Functioning and activity outcomes of the Akwenda Intervention Program for children and young adults with cerebral palsy in Uganda: A cluster-randomized trial.

AIM: To evaluate the efficacy of the Akwenda Intervention Program on motor, self-care, and social function of children and young people with cerebral palsy (CP). METHOD: This was a cluster-randomized, controlled, single-blinded, intervention study of 100 participants with CP (2-23 years; 52 males) in rural eastern Uganda. Half were allocated to the intervention program, the remainder served as waitlist controls. Gross Motor Function Measure-66 (GMFM-66) and the Ugandan version of Pediatric Evaluation of Disability Inventory (PEDI-UG) were collected before group allocation and after intervention. General linear models and t-tests were used to compare changes within and between groups. Cohen's d estimated the effect size of group differences. Change scores were evaluated by age and mobility subgroups. RESULTS: Significant group by time interactions were found for GMFM-66 (p =0.003) and PEDI-UG outcomes (p <0.001), except mobility, with the intervention group demonstrating greater changes. Both groups increased their scores on the GMFM-66 and child PEDI-UG, while only the intervention group had significant increases in caregiver assistance scores and across all age and mobility subgroups. Cohen's d showed large effect sizes (d >0.8) of differences for PEDI-UG outcomes except mobility. INTERPRETATION: The Akwenda Intervention Program had a large positive impact on functioning and activity across age and mobility levels.

Knee Angle Estimation from Surface EMG during Walking Using Attention-Based Deep Recurrent Neural Networks: Feasibility and Initial Demonstration in Cerebral Palsy.

Accurately estimating knee joint angle during walking from surface electromyography (sEMG) signals can enable more natural control of wearable robotics like exoskeletons. However, challenges exist due to variability across individuals and sessions. This study evaluates an attention-based deep recurrent neural network combining gated recurrent units (GRUs) and an attention mechanism (AM) for knee angle estimation. Three experiments were conducted. First, the GRU-AM model was tested on four healthy adolescents, demonstrating improved estimation compared to GRU alone. A sensitivity analysis revealed that the key contributing muscles were the knee flexor and extensors, highlighting the ability of the AM to focus on the most salient inputs. Second, transfer learning was shown by pretraining the model on an open source dataset before additional training and testing on the four adolescents. Third, the model was progressively adapted over three sessions for one child with cerebral palsy (CP). The GRU-AM model demonstrated robust knee angle estimation across participants with healthy participants (mean RMSE 7 degrees) and participants with CP (RMSE 37 degrees). Further, estimation accuracy improved by 14 degrees on average across successive sessions of walking in the child with CP. These results demonstrate the feasibility of using attention-based deep networks for joint angle estimation in adolescents and clinical populations and support their further development for deployment in wearable robotics.

Early intervention for very young children with or at high likelihood for autism spectrum disorder: An overview of reviews.

AIM: To identify which interventions are supported by evidence and the quality of that evidence in very young children with or at high likelihood for autism spectrum disorder (ASD) to improve child outcomes. METHOD: We conducted an overview of reviews to synthesize early intervention literature for very young children with or at high likelihood for ASD. Cochrane guidance on how to perform overviews of reviews was followed. Comprehensive searches of databases were conducted for systematic reviews and meta-analyses between January 2009 and December 2020. Review data were extracted and summarized and methodological quality was assessed. Primary randomized controlled trial evidence was summarized and risk of bias assessed. This overview of reviews was not registered. RESULTS: From 762 records, 78 full texts were reviewed and seven systematic reviews and meta-analyses with 63 unique studies were identified. Several interventional approaches (naturalistic developmental behavioral intervention, and developmental and behavioral interventions) improved child developmental outcomes. Heterogeneity in design, intervention and control group, dose, delivery agent, and measurement approach was noted. Inconsistent methodological quality and potential biases were identified. INTERPRETATION: While many early interventional approaches have an impact on child outcomes, study heterogeneity and quality had an impact on our ability to draw firm conclusions regarding which treatments are most effective. Advances in trial methodology and design, and increasing attention to mitigating measurement bias, will advance the quality of the ASD early intervention evidence base. WHAT THIS PAPER ADDS: Naturalistic developmental behavioral interventions, as well as developmental and behavioral interventions, improve child outcomes in autism spectrum disorder (ASD). If only randomized controlled trials are considered, guidelines for early intensive behavioral intervention in younger children should be revisited. The greatest intervention impacts were on proximal, intervention-specific outcomes. Inadequacies in the quality of the early ASD intervention evidence base were observed.

Effect of muscle strength training in children and adolescents with spastic cerebral palsy: A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis investigates the effects of strength training program in children and adolescents with cerebral palsy to improve function, activity, and participation. DATA SOURCES: Five electronic databases (MEDLINE-Pubmed, Cochrane Library, PEDro, CINAHL, and SPORTDiscus) were systematically searched for full-text articles published from inception to 30 June 2021. REVIEW METHODS: Randomized controlled trials were included, who compared: (i) child population with spastic cerebral palsy population between 0 and 22 years; (ii) studies in which a muscle strength training program was performed and included dosing information; (iii) studies comparing strength training with other physical therapy technique(s) or untreated control group. Studies with similar outcomes were pooled by calculating standardized mean differences. Risk of bias was assessed with Cochrane Collaboration's tool for assessing the risk of bias and PROSPERO's registration number ID: CRD42020193535. RESULTS: Twenty-seven studies, comprising 847 participants with spastic cerebral palsy. The meta-analyses demonstrated significant standardized mean differences in favor of strength training program compared to other physical therapy technique(s) or untreated control group(s) for muscle strength at the knee flexors, at the knee extensor, at the plantarflexors, maximum resistance, balance, gait speed, GMFM (global, D and E dimension) and spasticity. CONCLUSION: A strength training program has positive functional and activity effects on muscle strength, balance, gait speed, or gross motor function without increasing spasticity for children and adolescents with cerebral palsy in Gross Motor Function Classification System levels I, II, and III when adequate dosage and specific principles are utilized.

Determining optimal mobile neurofeedback methods for motor neurorehabilitation in children and adults with non-progressive neurological disorders: a scoping review.

BACKGROUND: Brain-computer interfaces (BCI), initially designed to bypass the peripheral motor system to externally control movement using brain signals, are additionally being utilized for motor rehabilitation in stroke and other neurological disorders. Also called neurofeedback training, multiple approaches have been developed to link motor-related cortical signals to assistive robotic or electrical stimulation devices during active motor training with variable, but mostly positive, functional outcomes reported. Our specific research question for this scoping review was: for persons with non-progressive neurological injuries who have the potential to improve voluntary motor control, which mobile BCI-based neurofeedback methods demonstrate or are associated with improved motor outcomes for Neurorehabilitation applications? METHODS: We searched PubMed, Web of Science, and Scopus databases with all steps from study selection to data extraction performed independently by at least 2 individuals. Search terms included: brain machine or computer interfaces, neurofeedback and motor; however, only studies requiring a motor attempt, versus motor imagery, were retained. Data extraction included participant characteristics, study design details and motor outcomes. RESULTS: From 5109 papers, 139 full texts were reviewed with 23 unique studies identified. All utilized EEG and, except for one, were on the stroke population. The most commonly reported functional outcomes were the Fugl-Meyer Assessment (FMA; n = 13) and the Action Research Arm Test (ARAT; n = 6) which were then utilized to assess effectiveness, evaluate design features, and correlate with training doses. Statistically and functionally significant pre-to post training changes were seen in FMA, but not ARAT. Results did not differ between robotic and electrical stimulation feedback paradigms. Notably, FMA outcomes were positively correlated with training dose. CONCLUSION: This review on BCI-based neurofeedback training confirms previous findings of effectiveness in improving motor outcomes with some evidence of enhanced neuroplasticity in adults with stroke. Associative learning paradigms have emerged more recently which may be particularly feasible and effective methods for Neurorehabilitation. More clinical trials in pediatric and adult neurorehabilitation to refine methods and doses and to compare to other evidence-based training strategies are warranted.

Early intervention evidence for infants with or at risk for cerebral palsy: an overview of systematic reviews.

AIM: To perform an overview of systematic reviews and more recent randomized controlled trials (RCTs) on early motor interventions in infants aged 0 to 3 years with or at risk of cerebral palsy to inform current clinical and research efforts and provide a benchmark to assess future interventions ideally initiated within the first 6 months. METHOD: Standardized searches of the PubMed, Embase, Scopus, and Web of Science databases were conducted for systematic reviews (2009-2020) and RCTs (2015-2020). RESULTS: From 840 unique records, 31 full texts were reviewed, yielding three systematic reviews encompassing 46 studies, 16 with comparison groups, and six additional RCTs that met the criteria. Two enrichment- and activity-based approaches had medium effect sizes on motor development, only one with low risk of bias; two others had large task-specific effect sizes but some bias concerns; and three enriched environment studies with some bias concerns had medium effect sizes on cognitive development. Most had small or no effect sizes, bias concerns, and uncertain diagnostic determinations. INTERPRETATION: Data synthesis revealed limited data quantity and quality, and suggest, although not yet confirmed, greater benefit from early versus later intervention. Research efforts with greater early diagnostic precision and earlier intervention are accelerating, which may transform future outcomes and practices. What this paper adds For over 50% of trials within the reviews, the intervention was compared to standard care with only two showing efficacy. Similar to results in older children, constraint-induced movement therapy (CIMT) emerged as efficacious with high effect sizes. CIMT was not superior to similarly intense bimanual training or occupational therapy. Goals-Activity-Motor Enrichment intervention initiated before 5 months of age was superior to equally intense standard care. Several other enriched environment strategies promoted cognitive and/or motor development.

Systematic Review of Clinical Guidelines Related to Care of Individuals With Cerebral Palsy as Part of the World Health Organization Efforts to Develop a Global Package of Interventions for Rehabilitation.

OBJECTIVE: The World Health Organization's (WHO) Rehabilitation 2030 initiative is working to develop a set of evidence-based interventions selected from clinical practice guidelines for Universal Health Coverage. As an initial step, the WHO Rehabilitation Programme and Cochrane Rehabilitation convened global content experts to conduct systematic reviews of clinical practice guidelines for 20 chronic health conditions, including cerebral palsy. DATA SOURCES: Six scientific databases (Pubmed, EMBASE, Scopus, Web of Science, PEDro, CINAHL), Google Scholar, guideline databases, and professional society websites were searched. STUDY SELECTION: A search strategy was implemented to identify clinical practice guidelines for cerebral palsy across the lifespan published within 10 years in English. Standardized spreadsheets were provided for process documentation, data entry, and tabulation of the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. Each step was completed by 2 or more group members, with disagreements resolved by discussion. Initially, 13 guidelines were identified. Five did not meet the AGREE II established threshold or criteria for inclusion. Further review by the WHO eliminated 3 more, resulting in 5 remaining guidelines. DATA EXTRACTION: All 339 recommendations from the 5 final guidelines, with type (assessment, intervention, or service), strength, and quality of evidence, were extracted, and an International Classification of Functioning, Disability and Health Functioning (ICF) category was assigned to each. DATA SYNTHESIS: Most guidelines addressed mobility functions, with comorbid conditions and lifespan considerations also included. However, most were at the level of body functions. No guideline focused specifically on physical or occupational therapies to improve activity and participation, despite their prevalence in rehabilitation. CONCLUSIONS: Despite the great need for high quality guidelines, this review demonstrated the limited number and range of interventions and lack of explicit use of the ICF during development of guidelines identified here. A lack of guidelines, however, does not necessarily indicate a lack of evidence. Further evidence review and development based on identified gaps and stakeholder priorities are needed.

Effects of Orthoses on Standing Postural Control and Muscle Activity in Children With Cerebral Palsy.

PURPOSE: This exploratory study assessed postural control and muscle activity in children with cerebral palsy while standing barefoot (BF), in prescribed ankle-foot orthoses (AFOs) and in distal control orthoses (DCOs), which stabilized foot-ankle and deliberately aligned the shank. METHODS: This within-subject study evaluated 10 participants, Gross Motor Functional Classification System level III, across the 3 ankle-foot conditions in: (1) static standing duration and (2) modified Clinical Test of Sensory Interaction on Balance with electromyography (EMG) on 7 muscles. RESULTS: Participants had significantly decreased center of gravity (COG) velocity sway in DCO versus BF and AFO, decreased loss of balance (LOB), and increased standing for DCO versus BF. DCO had minimal effect on EMG activity. CONCLUSIONS: DCO provided significant stabilizing effects on COG sway velocity, standing duration, and LOB. DCO may be effective in balance training. It is unclear whether benefit was derived from stabilization of the ankle joint, the resultant shank alignment, or both.

Brain activation patterns underlying upper limb bilateral motor coordination in unilateral cerebral palsy: an fNIRS study.

AIM: To explore cortical activation during bimanual tasks and functional correlates in unilateral cerebral palsy (CP). METHOD: This cross-sectional study included eight participants with unilateral CP (six females, two males; mean age [SD] 20y 10mo [5y 10mo], 13y 8mo-31y 6mo) in Manual Ability Classification System levels II to III and nine age-matched participants with typical development (seven females, two males; mean age [SD] 17y 8mo [5y 7mo], 9y 4mo-24y 2mo). They performed bimanual symmetric squeezing (BSS) and bimanual asymmetric squeezing (BAS) tasks at 1Hz, and a pouring task with dominant hand (DPour) and a pouring task with non-dominant hand (NDPour) at 0.67Hz, all while a custom array of functional near-infrared spectroscopy (fNIRS) optodes were placed over their sensorimotor area. Mixed-effects were used to contrast groups, tasks, and hemispheres (corrected p-values [q] reported). Analysis of variance and t-tests compared performance measures across groups and tasks. RESULTS: Participants with unilateral CP showed greater activation in both hemispheres during BAS (non-lesioned: q<0.001; lesioned: q<0.001), and in the lesioned hemisphere during BSS (q<0.001), DPour (q=0.02), and NDPour (q=0.02) than those with typical development. The lesioned hemisphere in unilateral CP showed more activity than the non-lesioned one (BSS: q=0.01; BAS: q=0.009; NDPour: q=0.04). During BAS, higher cortical activity correlated with more synchronous arm activation (r=0.79; p=0.02); activity lateralized towards the non-lesioned hemisphere correlated with better Pediatric Evaluation of Disability Inventory computer adaptive test scores (r=0.81; p=0.03). INTERPRETATION: Results suggest abnormally increased sensorimotor cortical activity in unilateral CP, with implications to be investigated. WHAT THIS PAPER ADDS: Cortical activity in manual tasks is described with functional near-infrared spectroscopy in typical and atypical cohorts. Activation levels in unilateral cerebral palsy appear to escalate with task difficulty. Increased brain activity may be associated with poorer selective manual control. Specific patterns of brain activity may be related to impaired bimanual function.

Toward a hybrid exoskeleton for crouch gait in children with cerebral palsy: neuromuscular electrical stimulation for improved knee extension.

BACKGROUND: Neuromuscular Electrical Stimulation (NMES) has been utilized for many years in cerebral palsy (CP) with limited success despite its inherent potential for improving muscle size and/or strength, inhibiting or reducing spasticity, and enhancing motor performance during functional activities such as gait. While surface NMES has been shown to successfully improve foot drop in CP and stroke, correction of more complex gait abnormalities in CP such as flexed knee (crouch) gait remains challenging due to the level of stimulation needed for the quadriceps muscles that must be balanced with patient tolerability and the ability to deliver NMES assistance at precise times within a gait cycle. METHODS: This paper outlines the design and evaluation of a custom, noninvasive NMES system that can trigger and adjust electrical stimulation in real-time. Further, this study demonstrates feasibility of one possible application for this digitally-controlled NMES system as a component of a pediatric robotic exoskeleton to provide on-demand stimulation to leg muscles within specific phases of the gait cycle for those with CP and other neurological disorders who still have lower limb sensation and volitional control. A graphical user interface was developed to digitally set stimulation parameters (amplitude, pulse width, and frequency), timing, and intensity during walking. Benchtop testing characterized system delay and power output. System performance was investigated during a single session that consisted of four overground walking conditions in a 15-year-old male with bilateral spastic CP, GMFCS Level III: (1) his current Ankle-Foot Orthosis (AFO); (2) unassisted Exoskeleton; (3) NMES of the vastus lateralis; and (4) NMES of the vastus lateralis and rectus femoris. We hypothesized in this participant with crouch gait that NMES triggered with low latency to knee extensor muscles during stance would have a modest but positive effect on knee extension during stance. RESULTS: The system delivers four channels of NMES with average delays of 16.5 ± 13.5 ms. Walking results show NMES to the vastus lateralis and rectus femoris during stance immediately improved mean peak knee extension during mid-stance (p = 0.003*) and total knee excursion (p = 0.009*) in the more affected leg. The electrical design, microcontroller software and graphical user interface developed here are included as open source material to facilitate additional research into digitally-controlled surface stimulation ( github.com/NIHFAB/NMES ). CONCLUSIONS: The custom, digitally-controlled NMES system can reliably trigger electrical stimulation with low latency. Precisely timed delivery of electrical stimulation to the quadriceps is a promising treatment for crouch. Our ultimate goal is to synchronize NMES with robotic knee extension assistance to create a hybrid NMES-exoskeleton device for gait rehabilitation in children with flexed knee gait from CP as well as from other pediatric disorders. TRIAL REGISTRATION: clinicaltrials.gov, ID: NCT01961557 . Registered 11 October 2013; Last Updated 27 January 2020.

Quantification of Muscle Tissue Properties by Modeling the Statistics of Ultrasound Image Intensities Using a Mixture of Gamma Distributions in Children With and Without Cerebral Palsy.

OBJECTIVES: To investigate whether quantitative ultrasound (US) imaging, based on the envelope statistics of the backscattered US signal, can describe muscle properties in typically developing children and those with cerebral palsy (CP). METHODS: Radiofrequency US data were acquired from the rectus femoris muscle of children with CP (n = 22) and an age-matched cohort without CP (n = 14) at rest and during maximal voluntary isometric contraction. A mixture of gamma distributions was used to model the histogram of the echo intensities within a region of interest in the muscle. RESULTS: Muscle in CP had a heterogeneous echo texture that was significantly different from that in healthy controls (P < .001), with larger deviations from Rayleigh scattering. A mixture of 2 gamma distributions showed an excellent fit to the US intensity, and the shape and rate parameters were significantly different between CP and control groups (P < .05). The rate parameters for both the single gamma distribution and mixture of gamma distributions were significantly higher for contracted muscles compared to resting muscles, but there was no significant interaction between these factors (CP and muscle contraction) for a mixed-model analysis of variance. CONCLUSIONS: Ultrasound tissue characterization indicates a more disorganized architecture and increased echogenicity in muscles in CP, consistent with previously documented increases in fibrous infiltration and connective tissue changes in this population. Our results indicate that quantitative US can be used to objectively differentiate muscle architecture and tissue properties.

Rehabilitation Research at the National Institutes of Health: Moving the Field Forward (Executive Summary).

Approximately 53 million Americans live with a disability. For decades, the National Institutes of Health (NIH) has been conducting and supporting research to discover new ways to minimize disability and enhance the quality of life of people with disabilities. After the passage of the Americans With Disabilities Act, NIH established the National Center for Medical Rehabilitation Research, with the goal of developing and implementing a rehabilitation research agenda. Currently, 17 institutes and centers at NIH invest more than $500 million per year in rehabilitation research. Recently, the director of NIH, Francis Collins, appointed a Blue Ribbon Panel to evaluate the status of rehabilitation research across institutes and centers. As a follow-up to the work of that panel, NIH recently organized a conference, "Rehabilitation Research at NIH: Moving the Field Forward." This report is a summary of the discussions and proposals that will help guide rehabilitation research at NIH in the near future.

Effects of a rapid-resisted elliptical training program on motor, cognitive and neurobehavioral functioning in adults with chronic traumatic brain injury.

This small clinical trial utilized a novel rehabilitation strategy, rapid-resisted elliptical training, in an effort to increase motor, and thereby cognitive, processing speed in ambulatory individuals with traumatic brain injury (TBI). As an initial step, multimodal functional abilities were quantified and compared in 12 ambulatory adults with and 12 without TBI. After the baseline assessment, the group with TBI participated in an intensive 8-week daily exercise program using an elliptical trainer and was reassessed after completion and at an 8-week follow-up. The focus of training was on achieving a fast movement speed, and once the target was reached, resistance to motion was increased in small increments to increase intensity of muscle activation. Primary outcomes were: High-Level Mobility Assessment Tool (HiMAT), instrumented balance tests, dual-task (DT) performance and neurobehavioral questionnaires. The group with TBI had poorer movement excursion during balance tests and poorer dual-task (DT) performance. After training, balance reaction times improved and were correlated with gains in the HiMAT and DT. Sleep quality also improved and was correlated with improved depression and learning. This study illustrates how brain injury can affect multiple linked aspects of functioning and provides preliminary evidence that intensive rapid-resisted training has specific positive effects on dynamic balance and more generalized effects on sleep quality in TBI.

Deficits in motor abilities for multi-finger force control in hemiparetic stroke survivors.

The ability to control redundant motor effectors is one of hallmarks in human motor control, and the topic has been studied extensively over several decades since the initial inquiries proposed by Nicholi Bernstein. However, our understanding of the influence of stroke on the control of redundant motor systems is very limited. This study aimed to investigate the effect of stroke-related constraints on multi-finger force control abilities in a visuomotor task. Impaired (IH) and less-impaired hands (LH) of 19 hemiparetic stroke survivors and 19 age-matched control subjects were examined. Each hand repeatedly produced isometric forces to match a target force of 5 N shown on a computer screen using all four fingers. The hierarchical variability decomposition (HVD) model was used to separate force-matching errors (motor performance) into task-relevant measures (accuracy, steadiness, and reproducibility). Task-irrelevant sources of variability in individual finger force profiles within and between trials (flexibility and multiformity) were also quantified. The IH in the stroke survivors showed deficits in motor performance attributed mainly to lower accuracy and reproducibility as compared to control hands (p < 0.05). The LH in stroke survivors showed lower reproducibility and both hands in stroke also had higher multiformity than the control hands (p < 0.05). The findings from our HVD model suggest that accuracy, reproducibility, and multiformity were mainly impaired during force-matching task in the stroke survivors. The specific motor deficits identified through the HVD model with the new conceptual framework may be considered as critical factors for scientific investigation on stroke and evidence-based rehabilitation of this population.

2014 section on pediatrics knowledge translation lecture: clinicians and researchers on the same path toward facilitating family goals for mobility and participation.

BACKGROUND: The knowledge translation (KT) lecture at the Combined Sections Meeting 2014 was a personal perspective from a researcher who had been a therapist and a longtime clinician, now a PhD candidate. OBJECTIVE: To better integrate research and clinical care, KT is a seamless rather than separate process. KEY POINTS: Knowledge translation can be enhanced by improved receptivity to evidence, and increasing use of research designs that encourage and even require clinician involvement, from single-subject designs to large-scale pragmatic trials. Clinical practice databases and hiring therapists to provide intervention in research efforts also serve to integrate research and clinical care. Limitations of applying mean group research results to an individual patient were also discussed and suggest an important unanswered topic for future research. CONCLUSION: We all need to assume responsibility for the researcher-clinician partnership, making our jobs more joyful and fulfilling, and hopefully the biggest beneficiaries will be our current and future patients.

Shoulder strength profiles in children with and without brachial PLEXUS PALSY.

INTRODUCTION: We characterized bilateral shoulder strength and the balance of antagonist/agonist muscle pairs in children with brachial plexus palsy (BPP) and with typical development (TD). METHODS: In 15 children with unilateral BPP and 11 with TD, bilateral maximal isometric shoulder strength in flexion/extension, internal/external rotation, and abduction/adduction was recorded using a hand-held dynamometer. Correlation between strength and active range of motion were evaluated using the Mallet score. RESULTS: Children with BPP had strength asymmetry in all muscles, whereas children with TD had significant strength asymmetry for flexors and abductors. In children with BPP, extensors and external rotators were the weakest muscles, leading to sagittal and transverse plane muscle imbalances. Higher strength values were related to better active range of motion. CONCLUSIONS: This study highlights the importance of documenting shoulder strength profiles in children with BPP which may help predict deformity development.

Meaningfulness of mean group results for determining the optimal motor rehabilitation program for an individual child with cerebral palsy.

As research on the efficacy or effectiveness of interventions to improve motor functioning in cerebral palsy (CP) has accumulated and been incorporated into systematic reviews, the foundation for evidence-based practice in CP is growing. To determine whether an intervention is effective, clinical trials report mean group differences. However, even if a statistically significant mean group effect is found, this does not imply that this intervention was effective for each study participant or ensure positive outcomes for all with CP. A personalized approach to medical care is currently being advocated based primarily on increasingly recognized genetic variations in individual responses to medications and other therapies. A similar approach is also warranted, and perhaps more justifiable, in CP which includes a heterogeneous group of disorders. Even interventions deemed highly effective in CP demonstrate a range of individual responses along a continuum from a negative or negligible response to a strong positive effect, the bases for which remain incompletely understood. This narrative review recommends that the next critical step in advancing evidence-based practice is to implement research strategies to identify patient factors that predict treatment responses so we can not only answer the question 'what works', but also 'what works best, for whom'.