limb centers of pressure (COPs). Time-varying changes in standing balance control associated with alterations in the extent of LLS have yet to be documented and are important to informing treatment strategies to improve such functional outcomes. Objective. The present work aimed to understand the natural recovery of standing balance control among stroke survivors with LLS using limb-specific indices of standing balance control. Furthermore, we sought to understand if time-varying changes in LLS were associated with alterations in standing balance control. Methods. A retrospective analysis of 92 participants was performed; 47 participants never exhibited LLS during the study (No_LLS), and 45 participants exhibited LLS during at least 1 testing session (LLS). Quiet standing for a duration of 30 s on 2 force platforms was recorded. Temporal synchrony and spatial symmetry of COP displacements were assessed, along with interlimb weight-bearing symmetry. Results. All variables, except spatial symmetry, indicated initial improvement followed by deceleration in the rate of balance control recovery. Limb-specific measures indicated that individuals with LLS exhibited deficits in balance control. The recovery trajectories were not different between groups, suggesting a similar rate, but reduced extent, of balance control recovery among the LLS relative to the No_LLS group. Only temporal synchrony was altered by time-varying changes in spasticity. Conclusions. The present results suggest that the reduction in spasticity may be beneficial to balance control recovery.
Background. Paresis in stroke is largely a result of damage to descending corticospinal and corticobulbar pathways. Recovery of paresis predominantly reflects the impact on the neural consequences of this white matter lesion by reactive neuroplasticity (mechanisms involved in spontaneous recovery) and experience-dependent neuroplasticity, driven by therapy and daily experience. However, both theoretical considerations and empirical data suggest that type of stroke (large vessel distribution/lacunar infarction, hemorrhage), locus and extent of infarction (basal ganglia, right-hemisphere cerebral cortex), and the presence of leukoaraiosis or prior stroke might influence long-term recovery of walking ability. In this secondary analysis based on the 408 participants in the Locomotor Experience Applied Post-Stroke (LEAPS) study database, we seek to address these possibilities. Methods. Lesion type, locus, and extent were characterized by the 2 neurologists in the LEAPS trial on the basis of clinical computed tomography and magnetic resonance imaging scans. A series of regression models was used to test our hypotheses regarding the effects of lesion type, locus, extent, and laterality on 2- to 12-month change in gait speed, controlling for baseline gait speed, age, and Berg Balance Scale score. Results. Gait speed change at 1 year was significantly reduced in participants with basal ganglia involvement and prior stroke. There was a trend toward reduction of gait speed change in participants with lacunar infarctions. The presence of right-hemisphere cortical involvement had no significant impact on outcome. Conclusions. Type, locus, and extent of lesion, and the loss of substrate for neuroplastic effect as a result of prior stroke may affect long-term outcome of rehabilitation of hemiparetic gait.
Background. Traumatic brain injury (TBI) has been associated with altered microstructural organization of white matter (WM) and reduced gray matter (GM). Although disrupted WM organization has been linked to poorer motor performance, the predictive value of GM atrophy for motor impairments in TBI remains unclear. Objective. Here, we investigated TBI-induced GM volumetric abnormalities and uniquely examined their relationship with bimanual motor impairments. Methods. 22 moderate to severe TBI patients (mean age = 25.9 years, standard deviation [SD] = 4.9 years; time since injury = 4.7 years, SD = 3.7 years) and 27 age- and gender-matched controls (mean age = 23.4 years; SD = 3.8 years) completed bimanual tasks and a structural magnetic resonance imaging scan. Cortical and subcortical GM volumes were extracted and compared between groups using FreeSurfer. The association between bimanual performance and GM volumetric measures was investigated using partial correlations. Results. Relative to controls, patients performed significantly poorer on the bimanual tasks and demonstrated significantly smaller total GM as well as overall and regional subcortical GM. However, the groups did not show significant differences in regional cortical GM volume. The majority of the results remained significant even after excluding TBI patients with focal lesions, suggesting that TBI-induced volume reductions were predominantly caused by diffuse injury. Importantly, atrophy of the thalamus, putamen, and pallidum correlated significantly with poorer bimanual performance within the TBI group. Conclusions. Our results reveal that GM atrophy is associated with motor impairments in TBI, providing new insights into the etiology of motor control impairments following brain trauma.
Background. Walking while performing another task (eg, talking) is challenging for many stroke survivors, yet its neural basis are not fully understood. Objective. To investigate prefrontal cortex activation and its relationship to gait measures while walking under single-task (ST) and dual-task (DT) conditions (ie, walking while simultaneously performing a cognitive task) in stroke survivors. Methods. We acquired near-infrared spectroscopy (NIRS) data from the prefrontal cortex during treadmill walking in ST and DT conditions in chronic stroke survivors and healthy controls. We also acquired functional magnetic resonance imaging (fMRI) and NIRS during simulated walking under these conditions. Results. NIRS revealed increased oxygenated hemoglobin concentration in DT-walking compared with ST-walking for both groups. For simulated walking, NIRS showed a significant effect of group and group x task, being greater on both occasions, in stroke survivors. A greater increase in brain activation observed from ST to DT walking/ simulated walking was related to a greater change in motor performance in stroke survivors. fMRI revealed increased activity during DT relative to ST conditions in stroke patients in areas including the inferior temporal gyri, superior frontal gyri and cingulate gyri bilaterally, and the right precentral gyrus. The DT-related increase in fMRI activity correlated with DT-related change in behavior in stroke participants in the bilateral inferior temporal gyrus, left cingulate gyrus, and left frontal pole. Conclusion. Our results provide novel evidence that enhanced brain activity changes relate to dual task motor decrements.
Background. While recent clinical trials involving robot-assisted therapy have failed to show clinically significant improvement versus conventional therapy, it is possible that a broader strategy of intensive therapy—to include robot-assisted rehabilitation—may yield clinically meaningful outcomes. Objective. To test the immediate and sustained effects of intensive therapy (robot-assisted therapy plus intensive conventional therapy) on outcomes in a chronic stroke population. Methods. A multivariate mixed-effects model adjusted for important covariates was established to measure the effect of intensive therapy versus usual care. A total of 127 chronic stroke patients from 4 Veterans Affairs medical centers were randomized to either robot-assisted therapy (n = 49), intensive comparison therapy (n = 50), or usual care (n = 28), in the VA-ROBOTICS randomized clinical trial. Patients were at least 6 months poststroke, of moderate-to-severe upper limb impairment. The primary outcome measure was the Fugl-Meyer Assessment at 12 and 36 weeks. Results. There was significant benefit of intensive therapy over usual care on the Fugl-Meyer Assessment at 12 weeks with a mean difference of 4.0 points (95% CI = 1.3-6.7); P = .005; however, by 36 weeks, the benefit was attenuated (mean difference 3.4; 95% CI = –0.02 to 6.9; P = .05). Subgroup analyses showed significant interactions between treatment and age, treatment and time since stroke. Conclusions. Motor benefits from intensive therapy compared with usual care were observed at 12 and 36 weeks posttherapy; however, this difference was attenuated at 36 weeks. Subgroups analysis showed that younger age, and a shorter time since stroke were associated with greater immediate and long-term improvement of motor function.
Background. Previous studies have demonstrated improved neurobehavioral outcomes when prosthesis users learn task-specific behaviors by imitating movements of prosthesis users (matched limb) compared with intact limbs (mismatched limb). Objective. This study is the first to use a unique combination of neurophysiological and task performance methods to investigate prosthetic device training strategies from a cognitive motor control perspective. Intact nonamputated prosthesis users (NAPUs) donned specially adapted prosthetic devices to simulate the wrist and forearm movement that persons with transradial limb loss experience. The hypothesis is that NAPUs trained with matched limb imitation would show greater engagement of parietofrontal regions and reduced movement variability compared with their counterparts trained with a mismatched limb. Methods. Training elapsed over 3 days comprised alternating periods of video demonstration observation followed by action imitation. At the beginning and end of the training protocol, participants performed a cued movement paradigm while electroencephalography and electrogoniometry data were collected to track changes in cortical activity and movement variability, respectively. Results. Matched limb participants showed greater engagement of motor-related areas while mismatched limb participants showed greater engagement of the parietooccipital system. Matched limb participants also showed lower movement variability. Conclusions. These results indicate that the type of limb imitated influences neural and behavioral strategies for novel prosthetic device usage. This finding is important, as customary prosthetic rehabilitation with intact therapists involves mismatched limb imitation that may exacerbate challenges in adapting to new motor patterns demanded by prosthesis use.
Background. Clinical trials in spinal cord injury (SCI) primarily rely on simplified outcome metrics (ie, speed, distance) to obtain a global surrogate for the complex alterations of gait control. However, these assessments lack sufficient sensitivity to identify specific patterns of underlying impairment and to target more specific treatment interventions. Objective. To disentangle the differential control of gait patterns following SCI beyond measures of time and distance. Methods. The gait of 22 individuals with motor-incomplete SCI and 21 healthy controls was assessed using a high-resolution 3-dimensional motion tracking system and complemented by clinical and electrophysiological evaluations applying unbiased multivariate analysis. Results. Motor-incomplete SCI patients showed varying degrees of spinal cord integrity (spinal conductivity) with severe limitations in walking speed and altered gait patterns. Principal component (PC) analysis applied on all the collected data uncovered robust coherence between parameters related to walking speed, distortion of intralimb coordination, and spinal cord integrity, explaining 45% of outcome variance (PC 1). Distinct from the first PC, the modulation of gait-cycle variables (step length, gait-cycle phases, cadence; PC 2) remained normal with respect to regained walking speed, whereas hip and knee ranges of motion were distinctly altered with respect to walking speed (PC 3). Conclusions. In motor-incomplete SCI, distinct clusters of discretely controlled gait parameters can be discerned that refine the evaluation of gait impairment beyond outcomes of walking speed and distance. These findings are specifically different from that in other neurological disorders (stroke, Parkinson) and are more discrete at targeting and disentangling the complex effects of interventions to improve walking outcome following motor-incomplete SCI.
Background. The Neuromuscular Recovery Scale (NRS) was developed by researchers and clinicians to functionally classify people with spinal cord injury (SCI) by measuring functionally relevant motor tasks without compensation. Previous studies established strong interrater and test-retest reliability and validity of the scale. Objective. To determine responsiveness of the NRS, a version including newly added upper-extremity items, in an outpatient rehabilitation setting. Methods. Assessments using the NRS and 6 other instruments were conducted at enrollment and discharge from a locomotor training program for 72 outpatients with SCI classified as American Spinal Injury Association Impairment Scale grades A to D (International Standards for Neurological Classification of Spinal Cord Injury). Mixed-model t statistics for instruments were calculated and adjusted for confounding factors (eg, sample size, demographic variables) for all patients and subgroups stratified by injury level and/or severity. The resulting adjusted response means (ARMs) and 95% confidence intervals (CIs) were used to determine responsiveness, and significant differences between instruments were identified with pairwise comparisons. Results. The NRS was significantly responsive for SCI outpatients (ARM = 1.05; CI = 0.75-1.35). Changes in motor function were detected across heterogeneous groups. Regardless of injury level or severity, the responsiveness of the NRS was equal to, and often significantly exceeded, the responsiveness of other instruments. Conclusions. The NRS is a responsive measure that detects change in motor function during outpatient neurorehabilitation for SCI. There is potential utility for its application in randomized controlled trials and as a measure of clinical recovery across diverse SCI populations.
Previous studies have shown that multiple sessions of reach training lead to long-term improvements in movement time and smoothness in individuals post-stroke. Yet such long-term training regimens are often difficult to implement in actual clinical settings. In this study, we evaluated the long-term and generalization effects of short-duration and intensive reach training in 16 individuals with chronic stroke and mild to moderate impairments. Participants performed 2 sessions of unassisted intensive reach training, with 600 movements per session, and with display of performance-based feedback after each movement. The participants’ trunks were restrained with a belt to avoid compensatory movements. Training resulted in significant and durable (1 month) improvements in movement time (20.4% on average) and movement smoothness (22.7% on average). The largest improvements occurred in individuals with the largest initial motor impairments. In addition, training induced generalization to nontrained targets, which persisted in 1-day and in 1-month retention tests. Finally, there was a significant improvement in the Box and Block test from baseline to 1-month retention test (23% on average). Thus, short-duration and intensive reach training can lead to generalized and durable benefits in individuals with chronic stroke and mild to moderate impairments.
Objective. To examine the efficacy of the modified Story Memory Technique (mSMT) to improve learning (ie, acquisition) and memory in participants with TBI. The mSMT is a behavioral intervention that teaches context and imagery to facilitate learning within 10 sessions over 5 weeks. Methods. A total of 69 participants with moderate-severe Traumatic Brain Injury (TBI), 35 in the treatment group and 34 in the placebo control group, completed this double-blind, placebo-controlled randomized clinical trial. A baseline neuropsychological assessment was administered, including questionnaires assessing everyday memory. Repeat assessments were conducted immediately posttreatment and 6 months following treatment. Participants in the treatment group were randomly assigned to a booster session or a non–booster session group after completion of treatment with the mSMT to examine the efficacy of monthly booster sessions in facilitating the treatment effect over time. Results. The treatment group demonstrated significant improvement on a prose memory task relative to the placebo group posttreatment (2 = 0.064 medium effect). Similar results were noted on objective measures of everyday memory, specifically prospective memory (Cohen’s w = 0.43, medium effect), and family report of disinhibition in daily life (2 = 0.046, medium effect). Conclusion. The mSMT is effective for improving learning and memory in TBI. Classification of evidence. Based on widely accepted classification systems for treatment study design, this study provides class I evidence that the mSMT behavioral intervention improves both objective memory and everyday memory in persons with TBI over 5 weeks. Thus, this study extends the evidence for efficacy of the treatment protocol to a sample of persons with TBI.
Background. Use of rehabilitation technology, such as (electro)mechanical devices or robotics, could partly relieve the increasing strain on stroke rehabilitation caused by an increasing prevalence of stroke. Arm support (AS) training showed improvement of unsupported arm function in chronic stroke. Objective. To examine the effect of weight-supported arm training combined with computerized exercises on arm function and capacity, compared with dose-matched conventional reach training in subacute stroke patients. Methods. In a single-blind, multicenter, randomized controlled trial, 70 subacute stroke patients received 6 weeks of training with either an AS device combined with computerized exercises or dose-matched conventional training (CON). Arm function was evaluated pretraining and posttraining by Fugl-Meyer assessment (FM), maximal reach distance, Stroke Upper Limb Capacity Scale (SULCS), and arm pain via Visual Analogue Scale, in addition to perceived motivation by Intrinsic Motivation Inventory posttraining. Results. FM and SULCS scores and reach distance improved significantly within both groups. These improvements and experienced pain did not differ between groups. The AS group reported higher interest/enjoyment during training than the CON group. Conclusions. AS training with computerized exercises is as effective as conventional therapy dedicated to the arm to improve arm function and activity in subacute stroke rehabilitation, when applied at the same dose.
Background. Little information exists about longitudinal changes in spatiotemporal gait asymmetry during rehabilitation, despite it being a common goal. Objectives. To describe longitudinal changes in spatiotemporal gait asymmetry over rehabilitation and examine relationships with changes in other poststroke impairments. Methods. Retrospective chart reviews were conducted for 71 stroke rehabilitation inpatients. Admission and discharge measures of spatiotemporal symmetry, velocity, motor impairment, mobility and balance were extracted and change scores were calculated. Relationships between changes in spatiotemporal symmetry and other change scores were investigated with Spearman correlations. Individuals were divided into four groups (worse, no change-symmetric, no change-asymmetric, improved) based on (1) symmetry/asymmetry at admission and (2) symmetry change scores >minimal detectable change. Differences in change scores between groups were investigated with analyses of covariance using the admission value as a covariate. Results. At admission, 59% and 49% of individuals were asymmetric in swing time and step length, respectively. Of these individuals, 21% and 14% improved swing symmetry or step symmetry, respectively. In contrast, 30% improved gait velocity, 62% improved functional balance and 73% improved functional mobility. Associations between change in swing symmetry and change in paretic limb weight bearing in standing and change in step symmetry and change in velocity were significant. There were no significant differences in change scores between the symmetry groups. Conclusions. The majority of asymmetric stroke patients did not improve spatiotemporal asymmetry during rehabilitation despite the fact that velocity, balance and functional mobility improved. Future work should investigate other factors associated with improved spatiotemporal symmetry and interventions to specifically improve it.
Background. Transplants of cellular grafts expressing a combination of 2 neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) have been shown to promote and enhance locomotor recovery in untrained spinalized cats. Based on the time course of recovery and the absence of axonal growth through the transplants, we hypothesized that recovery was due to neurotrophin-mediated plasticity within the existing locomotor circuitry of the lumbar cord. Since BDNF and NT-3 have different effects on axonal sprouting and synaptic connectivity/strengthening, it becomes important to ascertain the contribution of each individual neurotrophins to recovery. Objective. We studied whether BDNF or NT-3 only producing cellular grafts would be equally effective at restoring locomotion in untrained spinal cats. Methods. Rat fibroblasts secreting one of the 2 neurotrophins were grafted into the T12 spinal transection site of adult cats. Four cats in each group (BDNF alone or NT-3 alone) were evaluated. Locomotor recovery was tested on a treadmill at 3 and 5 weeks post-transection/grafting. Results. Animals in both groups were capable of plantar weight-bearing stepping at speed up to 0.8 m/s as early as 3 weeks and locomotor capabilities were similar at 3 and 5 weeks for both types of graft. Conclusions. Even without locomotor training, either BDNF or NT-3 only producing grafts promote locomotor recovery in complete spinal animals. More clinically applicable delivery methods need to be developed.
Background. Somatosensory stimulation (SS) is a potential adjuvant to stroke rehabilitation, but the effect on function needs further investigation. Objective. To explore the effect of combining SS with task-specific training (TST) on upper limb function and arm use in chronic stroke survivors and determine underlying mechanisms. Methods. In this double-blinded randomized controlled trial (ISRCTN 05542931), 33 patients (mean 37.7 months poststroke) were block randomized to 2 groups: active or sham SS. They received 12 sessions of 2 hours of SS (active or sham) to all 3 upper limb nerves immediately before 30 minutes of TST. The primary outcome was the Action Research Arm Test (ARAT) score. Secondary outcomes were time to perform the ARAT, Fugl-Meyer Assessment score (FM), Motor Activity Log (MAL), and Goal Attainment Scale (GAS). Underlying mechanisms were explored using transcranial magnetic stimulation stimulus–response curves and intracortical inhibition. Outcomes were assessed at baseline, immediately following the intervention (mean 2 days), and 3 and 6 months (mean 96 and 190 days) after the intervention. Results. The active group (n = 16) demonstrated greater improvement in ARAT score and time immediately postintervention (between-group difference; P < .05), but not at 3- or 6-month follow-ups (P > .2). Within-group improvements were seen for both groups for ARAT and GAS, but for the active group only for FM and MAL (P < .05). Corticospinal excitability did not change. Conclusions. Long-lasting improvements in upper limb function were observed following TST. Additional benefit of SS was seen immediately post treatment, but did not persist and the underlying mechanisms remain unclear.
Background. Intrathecal baclofen (ITB) bolus injection effectively decreases spinal excitability but the impact on lower limb muscle activation during gait has not been thoroughly investigated. Objective. Examine activation of medial gastrocnemius (MG) and tibialis anterior (TA) muscles during gait before and after ITB bolus injection in patients with resting hypertonia after acquired brain injury. Methods. Lower extremity Ashworth score, temporospatial gait parameters, characteristics of the linear relationship between electromyogram (EMG) and lengthening velocity (LV) in MG during stance, and the duration and magnitude of TA-MG coactivation were assessed before and at 2, 4, and 6 hours after a 50-µg ITB injection via lumbar puncture in 8 hemorrhagic stroke and 11 traumatic brain injury subjects. Results. Temporospatial gait parameters did not significantly differ across the evaluation points (P ≥ .170). However, Ashworth score (P < .001), frequency and gain of significant positive EMG-LV slope (P ≤ .020), and duration of TA-MG coactivation (P ≤ .013) significantly decreased in the more-affected leg after ITB bolus. EMG changes were not significantly different between patients who did (n = 10) and did not (n = 9) increase gait speed after the injection. The timing of the largest decrease in Ashworth score and the largest decrease in EMG parameters coincided in 36% of cases, on average. Conclusions. ITB bolus injection alters the activation of MG and TA during gait. However, the changes in muscle activation are not closely related to the changes in gait speed or resting muscle hypertonia. The analysis of ankle muscle activation during gait better characterizes the response to ITB bolus injection than gait kinematics.
Background. Impaired trunk motor control is common after stroke. Combining transcutaneous electrical nerve stimulation (TENS) with task-related trunk training (TRTT) has been shown to enhance the recovery of lower limb motor function. Objective. This study investigated whether combining TENS with TRTT would enhance trunk control after stroke. Methods. Thirty-seven subjects with stroke were recruited into a randomized controlled clinical trial. Subjects were randomly assigned to any one of the three 6-week home-based training groups: (1) TENS + TRTT, (2) placebo TENS + TRTT, or (3) control without active training. The outcome measures included isometric peak trunk flexion torque and extension torque; forward seated and lateral seated reaching distance to the affected and unaffected side; and Trunk Impairment Scale (TIS) scores. All outcome measures were assessed at baseline, after 3 and 6 weeks of training, and 4 weeks after training ended at follow-up. Results. Both the TENS + TRTT and the placebo-TENS + TRTT groups had significantly greater improvements in isometric peak trunk flexion torque and extension torque, lateral seated reaching distance to affected and unaffected side, and TIS score than the control group after 3 weeks of training. The TENS + TRTT group had significantly greater and earlier improvement in its mean TIS score than the other 2 groups. Conclusions. Home-based TRTT is effective for improving trunk muscle strength, sitting functional reach and trunk motor control after stroke in subjects without somatosensory deficits. The addition of TENS to the trunk augments the effectiveness of the exercise in terms of TIS scores within the first 3 weeks of training.
Background: Static posture imbalance and gait dysfunction are common in individuals with multiple sclerosis (MS). Although the impact of strength and static balance on walking has been examined, the impact of dynamic standing balance on walking in MS remains unclear. Objective: To determine the impact of dynamic balance, static balance, sensation, and strength measures on walking in individuals with MS. Methods: Fifty-two individuals with MS (27 women; 26 relapsing-remitting; mean age = 45.6 ± 10.3 years; median Expanded Disability Status Scale score = 3.5) participated in posturography testing (Kistler-9281 force plate), hip flexion, hip extension, ankle dorsiflexion strength (Microfet2 hand-held dynamometer), sensation (Vibratron II), and walk velocity (Optotrak Motion Analysis System). Analyses included, Mann-Whitney, Spearman correlation coefficients, and multiple regression. Results: All measures were abnormal in individuals with MS when compared with norms (P < .05). Static balance (eyes open, feet together [EOFT]), anterior-posterior (AP) dynamic sway, and hip extension strength were strongly correlated with walking velocity (AP sway r = 0.68; hip extension strength r = 0.73; EOFT r = –0.40). Together, AP dynamic sway (r = 0.71; P < .001), hip extension strength (r = 0.54; P < .001), and EOFT static balance (r = –0.41; P = .01) explained more than 70% of the variance in walking velocity (P < .001). Conclusions: AP dynamic sway affects walking performance in MS. A combined evaluation of dynamic balance, static balance, and strength may lead to a better understanding of walking mechanisms and the development of strategies to improve walking.
Background. The growing social emergency represented by Alzheimer’s disease (AD) and the lack of medical treatments able to modify the disease course have kindled the interest in nonpharmacological therapies. Objective. We introduced a novel nonpharmacological approach for people with AD (PWA) named Multidimensional Stimulation group Therapy (MST) to improve PWA condition in different disease domains: cognition, behavior, and motor functioning. Methods. Enrolling 60 PWA in a mild to moderate stage of the disease, we evaluated the efficacy of MST with a randomized-controlled study. Neuropsychological and neurobehavioral measures and functional magnetic resonance imaging (fMRI) data were considered as outcome measures. Results. The following significant intervention-related changes were observed: reduction in Neuropsychiatric Inventory scale score, improvement in language and memory subscales of Alzheimer’s Disease Assessment Scale–Cognitive subscale, and increased fMRI activations in temporal brain areas, right insular cortex, and thalamus. Conclusions. Cognitive-behavioral and fMRI results support the notion that MST has significant effects in improving PWA cognitive-behavioral status by restoring neural functioning.
Background and Purpose. Patients with chronic stroke may benefit from continuing rehabilitation training after hospital discharge. This study examined whether caregiver-mediated, home-based intervention (CHI) could improve physical functioning and social participation in these patients. Methods. A single-blind, randomized, controlled 12-week trial conducted with 51 patients from 3 hospitals in Taiwan who had chronic stroke (>6 months; Brunnstrom recovery stages III-V). Patients and their caregivers in the intervention arm (n = 25) were given weekly personalized CHI trainings designed by a physical therapist. Patients in the control arm (n = 26) received visits from the therapist without intervention. All were evaluated for physical recovery through the Stroke Impact Scale, Berg Balance Scale, 10-Meter Walk Test, 6-Minute Walk Test, and Barthel Index at baseline and endpoint. Caregivers were evaluated with the Caregiver Burden Scale. Results were analyzed through Mann-Whitney U test. Results. CHI significantly improved scores of the Stroke Impact Scale: strength (control vs intervention, respectively: 1.4 vs 15.5; P = .002), mobility (–0.5 vs 13.7; P < .001), composite physical (–0.7 vs 11.2; P < .001), and general recovery domain (0.2 vs 17.4; P < .001). CHI also significantly improved free-walking velocity (–1.4 vs 7.5 cm/s; P = .006), 6-minute walk distance (–10.5 vs 15.8 m; P = .003), Berg Balance Scale score (–0.8 vs 4.5; P = .006), and Barthel Index score (0.6 vs 7.2; P = .008). CHI did not significantly increase caregiver burden at endpoint. Conclusion. CHI can improve physical functional recovery and, possibly, social participation in patients with chronic stroke.
Background. Phase III trials of rehabilitation of paresis after stroke have proven the effectiveness of intensive and extended task practice, but they have also shown that many patients do not qualify, because of severity of impairment, and that many of those who are treated are left with clinically significant deficits. Objective. To test the value of 2 potential adjuvants to normal learning processes engaged in constraint-induced movement therapy (CIMT): greater distribution of treatment over time and the coadministration of d-cycloserine, a competitive agonist at the glycine site of the N-methyl-D-aspartate glutamate receptor. Methods. A prospective randomized single-blind parallel-group trial of more versus less condensed therapy (2 vs 10 weeks) and d-cycloserine (50 mg) each treatment day versus placebo (in a 2 x 2 design), as potential adjuvants to 60 hours of CIMT. Results. Twenty-four participants entered the study, and 22 completed it and were assessed at the completion of treatment and 3 months later. Neither greater distribution of treatment nor treatment with d-cycloserine significantly augmented retention of gains achieved with CIMT. Conclusions. Greater distribution of practice and treatment with d-cycloserine do not appear to augment retention of gains achieved with CIMT. However, concentration of CIMT over 2 weeks ("massed practice") appears to confer no advantage either.
Background. Gait characteristics extracted from trunk accelerations during daily life locomotion are complementary to questionnaire- or laboratory-based gait and balance assessments and may help to improve fall risk prediction. Objective. The aim of this study was to identify gait characteristics that are associated with self-reported fall history and that can be reliably assessed based on ambulatory data collected during a single week. Methods. We analyzed 2 weeks of trunk acceleration data (DynaPort MoveMonitor, McRoberts) collected among 113 older adults (age range, 65-97 years). During episodes of locomotion, various gait characteristics were determined, including local dynamic stability, interstride variability, and several spectral features. For each characteristic, we performed a negative binomial regression analysis with the participants’ self-reported number of falls in the preceding year as outcome. Reliability of gait characteristics was assessed in terms of intraclass correlations between both measurement weeks. Results. The percentages of spectral power below 0.7 Hz along the vertical and anteroposterior axes and below 10 Hz along the mediolateral axis, as well as local dynamic stability, local dynamic stability per stride, gait smoothness, and the amplitude and slope of the dominant frequency along the vertical axis, were associated with the number of falls in the preceding year and could be reliably assessed (all P < .05, intraclass correlation > 0.75). Conclusions. Daily life gait characteristics are associated with fall history in older adults and can be reliably estimated from a week of ambulatory trunk acceleration measurements.
Background. The Microsoft Kinect presents a simple, inexpensive, and portable method of examining the independent components of the Timed Up and Go (TUG) without any intrusion on the patient. Objective. This study examined the reliability of these measures, and whether they improved prediction of performance on common clinical tests. Methods. Thirty individuals with stroke completed 4 clinical assessments, including the TUG, 10-m walk test (10MWT), Step Test, and Functional Reach test on 2 testing occasions. The TUG was assessed using the Kinect to determine 7 different functional components. Test–retest reliability was assessed using intraclass correlation coefficient (ICC), redundancy using Spearman’s correlation, and score prediction on the clinical tests using multiple regression. Results. All Kinect-TUG variables possessed excellent reliability (ICC(2,k) > 0.90) except trunk flexion angle (ICC = 0.73). Trunk flexion angle and first step length were nonredundant with total TUG time. When predicting 10MWT and Step Test scores, adding step length into regression models comprising age and total TUG time improved model performance by 7% (P <.01) and 6% (P =.03), respectively. Specifically, an interquartile range increase in first step length (0.19 m) was associated with a 0.15 m/s faster gait speed and 1.8 more repetitions on the Step Test. These effect sizes were comparable to our minimal detectable change scores of 0.17 m/s for gait speed and 1.71 repetitions for the Step Test. Conclusions. Using the Kinect to independently assess the multiple components of the TUG may provide reliable and clinically useful information. This could enable efficient and information-rich large-scale assessments of physical deficits following stroke.
Background. Previous findings suggest that language disorders may occur in severely brain-injured patients and could interfere with behavioral assessments of consciousness. However, no study investigated to what extent language impairment could affect patients’ behavioral responses. Objective. To estimate the impact of receptive and/or productive language impairments on consciousness assessment. Methods. Twenty-four acute and subacute stroke patients with different types of aphasia (global, n = 11; Broca, n = 4; Wernicke, n = 3; anomic, n = 4; mixed, n = 2) were recruited in neurology and neurosurgery units as well as in rehabilitation centers. The Coma Recovery Scale–Revised (CRS-R) was administered. Results. We observed that 25% (6 out of 24) of stroke patients with a diagnosis of aphasia and 54% (6 out of 11) of patients with a diagnosis of global aphasia did not reach the maximal CRS-R total score of 23. An underestimation of the consciousness level was observed in 3 patients with global aphasia who could have been misdiagnosed as being in a minimally conscious state, even in the absence of any documented period of coma. More precisely, lower subscores were observed on the communication, motor, oromotor, and arousal subscales. Conclusion. Consciousness assessment may be complicated by the co-occurrence of severe language deficits. This stresses the importance of developing new tools or identifying items in existing scales, which may allow the detection of language impairment in severely brain-injured patients.
Objectives. Memory training in combination with practice in semantic structuring and word fluency has been shown to improve memory performance. This study investigated the efficacy of a working memory training combined with exercises in semantic structuring and word fluency and examined whether training effects generalize to other cognitive tasks. Methods. In this double-blind randomized control study, 36 patients with memory impairments following brain damage were allocated to either the experimental or the active control condition, with both groups receiving 9 hours of therapy. The experimental group received a computer-based working memory training and exercises in word fluency and semantic structuring. The control group received the standard memory therapy provided in the rehabilitation center. Patients were tested on a neuropsychological test battery before and after therapy, resulting in composite scores for working memory; immediate, delayed, and prospective memory; word fluency; and attention. Results. The experimental group improved significantly in working memory and word fluency. The training effects also generalized to prospective memory tasks. No specific effect on episodic memory could be demonstrated. Conclusion. Combined treatment of working memory training with exercises in semantic structuring is an effective method for cognitive rehabilitation of organic memory impairment.
Background. Robotic training can help improve function of a paretic limb following a stroke, but individuals respond differently to the training. A predictor of functional gains might improve the ability to select those individuals more likely to benefit from robot-based therapy. Studies evaluating predictors of functional improvement after a robotic training are scarce. One study has found that white matter tract integrity predicts functional gains following a robotic training of the hand and wrist. Objective. To determine the predictive ability of behavioral and brain measures in order to improve selection of individuals for robotic training. Methods: Twenty subjects with chronic stroke participated in an 8-week course of robotic exoskeletal training for the arm. Before training, a clinical evaluation, functional magnetic resonance imaging (fMRI), diffusion tensor imaging, and transcranial magnetic stimulation (TMS) were each measured as predictors. Final functional gain was defined as change in the Box and Block Test (BBT). Measures significant in bivariate analysis were fed into a multivariate linear regression model. Results. Training was associated with an average gain of 6 ± 5 blocks on the BBT (P < .0001). Bivariate analysis revealed that lower baseline motor-evoked potential (MEP) amplitude on TMS, and lower laterality M1 index on fMRI each significantly correlated with greater BBT change. In the multivariate linear regression analysis, baseline MEP magnitude was the only measure that remained significant. Conclusion. Subjects with lower baseline MEP magnitude benefited the most from robotic training of the affected arm. These subjects might have reserve remaining for the training to boost corticospinal excitability, translating into functional gains.
Background. Action observation has been suggested as a possible gateway to retraining arm motor function post stroke. However, it is unclear if the neuronal response to action observation is affected by stroke and if it changes during the course of recovery. Objective. To examine longitudinal changes in neuronal activity in a group of patients with subacute stroke when observing and executing a bimanual movement task. Methods. Eighteen patients were examined twice using 3-T functional magnetic resonance imaging; 1 to 2 weeks and 3 months post stroke symptom onset. Eighteen control participants were examined once. Image time series were analyzed (SPM8) and correlated with clinical motor function scores. Results. During action observation and execution, an overlap of neuronal activation was observed in the superior and inferior parietal lobe, precentral gyrus, insula, and inferior temporal gyrus in both control participants and patients (P < .05; false discovery rate corrected). The neuronal response in the observation task increased from 1 to 2 weeks to 3 months after stroke. Most activated clusters were observed in the inferior temporal gyrus, the thalamus and movement-related areas, such as the premotor, supplementary and motor cortex (BA4, BA6). Increased activation of cerebellum and premotor area correlated with improved arm motor function. Most patients had regained full movement ability. Conclusions. Plastic changes in neurons responding to action observation and action execution occurred in accordance with clinical recovery. The involvement of motor areas when observing actions early and later after stroke may constitute a possible access to the motor system.
Background. Unilateral spatial neglect (USN) is a visual-perceptual disorder that entails the inability to perceive and integrate stimuli on one side of the body, resulting in the neglect of one side of the body. Stroke patients with USN present with extensive functional disability and duration of therapy input. Objective. To determine the effect of saccadic eye movement training with visual scanning exercises (VSEs) integrated with task-specific activities on USN poststroke. Methods. A matched-pair randomized control trial was conducted. Subjects were matched according to their functional activity level and allocated to either a control (n = 12) or an experimental group (n = 12). All patients received task-specific activities for a 4-week intervention period. The experimental group received saccadic eye movement training with VSE integrated with task specific activities as an "add on" intervention. Assessments were conducted weekly over the intervention period. Results. Statistical significant difference was noted on the King-Devick Test (P = .021), Star Cancellation Test (P = .016), and Barthel Index (P = .004). Conclusion. Intensive saccadic eye movement training with VSE integrated with task-specific activities has a significant effect on USN in patients poststroke. Results of this study are supported by findings from previously reviewed literature in the sense that the effect of saccadic eye movement training with VSE as an intervention approach has a significant effect on the visual perceptual processing of participants with USN poststroke. The significant improved visual perceptual processing translate to significantly better visual function and ability to perform activities of daily living following the stroke.
Background. Transplantation of bone marrow stromal cells (BMSCs) may contribute to functional recovery after stroke. This study was designed to clarify their mechanisms, trophic effects of neurotrophic factors, and neural differentiation. Methods. Mouse neurons exposed to glutamate were cocultured with mouse BMSCs. Either neutralizing antibodies against brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF) or Trk inhibitor K252a was added to explore the mechanism of their protective effects. Fluorescence in situ hybridization (FISH) was used to assess BDNF or NGF mRNA expression in BMSCs. The mice were subjected to permanent focal ischemia, and 7 days later, either BMSCs or the vehicle was stereotactically transplanted into the ipsilateral striatum. The mouse brains were processed for FISH and immunostaining 2 or 4 weeks after transplantation. Results. BMSCs significantly ameliorated glutamate-induced neuronal death. Treatment with anti-BDNF antibody significantly reduced their protective effects. FISH analysis showed that the majority of BMSCs expressed BDNF and NGF mRNA in vitro. BMSC transplantation significantly improved the survival of neurons in peri-infarct areas. FISH analysis revealed that approximately half of BMSCs expressed BDNF and NGF mRNA 2 weeks after transplantation; however, the percentage of BDNF and NGF mRNA-positive cells decreased thereafter. Instead, the percentage of microtubule-associated protein 2–positive BMSCs gradually increased during 4 weeks after transplantation. Conclusions. These findings strongly suggest that BDNF may be a key factor underlying the trophic effects of BMSCs. BMSCs might exhibit the trophic effect in the early stage of cell therapy and the phenotypic change toward neural cells thereafter.
Background. Although most mirror therapy studies have shown improved motor performance in stroke patients, the optimal mirror training protocol still remains unclear. Objective. To study the relative contribution of a mirror in training a reaching task and of unilateral and bimanual training with a mirror. Methods. A total of 93 stroke patients at least 6 months poststroke were instructed to perform a reaching task as fast and as fluently as possible. They performed 70 practice trials after being randomly allocated to 1 of 5 experimental groups: training with (1) the paretic arm with direct view (Paretic-No Mirror), (2) the nonparetic arm with direct view (Nonparetic-No Mirror), (3) the nonparetic arm with mirror reflection (Nonparetic Mirror), (4) both sides and with a nontransparent screen preventing visual control of paretic side (Bilateral-Screen), and (5) both sides with mirror reflection of the nonparetic arm (Bilateral-Mirror). As baseline and follow-up, patients performed 6 trials using only their paretic side. Primary outcome measure was the movement time. Results. We found the largest intervention effect in the Paretic-No Mirror condition. However, the Nonparetic-Mirror condition was not significantly different from the Paretic-No Mirror condition, while the Unaffected-No Mirror condition had significantly less improvement than the Paretic-No Mirror condition. In addition, movement time improved significantly less in the bimanual conditions and there was no difference between both bimanual conditions or between both mirror conditions. Conclusion. The present study confirms that using a mirror reflection can facilitate motor learning. In this task, bimanual movement using mirror training was less effective than unilateral training.
Background. Rehabilitation after severe stroke is often limited because of impairments in sensorimotor function. Functional and physiological recovery after severe stroke is poorly understood and has not been studied extensively. Objective. This study’s purpose was to examine functional and physiological recovery of standing balance during inpatient rehabilitation in people with severe impairments after stroke. Methods. A total of 10 participants with severe impairments after stroke were evaluated monthly in a stroke rehabilitation unit with the following functional outcome measures: Berg Balance Scale (BBS), Clinical Outcome Variables Scale (COVS), and Chedoke McMaster Stroke Assessment (CMSA). Weight bearing (WB), center of pressure (COP) velocity, and electromyography (EMG) data were collected during quiet standing and during internal perturbation with a rapid nonparetic arm raise. Results. Cross-sectionally, there were moderate to strong correlations for EMG area and WB with CMSA and COVS. Additionally, the BBS was correlated with WB on the paretic side. Longitudinally, statistically significant improvement was found for functional measures but not for physiological measures. The mean BBS and COVS improved by 23 and 21 points, respectively. COP velocity decreased by 60.1% on the paretic leg but not significantly. Conclusions. During stroke rehabilitation, all participants improved functionally. Some patients improved physiologically, though near discharge, all participants remained very impaired. Future studies with larger sample sizes are needed to explore the capacity for physiological recovery in this population.
Background. Previous research using the streamlined Wolf Motor Function Test (SWMFT) has focused either on the 3- to 9-month period or on the >12-month period after stroke and lacked the information for those at 9 to 12 months. Whether SWMFT scores reflect motor deficit and recovery from early to late stages after stroke remains unclear. Objective. A retrospective study using the Functional Ability Scale (FAS) was conducted to evaluate whether all SWMFTs items measure the poststroke recovery of upper extremity (UE) motor function and if they could be used for patients within 9 to 12 months after a stroke. Methods. Rasch analysis was conducted, and data were drawn from patients 3 months to years after a stroke. Results. The continuum of UE motor function in SWMFT-FAS was supported. Subacute patients had the best motor function, followed by the 9- to 12-month group, and then chronic patients. Variation in UE motor function was large (2.35-2.72 logits), and motor abilities of these 3 groups overlapped. The 8 SWMFT items could target a broad range of UE motor function, from –8.28 to 7.80 logits. The average difficulty of these 8 items also matched the UE motor ability of the subgroup at 9 to 12 months after stroke, and individual versions of the SWMFT performed well to assess the motor ability of this group. Conclusions. The SWMFTs had sound hierarchical properties. The SWMFT-Chronic or the SWMFT-Subacute could be used to evaluate UE function of this subgroup at 9 to 12 months after stroke.
Background. Neurological deficits after a stroke are commonly classified according to motor function for clinical decision making regarding discharge and rehabilitation. Participants in clinical stroke studies are also stratified by motor function to avoid a sampling bias. Objective. This post hoc analysis examined a suite of upper limb functional assessment tools to test the hypothesis that motor function of survivors of stroke can be stratified using 2 simple tests of manual dexterity despite the heterogeneity of the population. Methods. The functional ability of the more affected hand and arm was assessed for 67 hemiparetic patients, aged 18 to 83 years (mean ± standard deviation, 59.8 ± 14.0 years), at 1 to 264 months after a stroke (23.6 ± 39.6 months) using the Wolf Motor Function Test (WMFT), upper limb motor Fugl-Meyer Assessment (F-M), Box and Block Test (BBT), grooved pegboard test, and wrist range of motion. We tested the strength of our proposed stratification scheme with a hypothesis-driven hierarchical cluster analysis using standardized raw scores and dichotomous BBT and grooved pegboard test values. Results. The most salient discriminator between low and higher motor function was the ability to move >1 block on the BBT. Within the higher function group, the ability to place all 25 pegs on the grooved pegboard test discriminated between moderate and high motor function. The derived scheme was congruent with clinical observations. The WMFT timed tasks, F-M scores, and range of motion did not discriminate functional groups. Conclusions. Two simple unambiguous and objective tests of gross (BBT) and fine (grooved pegboard test) manual dexterity discriminated 3 groups of motor function ability for a heterogeneous group of patients after stroke.
Background. Motor deficits after a stroke are thought to be compounded by the development of asymmetric interhemispheric inhibition. Bilateral priming was developed to rebalance this asymmetry and thus improve therapy efficacy. Objective. This study investigated the effect of bilateral priming before Wii-based Movement Therapy to improve rehabilitation after stroke. Methods. Ten patients who had suffered a stroke (age, 23-77 years; 3-123 months after stroke) underwent a 14-day program of Wii-based Movement Therapy for upper limb rehabilitation. Formal Wii-based Movement Therapy sessions were immediately preceded by 15 minutes of bilateral priming, whereby active flexion-extension of the less affected wrist drove mirror-symmetric passive movements of the more affected wrist through a custom device. Functional movement was assessed at weeks 0 (before therapy), 3 (after therapy), and 28 (follow-up) using the Wolf Motor Function Test (WMFT), upper limb Fugl-Meyer Assessment (FMA), upper limb range of motion, and Motor Activity Log (MAL). Case-matched controls were patients who had suffered a stroke who received Wii-based Movement Therapy but not bilateral priming. Results. Upper limb functional ability improved for both groups on all measures tested. Posttherapy improvement on the FMA for primed patients was twice that of the unprimed patients (37.3% vs 14.6%, respectively) and was significantly better maintained at 28 weeks (P = .02). Improvements on the WMFT and MAL were similar for both groups, but the pattern of change in range of motion was strikingly different. Conclusions. Bilateral priming before Wii-based Movement Therapy led to a greater magnitude and retention of improvement compared to control, especially measured with the FMA. These data suggest that bilateral priming can enhance the efficacy of Wii-based Movement Therapy, particularly for patients with low motor function after a stroke.
Objective. The aim of this study was to assess whether the combination of Adapted Physical Activity (APA) and Therapeutic Patient Education (TPE) improves function and quality of life in survivors of strokes. Methods. This nonrandomized controlled study enrolled patients with mild to moderate hemiparesis referred to 2 physical medicine and rehabilitation units in Emilia-Romagna, Italy, 3 to 18 months after a single unilateral mild to moderate stroke. The experimental group (n = 126) received 16 APA sessions and 3 sessions of TPE, and the control group (n = 103) received usual care; 86.9% completed treatment. The main outcome measure was a 4-month change in gait endurance (that corresponds to 2 months after intervention in the experimental group), and secondary outcomes included the Short Physical Performance Battery, Berg Balance Scale, Barthel Index, Geriatric Depression Scale, 12-item Short-Form Health Survey, and Caregiver Strain Index. Changes in scores at 4 months were compared between groups using analysis of variance and controlling for group imbalance by means of the propensity score. Results. Gait endurance, physical performance, balance, and the physical component of the quality of life score increased significantly at 4 months in the APA group and remained stable in the control group. The propensity-adjusted between-group change was significant for these scores at P < .01. Conclusions. Our results confirm that it is feasible and potentially effective to implement APA programs for elderly patients with complex clinical conditions as early as 3 months after a stroke and suggest that, when combined with TPE, the effects of a postrehabilitation APA program are relatively enduring.
Background. A quadratic formula of the Spinal Cord Injury Ability Realization Measurement Index (SCI-ARMI) has previously been published. This formula was based on a model of Spinal Cord Independence Measure (SCIM95), the 95th percentile of the SCIM III values, which correspond with the American Spinal Injury Association Motor Scores (AMS) of SCI patients. Objective. To further develop the original formula. Setting. Spinal cord injury centers from 6 countries and the Statistical Laboratory, Tel-Aviv University, Israel. Methods. SCIM95 of 661 SCI patients was modeled, using a quantile regression with or without adjustment for age and gender, to calculate SCI-ARMI values. SCI-ARMI gain during rehabilitation and its correlations were examined. Results. A new quadratic SCIM95 model was created. This resembled the previously published model, which yielded similar SCIM95 values in all the countries, after adjustment for age and gender. Without this adjustment, however, only 86% of the non-Israeli SCIM III observations were lower than those SCIM95 values (P < .0001). Adding the variables age and gender to the new model affected the SCIM95 value significantly (P < .04). Adding country information did not add a significant effect (P > .1). SCI-ARMI gain was positive (38.8 ± 22 points, P < .0001) and correlated weakly with admission age and AMS. Conclusions. The original quadratic SCI-ARMI formula is valid for an international population after adjustment for age and gender. The new formula considers more factors that affect functional ability following SCI.
Background. Creating the visual illusion of touch can improve tactile perception in healthy subjects. Objective. We were interested in seeing if creating the illusion of touch in an insensate area could improve sensation in that area. Methods. Fourteen people with chronic numbness participated in a randomized crossover experiment. The 4 conditions were the following: (a) stimulation over the unaffected limb with mirror visual feedback (experimental condition), (b) stimulation over the affected limb with mirror visual feedback, (c) stimulation over the unaffected limb without mirror visual feedback, and (d) stimulation over the affected limb without mirror visual feedback. Participants were assessed before and after each condition using the Ten-Test and mechanical detection thresholds. Data were analyzed using linear mixed models. Result. Only the experimental condition produced a change in the Ten-Test (mean difference = –1.1; 95% confidence interval = –1.8 to –0.4; P = .003), corresponding to a 24% improvement in sensation. No differences were observed for any condition in mechanical detection thresholds. Conclusion. Creating the illusion of touch may improve sensory function in areas of chronic numbness. This preliminary finding adds to the growing body of evidence supporting the use of techniques that directly target cortical function in people with peripheral nerve injury.
Background. There is inherent heterogeneity within individuals suffering from cervical spinal cord injury (SCI), and early prediction of upper limb function and self-care is challenging. As a result, considerable uncertainty exists regarding the prediction of functional outcome following cervical SCI within 1 year of injury. Objective. To evaluate the value of Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) in predicting upper limb function and self-care outcomes in individuals with cervical SCI. Method. A prospective longitudinal multicenter study was performed. Data from the GRASSP, the Spinal Cord Independence Measure (SCIM III), and the American Spinal Injury Association (ASIA) Impairment Scale were recorded at 1, 6, and 12 months after cervical SCI. For prediction of functional outcome at 6 and 12 months, a logistic regression model, receiver operating characteristics (ROC), and unbiased recursive partitioning conditional inference tree (URP-CTREE) were used with 8 different predictor variables. Results. Logistic regression analysis, ROC analysis, and URP-CTREE all revealed that the strength subtest within GRASSP is the strongest predictor for upper limb function and self-care outcomes. URP-CTREE provides useful information on the distribution of different outcomes in acute cervical SCI and can be used to predict cohorts with homogeneous outcomes. Conclusion. The GRASSP at 1 month can accurately predict upper limb function and self-care outcomes even in a heterogeneous group of individuals across a wide spectrum of neurological recovery. The application of URP-CTREE can reveal the distribution of outcome categories and, based on this, inform trial protocols with respect to outcomes analysis and patient stratification.
Background. Recent work has shown that resting-state functional connectivity (rsFC) between homotopic, motor-related brain regions is associated with upper-extremity control early after stroke. Objectives. This study examined various patterns of rsFC in chronic stroke, a time at which extensive neural reorganization has occurred. Associations between homotopic somatomotor connectivity and clinical measures, representing separate domains of upper-extremity function, were determined. Methods. A total of 19 persons ≥6 months poststroke participated. Four connectivity patterns within a somatomotor network were quantified using functional magnetic resonance imaging. Upper-extremity gross muscle activation, control, and real-world use were evaluated with the Motricity Index, Action Research Arm Test, and accelerometry, respectively. Results. Connectivity between homotopic regions was stronger than that in the contralesional and ipsilesional hemispheres. No differences in connectivity strength were noted between homotopic pairs, indicating that a specific brain structure was not driving somatomotor network connectivity. Homotopic connectivity was significantly associated with both upper-extremity control (r = 0.53; P= .02) and real-world use (r = 0.54; P= .02); however, there was no association with gross muscle activation (r = 0.23; P=.34). The combination of clinical measures accounted for 40% of the variance in rsFC (= .05). Conclusions. The results reported here expand on previous findings, indicating that homotopic rsFC persists in chronic stroke and discriminates between varying levels of upper-extremity control and real-world use. Further work is needed to evaluate its adequacy as a biomarker of motor recovery following stroke.
Background. Regular exercise reduces the risk of a first-ever stroke and is associated with smaller infarcts. Although evidence has suggested that therapeutic exercise following stroke is beneficial, we do not yet know whether exercise reduces stroke severity and improves functional recovery. The mechanisms underlying any benefit remain unclear. Objective. To conduct a systematic review and meta-analysis of studies testing exercise in animal models of ischemic stroke where outcomes were measured as infarct volume, neurobehavioral score, neurogenesis, or a combination of these. We also sought evidence of publication bias. Methods. We searched 3 online databases for publications reporting the use of exercise in focal cerebral ischemia. We used DerSimonian and Laird normalized random-effects meta-analysis and meta-regression to determine the impact of study quality and design on the efficacy of exercise. Results. Overall, exercise reduced infarct volume by 25.2% (95% confidence interval [CI] = 19.0%-31.3%; 65 experiments and 986 animals) and improved neurobehavioral score by 38.2% (95% CI = 29.1%-47.3%; 42 experiments; n = 771). For both outcomes, larger effects were seen when exercise preceded ischemia rather than came after it. For neurobehavioral scores, we found evidence of publication bias. Reported study quality was moderate (median score 5/10). Both model-specific (eg, type of ischemia) and exercise-specific characteristics influenced reported outcome. Conclusion. Exercise, either before or after ischemia, reduced infarct volume and improved neurobehavioral score. However, overall estimates of efficacy were higher in studies at risk of bias, and for neurobehavioral outcomes, there was evidence of a substantial publication bias.
Neural plasticity is widely believed to support functional recovery following brain damage. Vagus nerve stimulation paired with different forelimb movements causes long-lasting map plasticity in rat primary motor cortex that is specific to the paired movement. We tested the hypothesis that repeatedly pairing vagus nerve stimulation with upper forelimb movements would improve recovery of motor function in a rat model of stroke. Rats were separated into 3 groups: vagus nerve stimulation during rehabilitation (rehab), vagus nerve stimulation after rehab, and rehab alone. Animals underwent 4 training stages: shaping (motor skill learning), prelesion training, postlesion training, and therapeutic training. Rats were given a unilateral ischemic lesion within motor cortex and implanted with a left vagus nerve cuff. Animals were allowed 1 week of recovery before postlesion baseline training. During the therapeutic training stage, rats received vagus nerve stimulation paired with each successful trial. All 17 trained rats demonstrated significant contralateral forelimb impairment when performing a bradykinesia assessment task. Forelimb function was recovered completely to prelesion levels when vagus nerve stimulation was delivered during rehab training. Alternatively, intensive rehab training alone (without stimulation) failed to restore function to prelesion levels. Delivering the same amount of stimulation after rehab training did not yield improvements compared with rehab alone. These results demonstrate that vagus nerve stimulation repeatedly paired with successful forelimb movements can improve recovery after motor cortex ischemia and may be a viable option for stroke rehabilitation.
Background. Physical therapy intervention is the primary treatment for gait ataxia and imbalance in individuals with cerebellar damage. Our aim was to determine if a home balance exercise program is feasible for improving locomotor and balance abilities in these individuals. Methods. A total of 14 patients with cerebellar ataxia participated in a 6-week individualized home-based balance exercise program and attended 5 testing sessions (2 pretraining, 1 midtraining, 1 posttraining, and 1 one-month follow-up visit). Pretraining, posttraining, and follow-up testing included a neurological assessment, clinical gait and balance tests, and laboratory assessments of balance and walking. Participants kept logs of the frequency and level of balance challenge during their training. Results. Walking speed improved across visits, as did stride length, percentage double-limb support time, Timed Up and Go (TUG), and Dynamic Gait Index. Post hoc comparisons in these measures revealed that significant rehabilitative improvements occurred over the 6-week training period, and all but TUG gains were retained 1 month later. There were no changes across the other measures for the group. Regression analysis indicated that improvements in walking speed were affected by the level of balance challenge but not by age, ataxia severity, proprioception, or duration of exercise. Conclusions. Improvement in locomotor performance in people with cerebellar ataxia was observable after a 6-week home balance exercise program. The exercise program must be designed to provide a significant challenge to the person’s balance.
Background. While prior preliminary studies have broadened our understanding of how repetitive transcranial magnetic stimulation (rTMS) improves language outcomes in stroke patients with nonfluent aphasia, the evidence base of the effectiveness of this method remains inadequate. Objective. In this study, we aimed to strengthen the evidence that this approach improves language performance and to identify characteristics of patients predisposed to benefit most from this treatment. Methods. Fifty-six stroke patients with nonfluent aphasia were randomly allocated to a real or a sham stimulation group: Group A (n = 33), who underwent 10 sessions of 1-Hz rTMS over the contralesional pars triangularis (PTr), and Group B (n = 23), who received sham 1-Hz stimulation. We performed the Picture Naming Test and the Concise Chinese Aphasia Test (CCAT) at the baseline, post-rTMS intervention, and at 3-month follow-up. Results. Group A showed significantly greater improvement than Group B in CCAT scoring (P < .001), object-naming accuracy (P = .01), and naming reaction time (P = .004). The CCAT scoring and naming testing changes for Group A were persistent at 3 months following intervention (P = .008). Patients who had a lower contralesional rest motor threshold (rMT) were predisposed to a favorable therapeutic outcome (P = .006), independent of aphasia type, severity, and duration. Conclusions. The results of this study provide evidence that inhibitory rTMS, through downregulating the circuitry of the right pars triangularis (PTr), achieves a persistent and broadly modulating effect, irrespective of aphasia severity and subtype. Patients who show lower rMT in the right motor system would seem to benefit the most from inhibitory rTMS.
Background. Evidence supports peroneal nerve functional electrical stimulation (FES) as an effective alternative to ankle-foot orthoses (AFO) for treatment of foot drop poststroke, but few randomized controlled comparisons exist. Objective. To compare changes in gait and quality of life (QoL) between FES and an AFO in individuals with foot drop poststroke. Methods. In a multicenter randomized controlled trial (ClinicalTrials.gov #NCT01087957) with unblinded outcome assessments, 495 Medicare-eligible individuals at least 6 months poststroke wore FES or an AFO for 6 months. Primary endpoints: 10-Meter Walk Test (10MWT), a composite of the Mobility, Activities of Daily Living/Instrumental Activities of Daily Living, and Social Participation subscores on the Stroke Impact Scale (SIS), and device-related serious adverse event rate. Secondary endpoints: 6-Minute Walk Test, GaitRite Functional Ambulation Profile (FAP), Modified Emory Functional Ambulation Profile (mEFAP), Berg Balance Scale (BBS), Timed Up and Go, individual SIS domains, and Stroke-Specific Quality of Life measures. Multiply imputed intention-to-treat analyses were used with primary endpoints tested for noninferiority and secondary endpoints tested for superiority. Results. A total of 399 subjects completed the study. FES proved noninferior to the AFO for all primary endpoints. Both the FES and AFO groups improved significantly on the 10MWT. Within the FES group, significant improvements were found for SIS composite score, total mFEAP score, individual Floor and Obstacle course time scores of the mEFAP, FAP, and BBS, but again, no between-group differences were found. Conclusions. Use of FES is equivalent to the AFO. Further studies should examine whether FES enables better performance in tasks involving functional mobility, activities of daily living, and balance.
Background. Prognosis of long-term motor outcome of acute stroke patients with severe motor impairment is difficult to determine. Objective. Our primary goal was to evaluate the prognostic value of corticospinal tract (CST) injury on motor outcome of the upper limb compared with motor impairment level and lesion volume. Methods. In all, 10 acute stroke patients with moderately severe to severe motor impairment of the upper limb underwent diffusion tensor imaging (DTI) and testing of upper limb strength and dexterity at acute, subacute, and chronic poststroke time points. A density-weighted CST atlas was constructed using DTI tractography data from normal participants. This CST atlas was applied, using a largely automated process, to DTI data from patients to quantify CST injury at each time point. Differences in axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) of the ipsilesional CST relative to the contralesional CST were measured. Results. Acute loss in CST AD correlated most strongly and significantly with subacute and chronic strength and dexterity and remained significant after adjusting for acute motor impairment or lesion volume. Subacute loss in CST FA correlated most strongly with chronic dexterity, whereas subacute behavioral measures of limb strength correlated most strongly with chronic strength measures. Conclusions. Loss in acute CST AD and subacute CST FA are strong prognostic indicators of future motor functions of the upper limb for stroke patients with substantial initial motor impairment. DTI-derived measure of CST injury early after stroke may have utility in health care planning and in design of acute stroke clinical trials.
Background. Previous research has shown that during simulated activities of daily living, right-handed stroke patients use their contralesional arm more after left- than right-hemisphere stroke. These findings were attributed to a hand preference effect. However, these decisions about when to use the contralesional arm may be modulated by where in the work space the task is performed, a factor that could be used in physical rehabilitation to influence recovery by decreasing learned nonuse. Objective. To examine how target location and side of stroke influences arm selection choices for simple reaching movements. Methods. A total of 14 right-handed stroke patients (7 with left-hemisphere and 7 with right-hemisphere damage [RHD]), with similar degrees of hemiparesis (Fugl-Meyer motor score), and 16 right-handed controls participated in this experiment. In a pseudorandom fashion, 32 targets were presented throughout the reachable horizontal plane work space, and the participants were asked to select 1 hand to reach the target on each trial. Results. The group with left-hemisphere damage chose their contralesional arm significantly more often than the group with RHD. Patients with RHD also chose their left (contralesional) arm significantly less often than the control group. However, these patterns of choice were most pronounced in the center of the workspace. Conclusion. Both the side of hemisphere damage and work space location played a significant role in the choice of whether to use the contralesional arm for reaching. These findings have implications for structuring rehabilitation for unilateral stroke patients.
Functional recovery following central nervous system injuries is strongly influenced by rehabilitative training. In the clinical setting, the intensity of training and the level of motivation for a particular task are known to play important roles. With increasing neuroscience studies investigating the effects of training and rehabilitation, it is important to understand how the amount and type of training of individuals influences outcome. However, little is known about the influence of spontaneous "self-training" during daily life as it is often uncontrolled, not recorded, and mostly disregarded. Here, we investigated the effects of the intensity of self-training on motor skill acquisition in normal, intact rats and on the recovery of functional motor behavior following spinal cord injury in adult rats. We used a custom-designed small animal tracking system, "RatTrack," to continuously record the activity of multiple rats, simultaneously in a complex Natural Habitat–enriched environment. Naïve, adult rats performed high-intensity, self-motivated motor training, which resulted in them out-performing rats that were conventionally housed and trained on skilled movement tasks, for example, skilled prehension (grasping) and ladder walking. Following spinal cord injury the amount of self-training was correlated with improved functional recovery. These data suggest that high-impact, self-motivated training leads to superior skill acquisition and functional recovery than conventional training paradigms. These findings have important implications for the design of animal studies investigating rehabilitation and for the planning of human rehabilitation programs.
Background. Many stroke patients exhibit excessive compensatory trunk movements during reaching. Compensatory movement behaviors may improve upper extremity function in the short-term but be detrimental to long-term recovery. Objective. To evaluate the evidence that trunk restraint limits compensatory trunk movement and/or promotes better upper extremity recovery in stroke patients. Methods. A search was conducted through electronic databases from January 1980 to June 2013. Only randomized controlled trials (RCTs) comparing upper extremity training with and without trunk restraint were selected for review. Three review authors independently assessed the methodological quality and extracted data from the studies. Meta-analysis was conducted when there was sufficient homogenous data. Results. Six RCTs involving 187 chronic stroke patients were identified. Meta-analysis of key outcome measures showed that trunk restraint has a moderate statistically significant effect on improving Fugl-Meyer Upper Extremity (FMA-UE) score, active shoulder flexion, and reduction in trunk displacement during reaching. There was a small, nonsignificant effect of trunk restraint on upper extremity function. Conclusion. Trunk restraint has a moderate effect on reduction of upper extremity impairment in chronic stroke patients, in terms of FMA-UE score, increased shoulder flexion, and reduction in excessive trunk movement during reaching. There is insufficient evidence to demonstrate that trunk restraint improves upper extremity function and reaching trajectory smoothness and straightness in chronic stroke patients. Future research on stroke patients at different phases of recovery and with different levels of upper extremity impairment is recommended.
Background. Arm paresis remains a major impairment after stroke despite the best conventional rehabilitation. Randomized, controlled trials of intensive exercise programs have demonstrated improvements in arm function for patients with chronic stroke. However, the gains achieved have been relatively modest for the large investments in patient and therapist time. Objective. To evaluate the safety, acceptance, adherence, and effectiveness of a community-based exercise program for upper limb paresis in patients with chronic stroke and the effects of telerehabilitation monitoring in kiosks distributed through the community. Methods. Longitudinal cohort with geographic control group. The experimental group received devices needed for a home exercise program based on the Carr and Shepherd "Motor Learning Program" and were instructed to practice the exercises at least twice a week at the kiosk and at least 3 more days a week at home. The control group received usual care. Results. Compared with the control group, patients in the experimental group demonstrated significant gains in arm function as measured by the Wolf Motor Function Test, 9-Hole Peg Test, Motricity Index, and Nottingham Extended Activities of Daily Living Questionnaire. The intervention received high satisfaction ratings and produced no adverse events. Only 30% of the subjects attended kiosks regularly. Outcomes for this group did not differ significantly from those who only practiced at home. Conclusions. Home- and community-based exercise for arm paresis is safe and effective. Telerehabilitation interventions will need additional enhancements to improve effectiveness. The optimal upper extremity exercise prescription poststroke remains to be established.
Background. Video games have become popular in stroke rehabilitation; however, the nature of this intervention is not fully understood. Objectives. To compare the number of (a) purposeful and nonpurposeful repetitions of the weaker upper extremity (UE) and (b) movement accelerations as assessed by accelerometer activity counts of the weaker and stronger UEs of individuals with chronic stroke while playing video games or participating in traditional therapy. Methods. Twenty-nine individuals (mean age 59 years, 1-7 years poststroke) took part in a group intervention of video -games (n = 15) or traditional therapy (n = 14) as part of a randomized controlled trial. During 1 - 2 sessions, participants were video-taped while wearing wrist accelerometers. Assessors counted the number of repetitions and classified movements as purposeful or nonpurposeful using videotapes. The weaker UE motor impairments were correlated to movement accelerations, to determine if participants were using their potential during the sessions. Results. Participants in the video game group performed a median of 271 purposeful movements and 37 970 activity counts compared to 48 purposeful movements and 14 872 activity counts in the traditional group (z = –3.0, P = .001 and z = –1.9, P = .05, respectively). Participants in the traditional group performed a median of 26 nonpurposeful (exercises) compared with 0 in the video game group (z = –4.2, P = .000). Strong significant correlations were found between the motor ability of the weak UE to repetitions of participants in both groups (r = .86, P < .01). Participants with higher motor ability performed more repetitions. Conclusions. Video games elicited more UE purposeful repetitions and higher acceleration of movement compared with traditional therapy in individuals with chronic stroke.
Resting state functional connectivity magnetic resonance imaging studies in rat brain show brain reorganization caused by nerve injury and repair. In this study, distinguishable differences were found in healthy, nerve transection without repair (R–) and nerve transection with repair (R+) groups in the subacute stage (2 weeks after initial injury). Only forepaw on the healthy side was used to determine seed voxel regions in this study. Disturbance of neuronal network in the primary sensory region of cortex occurs within two hours after initial injury, and the network pattern was restored in R+ group in subacute stage, while the disturbed pattern remained in R– group. These are the central findings of the study. This technique provides a novel way of detecting and monitoring the effectiveness of peripheral nerve injury treatment in the early stage and potentially offers a tool for clinicians to avoid poor clinical outcomes.
Background. Previous data suggest that the amount and aerobic intensity of stepping training may improve walking poststroke. Recent animal and human studies suggest that training in challenging and variable contexts can also improve locomotor function. Such practice may elicit substantial stepping errors, although alterations in locomotor strategies to correct these errors could lead to improved walking ability. Objective. This unblinded pilot study was designed to evaluate the feasibility and preliminary efficacy of providing stepping practice in variable, challenging contexts (tasks and environments) at high aerobic intensities in participants >6 months and 1-6 months post-stroke. Methods. A total of 25 participants (gait speeds <0.9 m/s with no more than moderate assistance) participated in ≤40 training sessions (duration of 1 hour) within 10 weeks. Stepping training in variable, challenging contexts was performed at 70% to 80% heart rate reserve, with feasibility measures of total steps/session, ability to achieve targeted intensities, patient tolerance, dropouts, and adverse events. Gait speed, symmetry, and 6-minute walk were measured every 4 to 5 weeks or 20 sessions, with a 3-month follow-up (F/U). Results. In all, 22 participants completed ≥4 training weeks, averaging 2887 ± 780 steps/session over 36 ± 5.8 sessions. Self-selected (0.38 ± 0.27 to 0.66 ± 0.35 m/s) and fastest speed (0.51 ± 0.40 to 0.99 ± 0.58 m/s), paretic single-limb stance (20% ± 5.9% to 25% ± 6.4%), and 6-minute walk (141 ± 99 to 260 ± 146 m) improved significantly at posttraining. Conclusions. This preliminary study suggests that stepping training at high aerobic intensities in variable contexts was tolerated by participants poststroke, with significant locomotor improvements. Future studies should delineate the relative contributions of amount, intensity, and variability of stepping training to maximize outcomes.
Background. Modular lower extremity robotics may offer a valuable avenue for restoring neuromotor control after hemiparetic stroke. Prior studies show that visually guided and visually evoked practice with an ankle robot (anklebot) improves paretic ankle motor control that translates into improved overground walking. Objective. To assess the feasibility and efficacy of daily anklebot training during early subacute hospitalization poststroke. Methods. Thirty-four inpatients from a stroke unit were randomly assigned to anklebot (n = 18) or passive manual stretching (n = 16) treatments. All suffered a first stroke with residual hemiparesis (ankle manual muscle test grade 1/5 to 4/5), and at least trace muscle activation in plantar- or dorsiflexion. Anklebot training employed an "assist-as-needed" approach during >200 volitional targeted paretic ankle movements, with difficulty adjusted to active range of motion and success rate. Stretching included >200 daily mobilizations in these same ranges. All sessions lasted 1 hour and assessments were not blinded. Results. Both groups walked faster at discharge; however, the robot group improved more in percentage change of temporal symmetry (P = .032) and also of step length symmetry (P = .038), with longer nonparetic step lengths in the robot (133%) versus stretching (31%) groups. Paretic ankle control improved in the robot group, with increased peak (P ≤ .001) and mean (P ≤ .01) angular speeds, and increased movement smoothness (P ≤ .01). There were no adverse events. Conclusion. Though limited by small sample size and restricted entry criteria, our findings suggest that modular lower extremity robotics during early subacute hospitalization is well tolerated and improves ankle motor control and gait patterning.
Background. Reduced physical activity is an important consequence of multiple sclerosis (MS). However, little is known about the real quantity and type of daily activities that people with MS perform in their own home environment. Objective. To gain insight into differences in the amount and patterns of physical activities performed over a 24-hour period in the own community environment of patients with MS and healthy individuals. Methods. A total of 43 ambulatory patients with MS and 26 age- and gender-matched healthy individuals participated. Physical activity recorded with an ambulatory activity monitor was classified into postures and motions. Multilevel analyses were conducted to investigate whether the pattern of physical activities across daily periods (morning, afternoon, and evening) was dependent on the group (MS vs healthy individuals). Results. Results showed a significant overall lower amount of dynamic activity as compared with a group of healthy controls (P < .001). Patients with MS started with lower physical activity levels already in the morning (P < .001), and this difference persisted in the afternoon (P = .002) and evening (P = .032). Conclusion. Activity monitoring gives insight into real-world daily physical behavior. Our findings suggest that patients with MS may adopt a deliberate anticipatory strategy of lower activity in the morning, which persists throughout the day. Future trials evaluating daily changes in physical activity behavior should simultaneously sample self-report measures of energy levels and fatigue to elucidate the complex interaction between symptoms and physical activity.
Background. Recent neuroimaging studies on poststroke aphasia revealed maladaptive cortical changes in both hemispheres, yet their functional contribution in language recovery remains elusive. The aim of this study was to evaluate the long-term efficacy of dual-hemisphere repetitive transcranial magnetic stimulation (rTMS) on poststroke aphasia. Methods. Thirty patients with subacute poststroke nonfluent aphasia were randomly allocated to receive real or sham rTMS. Each patient received 1000 rTMS pulses (1 Hz at 110% of resting motor threshold [rMT] over the right unaffected Broca’s area and 1000 pulses (20 Hz at 80% rMT) over the left affected Broca’s area for 10 consecutive days followed by speech/language training. The language section of the Hemispheric Stroke Scale (HSS), the Stroke Aphasic Depression Questionnaire–Hospital Version (SADQ-H), and the National Institutes of Health Stroke Scale (NIHSS) were measured before, immediately after the 10 sessions, and 1 and 2 months after the last session. Results. At baseline, there were no significant differences between groups in demographic and clinical rating scales. However, there was a significantly greater improvement in the HSS language score as well as in the SADQ-H after real rTMS compared with sham rTMS, which remained significant 2 months after the end of the treatment sessions. Conclusion. This is the first clinical study of dual-hemisphere rTMS in poststroke aphasia. Combining dual-hemisphere rTMS with language training might be a feasible treatment for nonfluent aphasia; further multicenter studies are needed to confirm this result.
Background. Evaluation of treatment effects on walking requires appropriate and responsive outcome measures. Objectives. To determine responsiveness of 5 walking measures and provide reference values for clinically meaningful improvements, according to disability level, in persons with multiple sclerosis (pwMS). Methods. Walking tests were measured pre- and postrehabilitation in 290 pwMS from 17 European centers. Combined anchor- and distribution-based methods determined responsiveness of objective short and long walking capacity tests (Timed 25-Foot Walk [T25FW] and 2- and 6-Minute Walk Tests [2MWT and 6MWT] and of the patient-reported Multiple Sclerosis Walking Scale–12 [MSWS-12]). A global rating of change scale, from patients’ and therapists’ perspective, was used as external criteria to determine the area under the receiver operating characteristic curve (AUC), minimally important change (MIC), and smallest real change (SRC). Patients were stratified into disability subgroups (Expanded Disability Status Scale score ≤4 [n = 98], >4 [n = 186]). Results. MSWS-12, 2MWT, and 6MWT were more responsive (AUC 0.64-0.73) than T25FW (0.50-0.63), especially in moderate to severely disabled pwMS. Clinically meaningful changes (MICs) from patient and therapist perspective were –10.4 and –11.4 for MSWS-12 (P < .01), 9.6 m and 6.8 m for 2MWT (P < .05), and 21.6 m (P < .05) and 9.1 m (P = .3) for 6MWT. In subgroups, MIC was significant from patient perspective for 2MWT (10.8 m) and from therapist perspective for MSWS-12 (–10.7) in mildly disabled pwMS. In moderate to severely disabled pwMS, MIC was significant for MSWS-12 (–14.1 and –11.9). Conclusions. Long walking tests and patient-reported MSWS-12 were more appropriate than short walking tests in detecting clinically meaningful improvement after physical rehabilitation, particularly the MSWS-12 for moderate to severely disabled pwMS.
Background. Thus far, most of the brain–computer interfaces (BCIs) developed for motor rehabilitation used electroencephalographic signals to drive prostheses that support upper limb movement. Only few BCIs used hemodynamic signals or were designed to control lower extremity prostheses. Recent technological developments indicate that functional near-infrared spectroscopy (fNIRS)-BCI can be exploited in rehabilitation of lower limb movement due to its great usability and reduced sensitivity to head motion artifacts. Objective. The aim of this proof of concept study was to assess whether hemodynamic signals underlying lower limb motor preparation in stroke patients can be reliably measured and classified. Methods. fNIRS data were acquired during preparation of left and right hip movement in 7 chronic stroke patients. Results. Single-trial analysis indicated that specific hemodynamic changes associated with left and right hip movement preparation can be measured with fNIRS. Linear discriminant analysis classification of totHB signal changes in the premotor cortex and/or posterior parietal cortex indicated above chance accuracy in discriminating paretic from nonparetic movement preparation trials in most of the tested patients. Conclusion. The results provide first evidence that fNIRS can detect brain activity associated with single-trial lower limb motor preparation in stroke patients. These findings encourage further investigation of fNIRS suitability for BCI applications in rehabilitation of patients with lower limb motor impairment after stroke.
Background. The reliable stratification of homogeneous subgroups and the prediction of future clinical outcomes within heterogeneous neurological disorders is a particularly challenging task. Nonetheless, it is essential for the implementation of targeted care and effective therapeutic interventions. Objective. This study was designed to assess the value of a recently developed regression tool from the family of unbiased recursive partitioning methods in comparison to established statistical approaches (eg, linear and logistic regression) for predicting clinical endpoints and for prospective patients’ stratification for clinical trials. Methods. A retrospective, longitudinal analysis of prospectively collected neurological data from the European Multicenter study about Spinal Cord Injury (EMSCI) network was undertaken on C4-C6 cervical sensorimotor complete subjects. Predictors were based on a broad set of early (<2 weeks) clinical assessments. Endpoints were based on later clinical examinations of upper extremity motor scores and recovery of motor levels, at 6 and 12 months, respectively. Prediction accuracy for each statistical analysis was quantified by resampling techniques. Results. For all settings, overlapping confidence intervals indicated similar prediction accuracy of unbiased recursive partitioning to established statistical approaches. In addition, unbiased recursive partitioning provided a direct way of identification of more homogeneous subgroups. The partitioning is carried out in a data-driven manner, independently from a priori decisions or predefined thresholds. Conclusion. Unbiased recursive partitioning techniques may improve prediction of future clinical endpoints and the planning of future SCI clinical trials by providing easily implementable, data-driven rationales for early patient stratification based on simple decision rules and clinical read-outs.
Background: -Aminobutyric acid (GABA) plasticity plays an important role in stroke motor recovery in a mouse model. However, little is known about changes over time in neuronal excitability mediated by GABA receptors in human stroke patients. Objectives: To establish the mechanism of neuroplasticity during the recovery phase following ischemic stroke by assessing the changes in cerebral GABA activity using [18F]flumazenil ([18F]FMZ) positron emission tomography (PET). Methods: A total of 10 patients with unilateral ischemic stroke were studied at 1 month (T0) and 3 months (T1) postonset using [18F]FMZ PET. Changes in regional GABAergic activity were assessed longitudinally, and values were also compared with those in 15 age-matched controls. Upper-extremity motor function was evaluated using the Fugl-Meyer score (FMS). Results: During the follow-up period, statistical parametric mapping analysis demonstrated a decrease in GABAA receptor availability throughout the cerebral cortex and cerebellum, especially the contralateral hemisphere. GABAA availability in the bilateral primary motor cortex, contralateral supplemental motor cortex, and globus pallidus at T0 was positively correlated with the FMS score at T1. Conclusions: This is the first prospective, controlled longitudinal study showing that the change in GABA receptor availability over time is significantly related to motor recovery after stroke in humans. This work supports the rationale for a novel strategy to promote motor recovery after stroke.
Background. Little is known about the efficacy of language production treatment in subacute severe nonfluent aphasia. Although Melodic Intonation Therapy (MIT) is a language production treatment for this disorder, until now MIT effect studies have focused on chronic aphasia. Purpose. This study examines whether language production treatment with MIT is effective in subacute severe nonfluent aphasia. Methods. A multicenter, randomized controlled trial was conducted in a waiting-list control design: patients were randomly allocated to the experimental group (MIT) or the control group (control intervention followed by delayed MIT). In both groups, therapy started at 2 to 3 months poststroke and was given intensively (5 h/wk) during 6 weeks. In a second therapy period, the control group received 6 weeks of intensive MIT. The experimental group resumed their regular treatment. Assessment was done at baseline (T1), after the first intervention period (T2), and after the second intervention period (T3). Efficacy was evaluated at T2. The impact of delaying MIT on therapy outcome was also examined. Results. A total of 27 participants were included: n = 16 in the experimental group and n = 11 in the control group. A significant effect in favor of MIT on language repetition was observed for trained items, with mixed results for untrained items. After MIT there was a significant improvement in verbal communication but not after the control intervention. Finally, delaying MIT was related to less improvement in the repetition of trained material. Conclusions. In these patients with subacute severe nonfluent aphasia, language production treatment with MIT was effective. Earlier treatment may lead to greater improvement.
Background. An aphasia treatment was designed to shift laterality from the left to right lateral frontal lobe during word production by initiating word-finding trials with complex left-hand movements. Previous findings indicated successful relateralization. Objective. The current study was designed to ascertain whether the shift was attributable to the left-hand movement. Methods. Using stratified random sampling, 14 subjects were equally divided between Intention (IT) and Control (CT) treatments. CT was identical to IT, except with no left-hand movements. Both treatments trained picture naming (phases 1 and 2) and category-member generation (phase 3), each phase lasting 10 sessions. Functional magnetic resonance imaging of category member generation occurred at pretreatment, posttreatment, and 3-month follow-up. Results. IT shifted lateral frontal activity rightward compared with pretreatment both at posttreatment (t = –2.602, df = 6, P < .05) and 3-month follow-up (t = –2.332, df = 5, P < .05), but CT did not. IT and CT yielded similar changes for all picture-naming and category probes. However, IT patients showed gains for untrained category (t = 3.33, df = 6, P < .01) and picture-naming probes (t = 3.77, df = 5, P < .01), but CT patients did not. Conclusions. The rightward shift in lateral frontal activity for IT was because of the left-hand movements. IT evoked greater generalization than CT.
Background. Fear of falling has been identified as an important and independent fall-risk predictor in patients with Parkinson’s disease (PD). However, there are inconsistent findings on the effects of balance and gait training on balance confidence. Objective. To explore whether balance and gait training with augmented feedback can enhance balance confidence in PD patients immediately after treatment and at 3- and 12-month follow-ups. Methods. A total of 51 PD patients were randomly assigned to a balance and gait training (BAL) group or to an active control (CON) group. The BAL group received balance and gait training with augmented feedback, whereas CON participants received lower-limb strength training for 12 weeks. Outcome measures included Activities-Specific Balance Confidence (ABC) Scale, limits-of-stability test, single-leg-stance test, and spatiotemporal gait characteristics. All tests were administered before intervention (Pre), immediately after training (Post), and at 3 months (Post3m) and 12 months (Post12m) after treatment completion. Results. The ABC score improved marginally at Post and significantly at Post3m and Post12m only in the BAL group (P < .017). Both participant groups increased their end point excursion at Post, but only the BAL group maintained the improvement at Post3m. The BAL group maintained significantly longer time-to-loss-of-balance during the single-leg stance test than the CON group at Post3m and Post12m (P < .05). For gait characteristics, both participant groups increased gait velocity, but only the BAL group increased stride length at Post, Post3m, and Post12m (P < .017). Conclusions. Positive findings from this study provide evidence that BAL with augmented feedback could enhance balance confidence and balance and gait performance in patients with PD.
Background. Neglect is associated with disability, unawareness, poor long-term outcome, and dependence from caregivers. No randomized trial has evaluated the effects of smooth pursuit eye movement training (SPT) and visual scanning training (VST) at the bedside on these variables. Objective. To compare the effects of SPT and VST in postacute stroke at 1 month with left neglect. Methods: We carried out an assessor-blinded, randomized controlled trial. The 24 participants were randomly allocated to either SPT or VST (n = 12 each). They received 20 treatment sessions lasting 30 minutes each at the bedside over 4 weeks. Outcome measures included the Functional Neglect Index (FNI) based on 4 tasks: find objects on a tray, stick bisection, picture search, and gaze orientation. In addition, the Unawareness and Behavioral Neglect Index (UBNI) with 6 items about unawareness and 4 about neglect in activities of daily living, the Help index (required assistance in 10 functional activities), the Barthel Index, and the rehabilitation phase were rated by treatment-blinded assessors. Outcome measures were obtained before and immediately after the end of the interventions and at a 2-week follow-up. Results. Significantly greater improvements were obtained after SPT versus VST treatment in the FNI and UBNI, and there were continued improvements selectively in the SPT group 2 weeks later. Conclusions. SPT accelerates recovery from functional neglect and reduces unawareness significantly. Bedside neglect treatment using SPT is effective and feasible early after stroke.
Background. Neurorehabilitation studies suggest that manipulation of error signals during practice can stimulate improvement in coordination after stroke. Objective. To test visual display and robotic technology that delivers augmented error signals during training, in participants with stroke. Methods. A total of 26 participants with chronic hemiparesis were trained with haptic (via robot-rendered forces) and graphic (via a virtual environment) distortions to amplify upper-extremity (UE) tracking error. In a randomized crossover design, the intervention was compared with an equivalent amount of practice without error augmentation (EA). Interventions involved three 45-minute sessions per week for 2 weeks, then 1 week of no treatment, and then 2 additional weeks of the alternate treatment. A therapist provided a visual cursor using a tracking device, and participants were instructed to match it with their hand. Haptic and visual EA was used with blinding of participant, therapist, technician-operator, and evaluator. Clinical measures of impairment were obtained at the beginning and end of each 2-week treatment phase as well as at 1 week and at 45 days after the last treatment. Results. Outcomes showed a small, but significant benefit to EA training over simple repetitive practice, with a mean 2-week improvement in Fugl-Meyer UE motor score of 2.08 and Wolf Motor Function Test of timed tasks of 1.48 s. Conclusions. This interactive technology may improve UE motor recovery of stroke-related hemiparesis.
Background and objectives. The 6-minute walk test (6MWT) is used to measure exercise capacity after stroke. We sought to compare cardiorespiratory responses during the 6MWT with responses to a ramp cycle ergometer test (CET) in community-dwelling individuals with stroke. A secondary objective was to determine the relationship between cardiorespiratory responses during each test and daily physical activity. Methods. Participants completed 3 evaluation sessions. The CET and 6MWT were conducted in 2 separate sessions at least 72 hours apart. Participants wore a portable gas analysis unit (Cosmed K4b2), which also measured heart rate (HR) during the 6MWT. A uniaxial accelerometer (activPAL) was used to measure time spent upright (standing and stepping) over 5 days as an estimate of daily physical activity. Results. Complete CET and 6MWT data were obtained for 16 participants (14 men), a mean ± standard deviation of 2.0 ± 1.1 years after stroke and 71.1 ± 9.7 years of age. Compared with the 6MWT, the CET elicited a higher VO2peak (P = .032), VCO2peak (P = .005), respiratory exchange ratio (P = .015), and self-reported perceived breathing (P < .0001) and leg heaviness (P < .0001) at test completion and a lower HRpeak (P = .029). Except for the first minute, VO2 during the 6MWT was, on average, 80% to 85% of VO2peak from the CET. Among 15 participants, average time spent upright per day was not significantly associated with 6MWT distance (r = 0.447, P = .096) or VO2peak from the CET (r = 0.388, P = .153). Conclusions. Exercise intensity achieved during the 6MWT appeared sufficiently high for aerobic training, assuming CET VO2peak accurately reflects aerobic capacity. The 6MWT may be useful for prescribing aerobic exercise poststroke.
Background. Recent evidence suggests that motor training may be beneficial for slowing the onset of motor impairments in Parkinson’s disease (PD). Objective. To examine the impact of targeted rehabilitation on limb motor and cranial motor function and the corresponding corticospinal and corticobulbar circuits in a rodent model of PD. Methods. Baseline performance of limb (reaching) and cranial (licking) motor function were established prior to and 6 weeks following unilateral intrastriatal 6-hydroxydopamine (6-OHDA) infusions. Animals then received 6 weeks of limb motor rehabilitation (LMR) or cranial motor rehabilitation (CMR), after which motor performance was reassessed. Intracortical microstimulation (ICMS) was used to generate motor maps of corresponding corticospinal (forelimb) and corticobulbar (tongue) movement representations within the motor cortex ipsilateral to the 6-OHDA infusion. Quantitative tyrosine hydroxylase (TH) immunohistochemistry was performed to determine levels of striatal TH depletion in 6-OHDA animals using near infrared densitometry. Results. (1) unilateral intrastriatal dopamine depletion impaired both reaching accuracy and lick force; (2) targeted LMR ameliorated impairments in reaching performance; however, CMR did not improve lick force impairments; (3) unilateral dopamine depletion significantly reduced forelimb but not tongue motor map topography; (4) LMR partially restored forelimb motor maps, whereas CMR did not alter tongue motor maps; and (5) significant correlations were observed between skilled reaching accuracy, forelimb motor map area, and TH depletion, but no relationships were revealed for cranial motor function, motor maps, or TH depletion. Conclusions: These data demonstrate dissociation between striatal dopamine depletion, limb versus cranial motor function, and targeted motor rehabilitation in a rodent model of PD.
Background. Damage to the plasma membrane is a prevalent but often neglected aspect of traumatic brain injury (TBI), which can impair neuronal signaling and hamper neurological recovery. Objective. This study was performed to assess a new noninvasive intervention to counteract peroxidative damage to the phospholipids in the membrane using the powerful action of foods. Although dietary docosahexaenoic acid (C22:6n-3; DHA) provides protection against TBI, the pervasive effects of TBI that cause phospholipid damage, including to DHA, raises concerns about how to preserve DHA in the brain for optimal functional recovery. Methods. Rats were maintained on curcumin and/or DHA-enriched diets for 2 weeks postinjury, and their brains were subjected to analyses. Results. Fluid percussion injury reduced DHA levels as well as levels of enzymes involved in the metabolism of DHA such as FADS2 and 17β-HSD4 and elevated levels of markers of lipid peroxidation such as 4-hydroxy-2-nonenal (4-HNE) and 4-hydroxy-2-hexenal (4-HHE). These effects were counteracted by DHA or curcumin, whereas the combination of curcumin and DHA had an enhanced effect on DHA and 4-HNE. The combination of curcumin and DHA was also efficient in counteracting reductions in the plasticity markers, brain-derived neurotrophic factor and its receptor p-trkB, and learning ability, which had been lessened after TBI. Conclusions. Curcumin complements the action of DHA on TBI pathology, and this property appears to be a viable strategy to counteract neuronal dysfunction after TBI and complement the application of rehabilitative interventions to foster functional recovery.
Background. Kinematic assessment of upper limb motor recovery after stroke may be related to clinical scores while being more sensitive and reliable than clinical evaluation alone. Objective. To identify the potential of kinematics in assessing upper limb recovery early poststroke. Methods. Thirteen patients were included within 1 month poststroke and evaluated once a week for 6 weeks and at 3 months with (a) the Fugl-Meyer Assessment (FMA) and (b) kinematic analysis of reach-to-grasp movements. The link between clinical and kinematic data was identified using mixed model with random coefficient analysis. Results. Movement time, trajectory length, directness, smoothness, mean and maximum velocity of the hand were sensitive to change over time and distinguished between movements of paretic, nonparetic, and healthy control limbs. The FMA score increased with movement smoothness over time, explaining 62.5% of FMA variability. Conclusion. Kinematic analysis of reach-to-grasp movements is relevant to assess upper limb recovery early poststroke, and is linked to the FMA. Kinematics could provide more accurate real-time indicators of patients’ recovery as compared with the sole use of clinical scores, although it remains challenging to establish the universality of the reaching model in relation to motor recovery after stroke.
Background. Extensive neuromotor development occurs early in human life, and the timing of brain injury may affect the resulting motor impairment. In Part I of this series, it was demonstrated that the distribution of weakness in the upper extremity depended on the timing of brain injury in individuals with childhood-onset hemiparesis. Objective. The goal of this study was to characterize how timing of brain injury affects joint torque synergies, or losses of independent joint control. Method. Twenty-four individuals with hemiparesis were divided into 3 groups based on the timing of their injury: before birth (PRE-natal, n = 8), around the time of birth (PERI-natal, n = 8), and after 6 months of age (POST-natal, n = 8). Individuals with hemiparesis and 8 typically developing peers participated in maximal isometric shoulder, elbow, wrist, and finger torque generation tasks while their efforts were recorded by a multiple degree-of-freedom load cell. Motor output in 4 joints of the upper extremity was concurrently measured during 8 primary torque generation tasks to quantify joint torque synergies. Results. There were a number of significant coupling patterns identified in individuals with hemiparesis that differed from the typically developing group. POST-natal differences were most noted in the coupling of shoulder abductors with elbow, wrist, and finger flexors, while the PRE-natal group demonstrated significant distal joint coupling with elbow flexion. Conclusion. The torque synergies measured provide indirect evidence for the use of bulbospinal pathways in the POST-natal group, while those with earlier injury may use relatively preserved ipsilateral corticospinal motor pathways.
Background. Constraint-induced movement therapy (CIMT) has gained emerging evidence and popularity in children with unilateral cerebral palsy (CP). However, many issues remain unanswered regarding the best approach. Objective. This study investigated the additional effects of an intensive therapy program to promote hand function combined with home-based modified CIMT (m-CIMT). Methods. Fifty-one children (mean age 8 years 9 months) were randomized to m-CIMT alone or m-CIMT with intensive therapy (IT). All children had to wear a constraint on the unaffected hand for 1 hour, 5 days/week for 10 weeks. Children in the m-CIMT + IT group also received 3 sessions of 45 minutes weekly of intensive therapy for distal muscle strengthening and hand function, using unimanual and bimanual activities. The Assisting Hand Assessment (AHA) was the primary outcome measure. Secondary outcome measures were muscle tone, strength, Melbourne Assessment, Jebsen–Taylor test, and ABILHAND-Kids questionnaire. Assessments were administered at baseline, after intervention, and at 10-week follow-up. Results. Significant between-group differences in AHA were in favor of the m-CIMT + IT group (P = .04). Both groups demonstrated comparable improvements in muscle tone (P = .002), strength (P < .0001), grip strength (P = .02), and unimanual capacity (Melbourne Assessment and Jebsen–Taylor, P < .0001). Younger children and children with poorer hand function benefited from both interventions, whereas older children and children with better hand function only benefited from the combined approach. Conclusions. The combination of m-CIMT with an intensive therapy program on distal hand function and strength enhances the effects of m-CIMT alone for improving bimanual performance.
Purpose. Impaired economy of gait, prevalent in chronic stroke secondary to residual gait deficits, is associated with intolerance for performing activities of daily living. Gait economy/efficiency is traditionally assessed by determining the rate of oxygen consumption during submaximal treadmill walking. However, the mechanics and energetics of treadmill versus overground walking are very different in stroke survivors with ambulatory deficits. Clearly, overground cardiopulmonary measures are needed to accurately profile movement economy after stroke. An obstacle to obtaining such measures after stroke has been the absence of reliable portable metabolic monitoring equipment. The purpose of this study was to establish the test–retest reliability of a portable metabolic monitoring device during overground walking in hemiparetic stroke survivors. Methods. Twenty-three chronic hemiparetic stroke survivors underwent two 6-minute walk tests while wearing a COSMED K4b2 portable metabolic measurement system. Intraclass correlations coefficients (ICC) were calculated for both cardiopulmonary parameters and distance covered to determine test–retest reliability. An ICC of ≥0.85 was considered reliable. Results. ICCs for relative Vo2 (0.90), absolute Vo2 (0.93), Vco2 (0.93), and minute ventilation (0.95) demonstrated high reliability, but not for heart rate (0.76) or respiratory exchange ratio (0.64). There was no significant difference in the distance each participant walked between the first and second tests, eliminating distance as a potential confounder of our analyses (ICC = 0.99). Conclusions. Our results strongly support the reliability of the K4b2 for quantifying overground gait efficiency after stroke. Use of this device may enable researchers to study how varying poststroke rehabilitation interventions affect this central measure of health and function.
Background. In France in 2009, patients admitted to Multidisciplinary Inpatient Rehabilitation for stroke were sent to a neurological rehabilitation center (NRC) or a general or geriatric rehabilitation (GRC) service. Objective. To describe the functional outcome of stroke patients admitted for rehabilitation in France in 2009, both globally and as a function of the rehabilitation setting (GRC or NRC). Methods. Data from the French Hospital Discharge Diagnosis databases for 2009 were included. Two logistic regression models were used to analyze factors related to improvement in dependence score and discharge home. Odds ratios (ORs) were also calculated. Results. Among the 83 505 survivors of acute stroke in 2009, 28 201 were admitted for rehabilitation (33.8%). Of these, 19 553 went to GRC (69%) and 8648 to NRC (31%). On average, patients admitted to GRC were older (78.6 years vs 66.4 years), P < .001). At the start of rehabilitation, 50% of NRC patients and 56% of GRC patients were heavily dependent, but level of dependence was similar within each age-group. Rehabilitation in NRC lead to a greater probability of functional improvement (OR = 1.75, P < .001) and home discharge (OR = 1.61, P < .001) after adjustment for gender, age, Charlson’s comorbidity index, initial level of dependence, type of stroke, and total length of stay. Conclusion. This study confirms, on a national level, the functional benefit of specialized rehabilitation in NRC. These results should be useful in the improvement of care pathways, organization of rehabilitation, and discharge planning.
Background. Off-the-shelf activity-promoting video games (AVGs) are proposed as a tool for promoting regular physical activity among individuals poststroke. Objective. To characterize the energy expenditure (EE), exercise intensity, and energy metabolism of individuals poststroke, while playing AVGs in different positions, from different consoles, and to compare the performance with comfortable walking and with able-bodied individuals. Methods. Eleven poststroke and 8 able-bodied participants played in standing Wii-Boxing Xbox-Boxing, Wii-Run and Penguin, and also Wii-Boxing in sitting. EE (expressed as metabolic equivalents [METs]); exercise intensity (expressed as %predicted maximal heart rate [HR]), rate of perceived exertion (RPE), and respiratory exchange ratio (RER) were used to characterize the games. Results. Participants’ poststroke EE ranged from 1.81 ± 0.74 to 3.46 ± 1.3 METs and was lower compared with able-bodied participants for Xbox-Boxing (P = .001), Wii-Boxing in standing (P = .01), Run (P < .001), and Penguin (P = .001). Participants’ poststroke exercise intensity ranged from 49.8 ± 9.3 to 64.7 ± 9.3 %predicted maximal HR and was lower compared with able-bodied participants for Xbox-Boxing (P = .007) and Run (P = .005). For participants poststroke, EE of walking at a comfortable did not differ from boxing games in standing or Run. For able-bodied participants only, the EE for Xbox-Boxing was higher than Wii-Boxing (6.5 ± 2.6 vs 4.4 ± 1.1, P = .02). EE was higher in standing versus sitting for poststroke (P = .04) and able-bodied (P = .03) participants. There were no significant group differences for RPEs. RER of playing in sitting approached anaerobic metabolism. Conclusions. Playing upper extremity (ie, Boxing) or mobility (ie, Run) AVGs in standing resulted in moderate EE and intensity for participants poststroke. EE was lower for poststroke than for able-bodied participants.
Background. Turning is a challenging task for stroke patients. Programs that effectively target turning, however, have not been established. Objective. This study examined the effects of a novel turning-based treadmill training on turning performance, gait symmetry, balance, and muscle strength in patients with chronic stroke. Methods. Thirty participants were randomly assigned to the experimental group that received 30 minutes of turning-based treadmill training or to the control group that received 30 minutes of regular treadmill training, followed by a 10-minute general exercise program for 12 sessions over 4 weeks. Primary outcomes (overground turning speed and temporal–spatial characteristics of straight walking) and secondary outcomes (balance and muscle strength) were assessed at baseline, after training, and at 1-month follow-up. Results. Fifteen participants per group were 54.2 ± 9.6 years old, poststroke 2.6 ± 1.9 years, and walked overground at 0.59 ± 0.28 m/s. Sixteen had an ischemic and 14 a hemorrhagic stroke. There were significant interaction effects between groups and time on turning speed regardless of turning direction, straight-walking performance (speed and temporal symmetry), strength of hip muscles and ankle dorsiflexors, and balance control (Berg Balance Scale, weight shifting in the forward direction and vestibular function). Compared with the control group, the experimental group showed greater improvements in these measures following training. These improvements persisted at the 1-month follow-up evaluation. Conclusions. Turning-based treadmill training may be a feasible and effective strategy to improve turning ability, gait symmetry, muscle strength, and balance control for individuals with chronic stroke.
Background. After hemiplegic stroke, people often rely on their unaffected limb to complete activities of daily living. A component of residual motor dysfunction involves learned suppression of movement, termed learned nonuse. Objective. To date, no rodent stroke model of persistent learned nonuse has been described that can facilitate understanding of this phenomenon and test interventions to overcome it. Methods. Rats were trained in the staircase skilled-reaching and limb use asymmetry (cylinder) tasks. Endothelin-1 was injected into the cortex and striatum to create focal ischemia. Starting 7 days poststroke, half of the rats (ipsilateral training; n = 15) were trained to reach for food reward pellets in the tray-reaching task with the ipsilateral forelimb. Training lasted 20 days. Rats in the control group (control; n = 15) did not receive training. All rats then remained in their home cages for an additional 30 days. Performance on the cylinder and staircase tasks was assessed ~2 months poststroke. Results. Ischemia caused significant functional impairments in all rats. Significant contralateral forelimb skilled-reaching recovery was evident in the control group at 2 months but not the ipsilateral training group. There was no difference in performance in the cylinder task. Similarly, the volume of brain injury (~66 mm3) was similar between groups. Ipsilateral forelimb training reduced poststroke motor recovery. Conclusion. This rodent model of persistent nonuse after stroke may be used to further understand mechanisms of learned nonuse as well as to evaluate pharmacological and rehabilitation treatments to overcome it.
Background. Leukoaraiosis describes ischemic white matter lesions, a leading cause of gait disturbance in the elderly. Objective. Our aim was to improve gait and balance in patients with leukoaraiosis by combining a single session of transcranial direct current stimulation (tDCS) and physical training (PT). Methods. We delivered anodal tDCS over midline motor and premotor areas in 9 patients with leukoaraiosis. Patients underwent gait and balance training during tDCS stimulation (real/sham). This was repeated 1 week later with the stimulation crossed-over (sham/real) in a double-blind design. Assessments included gait velocity, stride length, stride length variability (primary gait outcomes), and a quantitative retropulsion test (primary balance outcome). Results. Combining tDCS and PT improved gait velocity, stride length, stride length variability, and balance (all at P ≤ .05). Overall, training without tDCS showed no significant effects. Conclusions. Combined anodal tDCS and PT improves gait and balance in this patient group, suggesting that tDCS could be an effective adjunct to PT in patients with leukoaraiosis, for whom no treatment is currently available.
Background. The properties of the mirror neuron system suggest a new type of upper limb (UL) rehabilitation in children with unilateral cerebral palsy (UCP), based on observation of action therapy followed by execution of a variety of observed movements (AOT). Objective. We tested the effects of AOT in the Upper Limb Children Action Observation Training (UP-CAT) trial. Methods. In a randomized, evaluator-blinded, block-designed trial, 24 UCP children with mild to moderate hand impairment were assigned to 2 groups. The experimental group observed, 1 hour per day for 3 consecutive weeks, video sequences of unimanual or bimanual goal-directed actions and subsequently executed observed actions with the hemiparetic UL or both ULs. The control group performed the same actions in the same order as the experimental sample, but had watched computer games. The Assisting Hand Assessment (AHA) scale was the primary outcome measure; the Melbourne assessment and ABILHAND-Kids were secondary ones. Outcomes were assessed at 1 week (T1), 8 weeks (T2), and 24 weeks (T3) after the end of the training. Results. The experimental group improved more (P = .008) in score changes for the AHA at the primary endpoints T1 (P = .008), T2 (P = .019), and T3 (P = .049). No between-group significant changes were found for ABILHAND-Kids or Melbourne assessment. Conclusions. UP-CAT improved daily UL activities in UCP children, suggesting a new rehabilitation approach based on a neurophysiological model of motor learning.
Background. During upper limb motor recovery after stroke, the greatest improvements occur typically in the first 5 weeks poststroke. It is unclear what patients learn during this early phase of recovery. Objective. To investigate the hypothesis that, early poststroke, patients learn to master the degrees of freedom in the paretic upper limb as reflected by dissociated shoulder and elbow movements during reach-to-grasp. Methods. Thirty-one patients with a first-ever ischemic stroke were included. Repeated 3-dimensional kinematic measurements were conducted at 14, 25, 38, 57, 92, and 189 days poststroke. Trunk, shoulder, elbow, and wrist rotations were measured during a reach-to-grasp task. Using principal component analysis the longitudinal changes in dissociated upper limb movements during reach-to-grasp were investigated. Twelve healthy subjects were included for comparison. Results. The main coordination pattern during reach-to-grasp in patients with stroke and healthy subjects consisted mostly of horizontal shoulder adduction and elbow extension. The standard deviation of this main pattern increased over time, with the largest increase in the first 5 weeks poststroke (F = 5.5, P < .001), but remained smaller than in healthy individuals. The standard deviation increased by 0.46° per day between 14 and 38 days and tapered off to 0.05° per day between 38 and 189 days poststroke. Conclusions. Our results suggest that restitution of motor control by dissociation of shoulder and elbow movements occurs mainly early poststroke. However, compared with healthy adults, most patients did not achieve fully dissociated upper limb movements at 26 weeks poststroke, suggesting that upper limb motor control after stroke remains adaptive.
Background. Physical training might delay the functional deterioration caused by disuse in boys with Duchenne muscular dystrophy (DMD). The "No Use Is Disuse" study is the first explorative, randomized controlled trial in boys with DMD to examine whether assisted bicycle training is feasible, safe, and beneficial. Methods. Ambulatory and recently wheelchair-dependent boys with DMD were allocated to the intervention or control group. The intervention group received assisted bicycle training of the legs and arms during 24 weeks. The control group received the same training after a waiting period of 24 weeks. The primary study outcomes were the Motor Function Measure (MFM) and the Assisted 6-Minute Cycling Test (A6MCT). Group differences were examined by an analysis of covariance. Results. Thirty boys (mean age 10.5 ± 2.6 years, 18 ambulant and 12 wheelchair-dependent) were allocated to the intervention (n = 17) or the control (n = 13) group. All boys in the intervention group (except one) completed the training. After 24 weeks, the total MFM score remained stable in the intervention group, whereas it had significantly decreased in the control group ( = 4.9, 95% confidence interval = 2.2-7.6). No significant group differences were found for the A6MCT. No serious adverse events were observed. Conclusions. Our results suggest that assisted bicycle training of the legs and arms is feasible and safe for both ambulant and wheelchair-dependent children and may decline the deterioration due to disuse. Progressive deterioration, however, may compromise the design of trials for DMD.
Background. Respiratory complications in people with high-level spinal cord injury (SCI) are a major cause of morbidity and mortality, particularly because of a reduced ability to cough as a result of abdominal muscle paralysis. Objective. We investigated the effect of cough training combined with functional electrical stimulation (FES) over the abdominal muscles for 6 weeks to observe whether training could improve cough strength. Methods. Fifteen SCI subjects (C4-T5) trained for 6 weeks, 5 days per week (5 sets of 10 coughs per day) in a randomized crossover design study. Subjects coughed voluntarily at the same time as a train of electrical stimulation was delivered over the abdominal muscles via posterolaterally positioned electrodes (50 Hz, 3 seconds). Measurements were made of esophageal (Pes) and gastric (Pga) expiratory pressures and the peak expiratory flow (PEFcough) produced at the 3 time points of before, during, and after the training. Results. During voluntary coughs, FES cough stimulation improved Pga, Pes, and PEFcough acutely, 20-fold, 4-fold, and 50%, respectively. Six weeks of cough training significantly increased Pga (37.1 ± 2.0 to 46.5 ± 2.9 cm H2O), Pes (35.4 ± 2.7 to 48.1 ± 2.9 cm H2O), and PEFcough (3.1 ± 0.1 to 3.6 ± 0.1 L/s). Cough training also improved pressures and flow during voluntary unstimulated coughs. Conclusions. FES of abdominal muscles acutely increases mechanical output in coughing in high-level SCI subjects. Six weeks of cough training further increases gastric and esophageal cough pressures and expiratory cough flow during stimulated cough maneuvers.
Objective. To assess the safety and efficacy of intrathecal baclofen (ITB) therapy for severe spasticity in patients with upper–motor neuron predominant motor neuron disease (U-MND). Methods. A total of 44 patients with U-MND were referred for discussion of ITB therapy. Baseline and outcomes data were extracted on 35 patients from a clinical spasticity registry at a tertiary referral center. Patients choosing to initiate ITB (n = 20) were compared with those choosing conservative therapy (n = 15). Results. At baseline, lower average pain score in the non-ITB group was the only significant difference between the 2 groups. A significant reduction in pain scores, Modified Ashworth Scale (MAS), Spasm Frequency Scale, and requirement for oral spasticity medications was observed within the ITB group at early and late follow-up. Within the non-ITB group, there was a significant increase in MAS scores between baseline and late follow-up. A statistically significant difference favoring the ITB group was observed for change in MAS score (P < .0001), Numerical Rating Scale pain score (P = .04), dose of oral baclofen (P = .002) and tizanidine (P = .003), and number of oral medications for spasticity (P = .002). There was no difference between the 2 groups in the progression of hip flexor weakness or in the proportion of patients who became nonambulatory. Conclusions. Our findings suggest that ITB can effectively reduce spasticity and related symptoms without compromising function in selected patients with U-MND.
Background. Prophylactic treatment with antiepileptic drugs (AEDs) has been recommended to prevent early seizure onset in patients with traumatic brain injury (TBI). However, the potential neuroprotective and/or detrimental effects of prophylactic AED treatment on behavioral and cognitive function after TBI are not well studied. Objective. To investigate the effects of a novel AED, levitiracetam (LEV), on behavioral and cognitive function after experimental TBI in rats. Methods. Adult male rats were administered LEV (intraperitoneal 50 mg/kg) or vehicle (saline; SL) daily for 20 days beginning 1 day after controlled cortical impact (CCI; 2.8 mm; 4 m/s) or sham surgery. Beam performance (days 1-6), Y-maze (day 7), and Morris water maze (days 14-19) postinjury testing was assessed. Results. Daily LEV treatment improved motor function, increased novel arm exploration in the Y-maze, elicited greater hippocampal cell sparing, and decreased contusion volumes compared with CCI/SL rats. Daily LEV administration also reversed a TBI-induced decrease in regional glutamate transporter expression and neuroplastic marker proteins present 20 days post-CCI. Also, daily LEV treatment decreased regional IL-1β expression after TBI. Conclusions. These results suggest that daily LEV treatment has beneficial effects on histological, molecular, and behavioral elements of neurological recovery after TBI, in part, via modulation of neuroinflammatory and excitatory pathways.
Background. No treatment for auditory neglect and no randomized controlled trial evaluating smooth pursuit eye movement therapy (SPT) for multimodal neglect are available. Objective. To compare the effects of SPT and visual scanning therapy (VST) on auditory and visual neglect in chronic stroke patients with neglect. Methods. A randomized, prospective trial was conducted. Fifty patients with left auditory and visual neglect were randomly assigned. Twenty-four patients completed SPT therapy and 21 patients VST. Five patients (4 VST, 1 SPT) were lost. Each group received 1-hour sessions of neglect therapy for 5 consecutive days totaling 5 hours. Outcome measures in visual neglect (digit cancellation, visuoperceptual- and motor line bisection, paragraph reading) and auditory neglect (auditory midline) were assessed twice before therapy, thereafter, and at 2-week follow-up. The SPT group practiced smooth pursuit eye movements while tracking stimuli moving leftward. The VST group systematically scanned the same but static stimuli. Both groups were divided into subgroups, and effects were separately investigated for mild and severe neglect. Results. Both groups did not differ before therapy in clinical/demographic variables or neglect severity (auditory/visual). After treatment, the SPT group showed significant and lasting improvements in all visual measures and normal performance in the auditory midline. Neither visual nor auditory neglect impairments changed significantly after VST. Moreover, the treatment effect sizes (Cohen’s d) were considerably higher for visual and auditory neglect after SPT versus VST, both for mild and severe neglect. Conclusions. Repetitive contralesional, smooth pursuit training induces superior, multimodal therapeutic effects in mild and severe neglect.
Background. Effective recovery from functional impairments caused by traumatic brain injury (TBI) requires appropriate rehabilitation therapy. Multiple pathways are involved in secondary injury and recovery suggesting a role for multimodal approaches. Objective. Here, we examined the efficacy of the anti-inflammatory agent minocycline and botulinum toxin (botox)–induced limb constraint with structured physical therapy, delivered alone or in combination, after a severe TBI produced by a controlled cortical impact in rats. Methods. Minocycline was administered at 25 mg/kg daily for 2 weeks beginning 1 day after TBI or sham surgery. For constraint/physical therapy, botox-type A was injected into the nonaffected forearm muscle 1 day after injury and 2 weeks of physical therapy commenced at 5 days after injury. Functional evaluations were conducted 8 weeks after injury. Results. Minocycline, either as a monotherapy or as combination treatment with botox/physical therapy significantly reduced impairments of spatial learning and memory in the water maze test, whereas botox/physical therapy reduced forelimb motor asymmetry and improved manual dexterity in the cylinder and vermicelli handling tests, A synergistic effect between the 2 treatments was observed when rats performed tasks requiring dexterity. Inflammation was attenuated in the peri-contusion cortex and hippocampus in all TBI groups receiving mono or combination therapies, though there was no significant difference in lesion size among groups. Conclusion. These data provide a rationale for incorporating anti-inflammatory treatment during rehabilitation therapy.
Background. Upper limb function plays a significant role in enhancing independence for individuals with tetraplegia. However, there is limited knowledge about the specific input of sensorimotor deficits on upper limb function. Thus the theoretical framework designed to develop the Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP) was used as a hypothetical model to analyze the impact of impairment on function. Objective. To define the association of impairment (sensation, strength, and prehension measured by the GRASSP) to upper limb function as defined by functional measures (Capabilities of Upper Extremity Questionnaire, Spinal Cord Independence Measure). Methods. A hypothetical model representing relationships by applying structural equation modeling was used to estimate the effect of the impairment domains in GRASSP on upper limb function. Data collected on 72 chronic individuals with tetraplegia was used to test the hypothetical model. Results. Structural equation modeling confirmed strong associations between sensation, strength, and prehension with upper limb function, and determined 72% of the variance in "sensorimotor upper limb function" was explained by the model. Statistics of fit showed the data did fit the hypothesized model. Sensation and strength influence upper limb function directly and indirectly with prehension as the mediator. Conclusions. The GRASSP is a sensitive diagnostic tool in distinguishing the relative contribution of strength, sensation and prehension to function. Thus, the impact of interventions on specific domains of impairment and related contribution on clinical recovery of the upper limb can be detailed to optimize rehabilitation programs.
Background. Standardizing scoring reduces variability and increases accuracy. A detailed scoring and training method for the Fugl-Meyer motor assessment (FMA) is described and assessed, and implications for clinical trials considered. Methods. A standardized FMA scoring approach and training materials were assembled, including a manual, scoring sheets, and instructional video plus patient videos. Performance of this approach was evaluated for the upper extremity portion. Results. Inter- and intrarater reliability in 31 patients were excellent (intraclass correlation coefficient = 0.98-0.99), validity was excellent (r = 0.74-0.93, P < .0001), and minimal detectable change was low (3.2 points). Training required 1.5 hours and significantly reduced error and variance among 50 students, with arm FMA scores deviating from the answer key by 3.8 ± 6.2 points pretraining versus 0.9 ± 4.9 points posttraining. The current approach was implemented without incident into training for a phase II trial. Among 66 patients treated with robotic therapy, change in FMA was smaller (P ≤ .01) at the high and low ends of baseline FMA scores. Conclusions. Training with the current method improved accuracy, and reduced variance, of FMA scoring; the 20% FMA variance reduction with training would decrease sample size requirements from 137 to 88 in a theoretical trial aiming to detect a 7-point FMA difference. Minimal detectable change was much smaller than FMA minimal clinically important difference. The variation in FMA gains in relation to baseline FMA suggests that future trials consider a sliding outcome approach when FMA is an outcome measure. The current training approach may be useful for assessing motor outcomes in restorative stroke trials.
Background. Many approaches are used to evaluate fall risk. While their properties and performance vary, most reflect performance at a specific moment or are based on subjective self-report. Objective. To quantify fall risk in the home setting using an accelerometer. Methods. Seventy-one community-living older adults were studied. In the laboratory, fall risk was assessed using performance-based tests of mobility (eg, Timed Up and Go) and usual walking abilities were quantified. Subsequently, subjects wore a triaxial accelerometer on their lower back for 3 consecutive days. Acceleration-derived measures were extracted from segments that reflected ambulation. These included total activity duration, number of steps taken, and the amplitude and width at the dominant frequency in the power spectral density, that is, parameters reflecting step-to-step variability. Afterwards, self-report of falls was collected for 6 months to explore the predictive value. Results. Based on a history of 2 or more falls, subjects were classified as fallers or nonfallers. The number of steps during the 3 days was similar (P = .42) in the fallers (7842.1 ± 6135.6) and nonfallers (9055.3 ± 6444.7). Compared with the nonfallers, step-to-step consistency was lower in the fallers in the vertical axis (amplitude fallers, 0.58 ± 0.22 psd; nonfallers, 0.71 ± 0.18 psd; P = .008); in the mediolateral axis, step-to-step consistency was higher in the fallers (P = .014). The 3-day measures improved the identification of past and future falls status (P < .005), compared to performance-based tests. Conclusions. Accelerometer-derived measures based on 3-day recordings are useful for evaluating fall risk as older adults perform daily living activities in their everyday home environment.
Background. Muscle weakness in old Parkinson’s disease (PD) patients has been shown to impair their mobility, although the specific origin of this weakness and its relation to falls has not been well examined in young patients. Objective. This study aimed to analyze the possible contribution of central factors to muscle weakness of the triceps surae and quadriceps femoris muscles in young faller and nonfaller PD patients. Methods. Twenty-six young PD patients (fallers, n = 13 and nonfallers, n = 13) and 15 matched healthy controls performed several isometric maximal voluntary knee extension and plantar flexion contractions (MVC) of the most affected leg on a dynamometer. We estimated the maximal resultant agonist moments, the antagonistic moment of hamstrings and tibialis anterior during MVCs and the activation deficit of the quadriceps femoris and triceps surae muscles. Results. Only the Parkinson fallers showed significantly lower muscle strength, higher antagonistic moments and higher activation deficit compared with controls. Multiple regression analysis showed that the antagonistic moments and the activation deficit explained about 39% and 27%, of the variance in the maximal resultant moments of the knee extensors and the plantar flexors, respectively. Conclusions. Our findings suggest that Parkinson fallers are affected by strength impairments arising from the central nervous system and not from the peripheral muscle contractile capacity, even at early stages of the disease and young age. High-intensity resistance training may help enhance neural drive and decrease unwanted antagonistic moments and reduce the risk of falls.
Background. Amblyopia is a neurodevelopmental disorder of vision that is associated with abnormal patterns of neural inhibition within the visual cortex. This disorder is often considered to be untreatable in adulthood because of insufficient visual cortex plasticity. There is increasing evidence that interventions that target inhibitory interactions within the visual cortex, including certain types of noninvasive brain stimulation, can improve visual function in adults with amblyopia. Objective. We tested the hypothesis that anodal transcranial direct current stimulation (a-tDCS) would improve visual function in adults with amblyopia by enhancing the neural response to inputs from the amblyopic eye. Methods. Thirteen adults with amblyopia participated and contrast sensitivity in the amblyopic and fellow fixing eye was assessed before, during and after a-tDCS or cathodal tDCS (c-tDCS). Five participants also completed a functional magnetic resonance imaging (fMRI) study designed to investigate the effect of a-tDCS on the blood oxygen level–dependent response within the visual cortex to inputs from the amblyopic versus the fellow fixing eye. Results. A subgroup of 8/13 participants showed a transient improvement in amblyopic eye contrast sensitivity for at least 30 minutes after a-tDCS. fMRI measurements indicated that the characteristic cortical response asymmetry in amblyopes, which favors the fellow eye, was reduced by a-tDCS. Conclusions. These preliminary results suggest that a-tDCS deserves further investigation as a potential tool to enhance amblyopia treatment outcomes in adults.
Background. In the past several years, several randomized controlled trials (RCTs) have been reported regarding the efficacy of treadmill-based walking-specific rehabilitation programs, either individually (TT) or combined with body weight support (BWSTT), over control group therapies poststroke. No clear consensus exists as to whether treadmill-based interventions are superior in rehabilitating walking speed (WS) poststroke. Objective. To review published RCTs examining TT and BWSTT poststroke and describe the effects on improving and retaining WS. Methods. A systematic literature search in computerized databases was conducted to identify RCTs whose methodological quality was assessed with PEDro. Pre- and post-WS, change in WS, functional outcomes, and follow-up speed were extracted and calculated from each study. Additionally, statistical results of each study were examined, and the intragroup and intergroup effect sizes (ESintra and ESinter, respectively) were calculated. Results. All studies (8 TT; 7 BWSTT) met the inclusion criteria, and their methodological quality was generally good, with a mean PEDro score 6.9/10. Of the 15 studies, 8 studies (4 TT; 4 BWSTT) reported intragroup significant increases of WS, whereas only 4 (4 TT) found superiority of treadmill interventions. Nine studies demonstrated large ESintra (4 TT; 5 BWSTT), yet only 3 showed large ESinter (1 TT; 2 BWSTT). Four studies (2 TT and 2 BWSTT) reported retention of gains in WS, regardless of intervention. Conclusions. Treadmill-based interventions poststroke may increase and retain WS, but their universal superiority to other control group therapies has failed to be established.
Background. Pain is one of the most common and disabling "nonmotor" symptoms in patients with dystonia. No recent study evaluated the pharmacological or physical therapy approaches to specifically treat dystonic pain symptoms. Objective. To evaluate the effectiveness of KinesioTaping in patients with cervical dystonia (CD) and focal hand dystonia (FHD) on self-reported pain (primary objective) and on sensory functions (secondary objective). Methods. Twenty-five dystonic patients (14 with CD and 11 FHD) entered a randomized crossover pilot study. The patients were randomized to 14-day treatment with KinesioTaping or ShamTaping over neck (in CD) or forearm muscles (in FHD), and after a 30-day washout period, they received the other treatment. The main outcome measures were 3 visual analog scales (VASs) for usual pain, worst pain, and pain relief. Disease severity changes were evaluated by means of the Toronto Western Spasmodic Torticollis Rating Scale (CD) and the Writer’s Cramp Rating Scale (FHD). Furthermore, to investigate possible KinesioTaping-induced effects on sensory functions, we evaluated the somatosensory temporal discrimination threshold. Results. Treatment with KinesioTape induced a decrease in the subjective sensation of pain and a modification in the ability of sensory discrimination, whereas ShamTaping had no effect. A significant, positive correlation was found in both groups of patients between the improvement in the subjective sensation of pain and the reduction of somatosensory temporal discrimination threshold values induced by KinesioTaping. Conclusions. These preliminary results suggest that KinesioTaping may be useful in treating pain in patients with dystonia.
Background. Kinematic movement analysis is increasingly used as an outcome measure in evaluation of upper extremity function after stroke. Little is known, however, about what observed longitudinal changes in kinematics mean in the context of an individual’s functioning. In this study, the responsiveness and expected change in kinematic measures associated with clinically meaningful improvement in the upper extremity were evaluated. Methods. Kinematic movement analysis of a drinking task and Action Research Arm Test (ARAT) were performed early (9 days poststroke) and at 3 months after stroke in 51 subjects. The receiver-operating characteristic curve and linear regression analyses were used to evaluate responsiveness of kinematic parameters. Results. Movement time, smoothness, and trunk displacement discriminated those subjects demonstrating clinically meaningful improvements. Significant associations of 31% to 36% were found between the change in ARAT and kinematic measures. A real clinical improvement in kinematics lies in the range of 2.5 to 5 seconds, 3 to 7 units, and 2 to 5 cm in movement time, smoothness, and trunk displacement, respectively. Conclusions. All kinematic measures reported in this study are responsive measures for capturing improvements in the upper extremity during the first 3 months after stroke. Approximate estimates for the expected change in kinematics associated with clinically meaningful improvement in upper extremity activity capacity illustrate the usefulness of the linear regression analysis for assessing responsiveness. This knowledge facilitates the selection of kinematic measures for clinical and movement analysis research as well as for technology-based devices.
Background. Selective neurotomy is a permanent treatment of focal spasticity, and its effectiveness in treating spastic equinovarus of the foot (SEF) was previously suggested by a few nonrandomized and uncontrolled case-series studies. Objectives. This study is the first assessor-blinded, randomized, controlled trial evaluating the effects of this treatment. Methods. Sixteen chronic stroke patients presenting with SEF were randomized into 2 groups: 8 patients underwent a tibial neurotomy and the remaining 8 received botulinum toxin (BTX) injections. The soleus was treated in all patients, and the tibialis posterior and flexor hallucis longus were treated in about half of patients. The primary outcome was the quantitative measurement of ankle stiffness (L-path), an objective measurement directly related to spasticity. Participants were assessed by a blind assessor before their intervention and at 2 and 6 months after treatment. Evaluations were based on the 3 domains of the International Classification of Functioning, Disability and Health (ICF). Results. Compared with BTX, tibial neurotomy induced a higher reduction in ankle stiffness. Both treatments induced a comparable improvement of ankle kinematics during gait, whereas neither induced muscle weakening. Activity, participation, and quality of life were not significantly modified in either group. Conclusions. This study demonstrates that the tibial nerve neurotomy is an effective treatment of SEF, reducing the impairments observed in chronic stroke patients. Future studies should be conducted to confirm the long-term efficacy based on the ICF domains.
Background. Neurologic music therapy has demonstrated improved walking performance in persons with neurologic disease; however, little evidence supports the use of music with functional resistance exercise to improve motor capacity and daily functions for children with cerebral palsy. Objective. To investigate the effect of additional patterned sensory enhancement (PSE) music combined with exercise for children with spastic diplegia. Methods. An assessor-blind, randomized controlled trial with 6- and 12-week follow-ups was carried out. Thirty-six children with spastic diplegia, aged 5 to 13 years, were assigned to a PSE group (n = 18) or a no-music group (n = 18). Both groups received 6-week, home-based, loaded sit-to-stand exercise, but only the PSE group exercised with prerecorded PSE music. The primary outcome was Gross Motor Function Measure (GMFM). Secondary outcomes included Pediatric Evaluation of Disability Inventory (PEDI) mobility and self-care domains, 1-repetition maximum of sit-to-stand, and walking speeds. Results. Three children did not complete the program. Intention-to-treat analysis showed both groups improved in GMFM D, E, and Goal dimensions; Functional Skills Scales of PEDI mobility domain; and 1-repetition maximum of sit-to-stand at posttest and follow-ups (P ≤ .005). The PSE group improved significantly greater than the no-music group in the GMFM D and Goal dimensions (P < .005) after training, and the improvement persisted for at least 6 or 12 weeks (P ≤ .013). No significant improvements in the rest PEDI scales and walking speeds were found. Conclusions. Adding neurologic music therapy to functional resistance exercise could induce greater improvements in gross motor capacity for children with cerebral palsy.
Background. Neurorehabilitation interventions to improve lower limb function and neuropathic pain have had limited success in people with chronic, incomplete spinal cord injury (iSCI). Objective. We hypothesized that intense virtual reality (VR)–augmented training of observed and executed leg movements would improve limb function and neuropathic pain. Methods. Patients used a VR system with a first-person view of virtual lower limbs, controlled via movement sensors fitted to the patient’s own shoes. Four tasks were used to deliver intensive training of individual muscles (tibialis anterior, quadriceps, leg ad-/abductors). The tasks engaged motivation through feedback of task success. Fourteen chronic iSCI patients were treated over 4 weeks in 16 to 20 sessions of 45 minutes. Outcome measures were 10 Meter Walking Test, Berg Balance Scale, Lower Extremity Motor Score, Spinal Cord Independence Measure, Locomotion and Neuropathic Pain Scale (NPS), obtained at the start and at 4 to 6 weeks before intervention. Results. In addition to positive changes reported by the patients (Patients’ Global Impression of Change), measures of walking capacity, balance, and strength revealed improvements in lower limb function. Intensity and unpleasantness of neuropathic pain in half of the affected participants were reduced on the NPS test. Overall findings remained stable 12 to 16 weeks after termination of the training. Conclusions. In a pretest/posttest, uncontrolled design, VR-augmented training was associated with improvements in motor function and neuropathic pain in persons with chronic iSCI, several of which reached the level of a minimal clinically important change. A controlled trial is needed to compare this intervention to active training alone or in combination.
Background. After stroke, deregulated interhemispheric interactions influence residual paretic hand function. Anodal or cathodal transcranial direct current stimulation (tDCS) can rebalance these abnormal interhemispheric interactions and improve motor function. Objective. We explored whether dual-hemisphere tDCS (dual-tDCS) in participants with chronic stroke can improve fine hand motor function in 2 important aspects: precision grip and dexterity. Methods. In all, 19 chronic hemiparetic individuals with mild to moderate impairment participated in a double-blind, randomized trial. During 2 separate cross-over sessions (real/sham), they performed 10 precision grip movements with a manipulandum and the Purdue Pegboard Test (PPT) before, during, immediately after, and 20 minutes after dual-tDCS applied simultaneously over the ipsilesional (anodal) and contralateral (cathodal) primary motor cortices. Results. The precision grip performed with the paretic hand improved significantly 20 minutes after dual-tDCS, with reduction of the grip force/load force ratio by 7% and in the preloading phase duration by 18% when compared with sham. The dexterity of the paretic hand started improving during dual-tDCS and culminated 20 minutes after the end of dual-tDCS (PPT score +38% vs +5% after sham). The maximal improvements in precision grip and dexterity were observed 20 minutes after dual-tDCS. These improvements correlated negatively with residual hand function quantified with ABILHAND. Conclusions. One bout of dual-tDCS improved the motor control of precision grip and digital dexterity beyond the time of stimulation. These results suggest that dual-tDCS should be tested in longer protocols for neurorehabilitation and with moderate to severely impaired patients. The precise timing of stimulation after stroke onset and associated training should be defined.
Purpose. Walking speed is a cardinal indicator of poststroke gait performance; however, no consensus exists regarding the optimal treatment method(s) for its enhancement. The most widely accepted criterion for establishing the contribution of treatment to walking speed is the gain in speed. The actual speed, however, at the end of the intervention (final speed) may be more important for functional community ambulation. This review examines the contribution of the prevailing methods for gait rehabilitation to final walking speed. Method. Walking speed information was derived from studies included in metaanalyses, systematic reviews, and clinical practice guidelines. Recent references, not included in the mentioned sources, were incorporated in cases when gait speed was an outcome variable. Final speed was assessed by the reported speed values and by inferring the capacity for functional community walking at the end of the intervention period. Results. Similar outcomes for final walking speed were found for the different prevailing treatment methods. Treatment gains were likewise comparable and generally insufficient for upgrading patients’ functional community walking capacity. Conclusions. Different treatment methods exist for poststroke gait rehabilitation. Their availability, mode of application, and costs vary, yet outcomes are largely similar. Therefore, choosing an appropriate method may be guided by a pragmatic approach. Simple "low technology" and conventional exercise to date is at least as efficacious as more complex strategies such as treadmill and robotic-based interventions.