Perspectives of parents partnering with physical therapists to deliver intensive rehabilitation for their young children with perinatal stroke: A qualitative study.

BACKGROUND: Parental participation in their young children's rehabilitation has been promoted to increase intervention intensity, but parents' perspectives on increased involvement remain unclear. The objective of this study was to explore parents' experiences partnering with physical therapists (PTs) to administer early, intensive rehabilitation to their young children with cerebral palsy (CP). METHODS: Twelve mothers and one father of children between 8 months and 3 years old with CP were interviewed. Semistructured interviews were conducted before and after parents partnered with a PT to deliver a 12 week activity-based intervention targeting their child's lower extremities. The intervention occurred in the child's home and in PT clinical sites. Interviews were audio recorded and transcribed verbatim. Interpretive description was used as the methodological framework. RESULTS: The three themes were (1) focus on maximizing the child's potential, (2) participation in intensive rehabilitation is challenging, and (3) the importance of a positive experience with therapy. Families discussed a number of barriers and facilitators to participating in intensive rehabilitation. CONCLUSIONS: These results provide considerations for clinicians and researchers to facilitate meaningful engagement of parents in their young children's rehabilitation. This is especially important with increasing evidence for early, activity-based interventions for young children with CP.

Engaging the Lower Extremity via Active Therapy Early (ELEVATE) Is Feasible and May Improve Gross Motor Function in Children with Spastic Bilateral Cerebral Palsy: A Case Series.

Purpose: The feasibility of ELEVATE with respect to adherence and preliminary efficacy was determined for children with spastic bilateral cerebral palsy (CP) from encephalopathy of prematurity. Methods: A case series was used. Participants were randomized to receive ELEVATE immediately or delay the intervention by 3 months before receiving the intervention. The outcomes included feasibility measures of (1) number of children recruited, (2) percentage of sessions attended, (3) stride counts during the intervention, and preliminary efficacy measures of change over the intervention period in (4) Gross Motor Function Measure-66 (GMFM-66), and (5) kinematics and weight-bearing during treadmill walking. Results: Four boys under 3 years of age participated. All participants tolerated 60-minute intervention sessions four times/week for 12 weeks, and attended 75%-94% (min-max) of the targeted sessions. The median step count per session ranged from 833 to 2484 steps (min-max) during the final week of training. Participants showed an increase in GMFM-66 score of 2.4-7.5 points (min-max) over the 3-month intervention phase, as compared to a decrease of 1.7 for one participant and an increase of 1.3 for another over the delay period. Three participants demonstrated small improvements in their gait with the intervention. Conclusions: Engaging young children with bilateral CP in intensive rehabilitation targeting gross motor function was feasible and demonstrated preliminary efficacy. The results have guided the design of a larger clinical trial to assess efficacy of early, active interventions for children with spastic bilateral CP.

Objectif: les chercheurs ont déterminé la faisabilité d'ELEVATE en matière d'adhésion et d'efficacité préliminaire chez des enfants ayant une paralysie cérébrale spastique bilatérale (PC) causée par une encéphalopathie de la prématurité. Méthodologie: série de cas. Les participants ont été choisis au hasard entre l'utilisation immédiate d'ELEVATE ou son report de trois mois. Les résultats incluaient des mesures de fiabilité, soit 1) le nombre d'enfants recrutés, 2) le pourcentage de séances suivies, 3) le compte des foulées pendant l'intervention et les mesures d'efficacité préliminaire pendant la période de l'intervention sur le plan de 4) la mesure de la fonction motrice globale 66 (GMFM-66) et de 5) la cinématique et la mise en charge pendant la marche sur tapis roulant. Résultats: quatre garçons de moins de trois ans ont participé. Tous ont toléré des séances d'intervention de 60 minutes quatre fois par semaine pendant 12 semaines et ont assisté à 75 % à 94 % (minimum-maximum) des séances ciblées. Le compte médian de foulées par séance se situait entre 833 et 2 484 foulées (minimum­maximum) lors de la dernière semaine d'entraînement. Les participants ont présenté une augmentation de 2,4 à 7,5 points (minimum-maximum) au score du GMFM-66 pendant les trois mois de la phase d'intervention, par rapport à une diminution de 1,7 point chez un participant et à une augmentation de 1,3 point chez un autre pendant la période de report. Trois participants ont démonté de légères améliorations de leur démarche grâce à l'intervention. Conclusions: il est faisable de faire participer des jeunes enfants ayant une PC bilatérale à une réadaptation intensive visant la fonction motrice globale, et cette intervention a une efficacité préliminaire démontrée. Les résultats ont entraîné la conception d'une étude clinique plus vaste pour évaluer l'efficacité d'interventions précoces actives chez les enfants ayant une PC bilatérale spastique.

Neural Plasticity in Spinal and Corticospinal Pathways Induced by Balance Training in Neurologically Intact Adults: A Systematic Review.

Balance training, defined here as training of postural equilibrium, improves postural control and reduces the rate of falls especially in older adults. This systematic review aimed to determine the neuroplasticity induced by such training in younger (18-30 years old) and older adults (≥65 years old). We focused on spinal and corticospinal pathways, as studied with electrophysiology, in people without neurological or other systemic disorders. We were specifically interested in the change in the excitability of these pathways before and after training. Searches were conducted in four databases: MEDLINE, CINAHL, Scopus, and Embase. A total of 1,172 abstracts were screened, and 14 articles were included. Quality of the studies was evaluated with the Downs and Black checklist. Twelve of the studies measured spinal reflexes, with ten measuring the soleus H-reflex. The H-reflex amplitude was consistently reduced in younger adults after balance training, while mixed results were found in older adults, with many showing an increase in the H-reflex after training. The differences in results between studies of younger vs. older adults may be related to the differences in their H-reflexes at baseline, with older adults showing much smaller H-reflexes than younger adults. Five studies measured corticospinal and intracortical excitability using transcranial magnetic stimulation. Younger adults showed reduced corticospinal excitability and enhanced intracortical inhibition after balance training. Two studies on older adults reported mixed results after training. No conclusions could be drawn for corticospinal and intracortical plasticity given the small number of studies. Overall, balance training induced measurable change in spinal excitability, with different changes seen in younger compared to older adults.

Parent-therapist partnership to ELEVATE gross motor function in children with perinatal stroke: protocol for a mixed methods randomized controlled trial.

BACKGROUND: There is increasing evidence for early, active rehabilitation to enhance motor function following early brain injury. This is clear for interventions targeting the upper extremity, whereas passive treatment approaches for the lower extremity persist. The purpose of this trial is to evaluate the effectiveness of early, intensive rehabilitation targeting the lower extremity and delivered in a parent-therapist partnership model for children with perinatal stroke. METHODS: We describe a protocol for a waitlist-control, single-blind, mixed methods effectiveness randomized controlled trial, with an embedded qualitative study using interpretative description. Participants are children with perinatal stroke aged eight months to three years with signs of hemiparesis. Participants will be randomly allocated to an immediate ELEVATE (Engaging the Lower Extremity Via Active Therapy Early) intervention group, or a waitlist-control group, who will receive usual care for six months. The ELEVATE intervention involves one hour of training four days per week for 12 weeks, with a pediatric therapist and a parent or guardian each delivering two sessions per week. The intervention targets the affected lower extremity by progressively challenging the child while standing and walking. The primary outcome measure is the Gross Motor Function Measure-66. Secondary outcomes include the Pediatric Quality of Life Inventory™, Young Children's Participation and Environment Measure, and an instrumented measure of spasticity. A cost-effectiveness analysis and qualitative component will explore benefit to costs ratios and parents' perspectives of early, intensive rehabilitation, and their role as a partner in the rehabilitation, respectively. DISCUSSION: This study has the potential to change current rehabilitation for young children with perinatal stroke if the ELEVATE intervention is effective. The parent interviews will provide further insight into benefits and challenges of a partnership model of rehabilitation. The mixed methods design will enable optimization for transfer of this collaborative approach into physical therapy practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03672864 . Registered 17 September 2018.

Early, Intensive, Lower Extremity Rehabilitation Shows Preliminary Efficacy After Perinatal Stroke: Results of a Pilot Randomized Controlled Trial.

BACKGROUND: Perinatal stroke injures motor regions of the brain, compromising movement for life. Early, intensive, active interventions for the upper extremity are efficacious, but interventions for the lower extremity remain understudied. OBJECTIVE: To determine the feasibility and potential efficacy of ELEVATE-Engaging the Lower Extremity Via Active Therapy Early-on gross motor function. METHODS: We conducted a single-blind, two-arm, randomized controlled trial (RCT), with the Immediate Group receiving the intervention while the Delay Group served as a 3-month waitlist control. A separate cohort living beyond commuting distance was trained by their parents with guidance from physical therapists. Participants were 8 months to 3 years old, with MRI-confirmed perinatal ischemic stroke and early signs of hemiparesis. The intervention was play-based, focused on weight-bearing, balance and walking for 1 hour/day, 4 days/week for 12 weeks. The primary outcome was the Gross Motor Function Measure-66 (GMFM-66). Secondary outcomes included steps and gait analyses. Final follow-up occurred at age 4. RESULTS: Thirty-four children participated (25 RCT, 9 Parent-trained). The improvement in GMFM-66 over 12 weeks was greater for the Immediate than the Delay Group in the RCT (average change 3.4 units higher) and greater in younger children. Average step counts reached 1370-3750 steps/session in the last week of training for all children. Parent-trained children also improved but with greater variability. CONCLUSIONS: Early, activity-intensive lower extremity therapy for young children with perinatal stroke is feasible and improves gross motor function in the short term. Longer term improvement may require additional bouts of intervention. CLINICAL TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov (NCT01773369).

Electrical Stimulation as a Tool to Promote Plasticity of the Injured Spinal Cord.

Unlike their peripheral nervous system counterparts, the capacity of central nervous system neurons and axons for regeneration after injury is minimal. Although a myriad of therapies (and different combinations thereof) to help promote repair and recovery after spinal cord injury (SCI) have been trialed, few have progressed from bench-top to bedside. One of the few such therapies that has been successfully translated from basic science to clinical applications is electrical stimulation (ES). Although the use and study of ES in peripheral nerve growth dates back nearly a century, only recently has it started to be used in a clinical setting. Since those initial experiments and seminal publications, the application of ES to restore function and promote healing have greatly expanded. In this review, we discuss the progression and use of ES over time as it pertains to promoting axonal outgrowth and functional recovery post-SCI. In doing so, we consider four major uses for the study of ES based on the proposed or documented underlying mechanism: (1) using ES to introduce an electric field at the site of injury to promote axonal outgrowth and plasticity; (2) using spinal cord ES to activate or to increase the excitability of neuronal networks below the injury; (3) using motor cortex ES to promote corticospinal tract axonal outgrowth and plasticity; and (4) leveraging the timing of paired stimuli to produce plasticity. Finally, the use of ES in its current state in the context of human SCI studies is discussed, in addition to ongoing research and current knowledge gaps, to highlight the direction of future studies for this therapeutic modality.

Retraining walking over ground in a powered exoskeleton after spinal cord injury: a prospective cohort study to examine functional gains and neuroplasticity.

BACKGROUND: Powered exoskeletons provide a way to stand and walk for people with severe spinal cord injury. Here, we used the ReWalk exoskeleton to determine the training dosage required for walking proficiency, the sensory and motor changes in the nervous system with training, and the functionality of the device in a home-like environment. METHODS: Participants with chronic (> 1 yr) motor complete or incomplete spinal cord injury, who were primarily wheelchair users, were trained to walk in the ReWalk for 12 weeks. Measures were taken before, during, immediately after, and 2-3 months after training. Measures included walking progression, sitting balance, skin sensation, spasticity, and strength of the corticospinal tracts. RESULTS: Twelve participants were enrolled with 10 completing training. Training progression and walking ability: The progression in training indicated about 45 sessions to reach 80% of final performance in training. By the end of training, participants walked at speeds of 0.28-0.60 m/s, and distances of 0.74-1.97 km in 1 h. The effort of walking was about 3.3 times that for manual wheelchair propulsion. One non-walker with an incomplete injury became a walker without the ReWalk after training. Sensory and motor measures: Sitting balance was improved in some, as seen from the limits of stability and sway speed. Neuropathic pain showed no long term changes. Change in spasticity was mixed with suggestion of differences between those with high versus low spasticity prior to training. The strength of motor pathways from the brain to back extensor muscles remained unchanged. Adverse events: Minor adverse events were encountered by the participants and trainer (skin abrasions, non-injurious falls). Field testing: The majority of participants could walk on uneven surfaces outdoors. Some limitations were encountered in home-like environments. CONCLUSION: For individuals with severe SCI, walking proficiency in the ReWalk requires about 45 sessions of training. The training was accompanied by functional improvements in some, especially in people with incomplete injuries. TRIAL REGISTRATION: NCT02322125 Registered 22 December 2014.

Perspectives of people with spinal cord injury learning to walk using a powered exoskeleton.

BACKGROUND: Powered exoskeletons for over ground walking were designed to help people with neurological impairments to walk again. Extended training in powered exoskeletons has led to changes in walking and physiological functions. Few studies have considered the perspective of the participants. The users' perspective is vital for adoption of assistive devices. We explored the expectations and experiences of persons with spinal cord injury, training with the ReWalk exoskeleton. METHODS: A qualitative research design with individual interviews was used. Eleven participants with spinal cord injury, taking part in 12 weeks of 4 times weekly training using the ReWalk, were interviewed before, immediately after, and 2 months after training. Interviews were audio recorded and transcribed verbatim. A six stage approach to thematic analysis was used. RESULTS: The theme consistently expressed was the exoskeleton allowed participants to do everyday activities, like everyone else, such as looking people in the eye or walking outside. Their experiences were captured in three categories: 1) learning, a description of both expectations for learning and perspectives on how learning occurred; 2) changing, perspectives on perceived changes with training; and 3) contributing, which captured participant perspectives on contributing to research, including the giving of direct feedback regarding the exoskeleton (i.e., what worked and what could be changed). CONCLUSIONS: Incorporating the view of the user in the design and refinement of exoskeletons will help ensure that the devices are appropriate for future users. Availability and support for the use of exoskeleton devices in community settings is an interim step to home use as the devices continue to improve. TRIAL REGISTRATION: www.clinicaltrials.gov ( NCT02322125 ). Registered Dec 22, 2014 - Retrospectively registered after the first 4 participants had enrolled in the study.

Cortical electrical stimulation in female rats with a cervical spinal cord injury to promote axonal outgrowth.

Electrical stimulation (ES) to promote corticospinal tract (CST) repair after spinal cord injury (SCI) is underinvestigated. This study is the first to detail intracortical ES of the injured CST. We hypothesize that cortical ES will promote CST collateralization and regeneration, prevent dieback, and improve recovery in an SCI rat model. The CST was transected at the the fourth cervical level in adult female Lewis rats trained in a stairwell grasping task. Animal groups included (a) ES333 (n = 14; 333 Hz, biphasic pulse for 0.2-ms duration every 500 ms, 30 pulses per train); (b) ES20 (n = 14; 20 Hz, biphasic pulse for 0.2-ms duration every 1 s, 60 pulses per train); (c) SCI only (n = 10); and (d) sham (n = 10). ES of the injured forelimb's motor cortex was performed for 30 min immediately prior to SCI. Comparisons between histological data were performed with a 1-way ANOVA or Kruskal-Wallis test, and grasping scores were compared using repeated-measures 2-way ANOVA. Significantly more axonal collateralization was found in ES333 animals compared with controls (p < .01). Axonal dieback analysis revealed ES20 rats to have consistently more dieback than the other groups at all points measured (p < .05). No difference in axonal regeneration was found between groups, nor was there any difference in functional recovery. Cortical ES of the injured CST results in increased collateral sprouting and influences neuroplasticity depending on the ES parameters used. Further investigation regarding optimal parameters and its functional effects is required.

Early Intensive Leg Training to Enhance Walking in Children With Perinatal Stroke: Protocol for a Randomized Controlled Trial.

BACKGROUND: Development of motor pathways is modulated by activity in these pathways, when they are maturing (ie, critical period). Perinatal stroke injures motor pathways, including the corticospinal tracts, reducing their activity and impairing motor function. Current intervention for the lower limb emphasizes passive approaches (stretching, braces, botulinum toxin injections). The study hypothesis was that intensive, early, child-initiated activity during the critical period will enhance connectivity of motor pathways to the legs and improve motor function. OBJECTIVE: The study objective was to determine whether early intervention with intensive activity is better than standard care, intervention delivered during the proposed critical period is better than after, and the outcomes are different when the intervention is delivered by a physical therapist in an institution vs. a parent at home. DESIGN: A prospective, delay-group, single-blind, randomized controlled trial (RCT) and a parallel, cohort study of children living beyond commuting distance and receiving an intervention delivered by their parent. SETTING: The RCT intervention was provided in university laboratories, and parent training was provided in the childs home. PARTICIPANTS: Children 8 months to 3 years old with MRI-confirmed perinatal ischemic stroke and early signs of hemiparesis. INTERVENTION: Intensive, play-based leg activity with weights for the affected leg and foot, 1 hour/day, 4 days/week for 12 weeks. MEASUREMENTS: The primary outcome was the Gross Motor Function Measure-66 score. Secondary outcomes were motion analysis of walking, full-day step counts, motor evoked potentials from transcranial magnetic stimulation, and patellar tendon reflexes. LIMITATIONS: Inter-individual heterogeneity in the severity of the stroke and behavioral differences are substantial but measurable. Differences in intervention delivery and assessment scoring are minimized by standardization and training. CONCLUSIONS: The intervention, contrary to current practice, could change physical therapy interventions for children with perinatal stroke.

Inhibiting cortical protein kinase A in spinal cord injured rats enhances efficacy of rehabilitative training.

Elevated levels of the second messenger molecule cyclic adenosine monophosphate (cAMP) are often associated with neuron sprouting and neurite extension (i.e., neuroplasticity). Phosphokinase A (PKA) is a prominent downstream target of cAMP that has been associated with neurite outgrowth. We hypothesized that rehabilitative motor training following spinal cord injuries promotes neuroplasticity via PKA activation. However, in two independent experiments, inhibition of cortical PKA using Rp-cAMPS throughout rehabilitative training robustly increased functional recovery and collateral sprouting of injured corticospinal tract axons, an indicator of neuroplasticity. Consistent with these in vivo findings, using cultured STHdh neurons, we found that Rp-cAMPS had no effect on the phosphorylation of CREB (cAMP response element-binding protein), a prominent downstream target of PKA, even with the concomitant application of the adenylate cyclase agonist forskolin to increase cAMP levels. Conversely, when cAMP levels were increased using the phosphodiesterase inhibitor IBMX, Rp-cAMPS potently inhibited CREB phosphorylation. Taken together, our results suggest that an alternate cAMP dependent pathway was involved in increasing CREB phosphorylation and neuroplasticity. This idea was supported by an in vitro neurite outgrowth assay, where inhibiting PKA did enhance neurite outgrowth. However, when PKA inhibition was combined with inhibition of EPAC2 (exchange protein directly activated by cAMP), another downstream target of cAMP in neurons, neurite outgrowth was significantly reduced. In conclusion, blocking PKA in cortical neurons of spinal cord injured rats increases neurite outgrowth of the lesioned corticospinal tract fibres and the efficacy of rehabilitative training, likely via EPAC.

A simple analogy for nervous system plasticity after injury.

When considering plasticity, the central nervous system can be viewed as a building block house. After damage, building components might be lost or loosened and may be rearranged by renovation, analogous to neuroplasticity that occurs after central nervous system injury. In both scenarios, the location and severity of damage will determine the efficacy of renovation/rehabilitation and thus the quality of the adapted structure.

Improved single pellet grasping using automated ad libitum full-time training robot.

The single pellet grasping (SPG) task is a skilled forelimb motor task commonly used to evaluate reaching and grasp kinematics and recovery of forelimb function in rodent models of CNS injuries and diseases. To train rats in the SPG task, the animals are usually food restricted then placed in an SPG task enclosure and presented food pellets on a platform located beyond a slit located at the front of the task enclosure for 10-30 min, normally every weekday for several weeks. When the SPG task is applied in studies involving various experimental groups, training quickly becomes labor intensive, and can yield results with significant day-to-day variability. Furthermore, training is frequently done during the animals' light-cycle, which for nocturnal rodents such as mice and rats could affect performance. Here we describe an automated pellet presentation (APP) robotic system to train and test rats in the SPG task that reduces some of the procedural weaknesses of manual training. We found that APP trained rats performed significantly more trials per 24 h period, and had higher success rates with less daily and weekly variability than manually trained rats. Moreover, the results show that success rates are positively correlated with the number of dark-cycle trials, suggesting that dark-cycle training has a positive effect on success rates. These results demonstrate that automated training is an effective method for evaluating and training skilled reaching performance of rats, opening up the possibility for new approaches to investigating the role of motor systems in enabling skilled forelimb use and new approaches to investigating rehabilitation following CNS injury.

Functional testing in animal models of spinal cord injury: not as straight forward as one would think.

When exploring potential treatments for spinal cord injury (SCI), functional recovery is deemed the most relevant outcome measure when it comes to translational considerations. Yet, assessing such recovery and potential treatment effects is challenging and the pitfalls are frequently underestimated. The consequences are that in many cases positive results cannot be reliably replicated, and likely treatments that appear to lack effects have been dismissed prematurely. In this article we review the relationships between lesion location/severity and functional outcomes with specific consideration given to floor and ceiling effects. The roles of compensatory strategies, the challenges of distinguishing them from bona fide recovery, and of comparing function to pre-injury levels given the variability inherent in animal testing are discussed. Ultimately, we offer a series of considerations to enhance the power of functional analysis in animal models of SCI.

Short-term visual deprivation does not enhance passive tactile spatial acuity.

An important unresolved question in sensory neuroscience is whether, and if so with what time course, tactile perception is enhanced by visual deprivation. In three experiments involving 158 normally sighted human participants, we assessed whether tactile spatial acuity improves with short-term visual deprivation over periods ranging from under 10 to over 110 minutes. We used an automated, precisely controlled two-interval forced-choice grating orientation task to assess each participant's ability to discern the orientation of square-wave gratings pressed against the stationary index finger pad of the dominant hand. A two-down one-up staircase (Experiment 1) or a Bayesian adaptive procedure (Experiments 2 and 3) was used to determine the groove width of the grating whose orientation each participant could reliably discriminate. The experiments consistently showed that tactile grating orientation discrimination does not improve with short-term visual deprivation. In fact, we found that tactile performance degraded slightly but significantly upon a brief period of visual deprivation (Experiment 1) and did not improve over periods of up to 110 minutes of deprivation (Experiments 2 and 3). The results additionally showed that grating orientation discrimination tends to improve upon repeated testing, and confirmed that women significantly outperform men on the grating orientation task. We conclude that, contrary to two recent reports but consistent with an earlier literature, passive tactile spatial acuity is not enhanced by short-term visual deprivation. Our findings have important theoretical and practical implications. On the theoretical side, the findings set limits on the time course over which neural mechanisms such as crossmodal plasticity may operate to drive sensory changes; on the practical side, the findings suggest that researchers who compare tactile acuity of blind and sighted participants should not blindfold the sighted participants.