Number 11

This perspective outlines the theoretical basis for the presentation with the same name as the second part of this title, which was given at the III STEP conference in July 2005. It elaborates on the take-home message from that talk, which was to promote activity in children and adults with cerebral palsy and other central nervous system disorders. The author proposes that the paradigm for physical therapist management of cerebral palsy needs to shift from traditional or "packaged" approaches to a more focused and proactive approach of promoting activity through more intense active training protocols, lifestyle modifications, and mobility-enhancing devices. Increased motor activity has been shown to lead to better physical and mental health and to augment other aspects of functioning such as cognitive performance, and more recently has been shown to promote neural and functional recovery in people with damaged nervous systems. Although the benefits of fairly intense physical exercise programs such as strength training are becoming increasingly well recognized, few studies on the positive effects of generalized activity programs have been conducted in individuals with cerebral palsy. More research is needed and is currently under way to design and test the efficacy of activity-based strategies in cerebral palsy. [Damiano DL. Activity, activity, activity: rethinking our physical therapy approach to cerebral palsy. Phys Ther. 2006;86:1534 -154

Kinematic Foot Types in Youth with Equinovarus Secondary to Hemiplegia

Background Elevated kinematic variability of the foot and ankle segments exists during gait among individuals with equinovarus secondary to hemiplegic cerebral palsy (CP). Clinicians have previously addressed such variability by developing classification schemes to identify subgroups of individuals based on their kinematics. Objective To identify kinematic subgroups among youth with equinovarus secondary to CP using 3-dimensional multi-segment foot and ankle kinematics during locomotion as inputs for principal component analysis (PCA), and K-means cluster analysis. Methods In a single assessment session, multi-segment foot and ankle kinematics using the Milwaukee Foot Model (MFM) were collected in 24 children/adolescents with equinovarus and 20 typically developing children/adolescents. Results PCA was used as a data reduction technique on 40 variables. K-means cluster analysis was performed on the first six principal components (PCs) which accounted for 92% of the variance of the dataset. The PCs described the location and plane of involvement in the foot and ankle. Five distinct kinematic subgroups were identified using K-means clustering. Participants with equinovarus presented with variable involvement ranging from primary hindfoot or forefoot deviations to deformtiy that included both segments in multiple planes. Conclusion This study provides further evidence of the variability in foot characteristics associated with equinovarus secondary to hemiplegic CP. These findings would not have been detected using a single segment foot model. The identification of multiple kinematic subgroups with unique foot and ankle characteristics has the potential to improve treatment since similar patients within a subgroup are likely to benefit from the same intervention(s)

A Pediatric Knee Exoskeleton With Real-Time Adaptive Control for Overground Walking in Ambulatory Individuals With Cerebral Palsy

Gait training via a wearable device in children with cerebral palsy (CP) offers the potential to increase therapy dosage and intensity compared to current approaches. Here, we report the design and characterization of a pediatric knee exoskeleton (P.REX) with a microcontroller based multi-layered closed loop control system to provide individualized control capability. Exoskeleton performance was evaluated through benchtop and human subject testing. Step response tests show the averaged 90% rise was 26 ± 0.2 ms for 5 Nm, 22 ± 0.2 ms for 10 Nm, 32 ± 0.4 ms for 15 Nm. Torque bandwidth of P.REX was 12 Hz and output impedance was less than 1.8 Nm with control on (Zero mode). Three different control strategies can be deployed to apply assistance to knee extension: state-based assistance, impedance-based trajectory tracking, and real-time adaptive control. One participant with typical development (TD) and one participant with crouch gait from CP were recruited to evaluate P.REX in overground walking tests. Data from the participant with TD were used to validate control system performance. Kinematic and kinetic data were collected by motion capture and compared to exoskeleton on-board sensors to evaluate control system performance with results demonstrating that the control system functioned as intended. The data from the participant with CP are part of a larger ongoing study. Results for this participant compare walking with P.REX in two control modes: a state-based approach that provided constant knee extension assistance during early stance, mid-stance and late swing (Est+Mst+Lsw mode) and an Adaptive mode providing knee extension assistance proportional to estimated knee moment during stance. Both were well tolerated and significantly improved knee extension compared to walking without extension assistance (Zero mode). There was less reduction in gait speed during use of the adaptive controller, suggesting that it may be more intuitive than state-based constant assistance for this individual. Future work will investigate the effects of exoskeleton assistance during overground gait training in children with neurological disorders and will aim to identify the optimal individualized control strategy for exoskeleton prescription

Functional and Structural Brain Connectivity in Children With Bilateral Cerebral Palsy Compared to Age-Related Controls and in Response to Intensive Rapid-Reciprocal Leg Training

BackgroundCompared to unilateral cerebral palsy (CP), less is known about brain reorganization and plasticity in bilateral CP especially in relation or response to motor training. The few trials that reported brain imaging results alongside functional outcomes include a handful of studies in unilateral CP, and one pilot trial of three children with bilateral CP. This study is the first locomotor training randomized controlled trial (RCT) in bilateral CP to our knowledge reporting brain imaging outcomes.MethodsObjective was to compare MRI brain volumes, resting state connectivity and white matter integrity using DTI in children with bilateral CP with PVL and preterm birth history (<34 weeks), to age-related controls, and from an RCT of intensive 12 week rapid-reciprocal locomotor training using an elliptical or motor-assisted cycle. We hypothesized that connectivity in CP compared to controls would be greater across sensorimotor-related brain regions and that functional (resting state) and structural (fractional anisotropy) connectivity would improve post intervention. We further anticipated that baseline and post-intervention imaging and functional measures would correlate.ResultsImages were acquired with a 3T MRI scanner for 16/27 children with CP in the trial, and 18 controls. No conclusive evidence of training-induced neuroplastic effects were seen. However, analysis of shared variance revealed that greater increases in precentral gyrus connectivity with the thalamus and pons may be associated with larger improvements in the trained device speed. Exploratory analyses also revealed interesting potential relationships between brain integrity and multiple functional outcomes in CP, with functional connectivity between the motor cortex and midbrain showing the strongest potential relationship with mobility. Decreased posterior white matter, corpus callosum and thalamic volumes, and FA in the posterior thalamic radiation were the most prominent group differences with corticospinal tract differences notably not found.ConclusionsResults reinforce the involvement of sensory-related brain areas in bilateral CP. Given the wide individual variability in imaging results and clinical responses to training, a greater focus on neural and other mechanisms related to better or worse outcomes is recommended to enhance rehabilitation results on a patient vs. group level

Early Intervention for Children Aged 0 to 2 Years With or at High Risk of Cerebral Palsy International Clinical Practice Guideline Based on Systematic Reviews:International Clinical Practice Guideline Based on Systematic Reviews

IMPORTANCE: Cerebral palsy (CP) is the most common childhood physical disability. Early intervention for children younger than 2 years with or at risk of CP is critical. Now that an evidence-based guideline for early accurate diagnosis of CP exists, there is a need to summarize effective, CP-specific early intervention and conduct new trials that harness plasticity to improve function and increase participation. Our recommendations apply primarily to children at high risk of CP or with a diagnosis of CP, aged 0 to 2 years. OBJECTIVE: To systematically review the best available evidence about CP-specific early interventions across 9 domains promoting motor function, cognitive skills, communication, eating and drinking, vision, sleep, managing muscle tone, musculoskeletal health, and parental support. EVIDENCE REVIEW: The literature was systematically searched for the best available evidence for intervention for children aged 0 to 2 years at high risk of or with CP. Databases included CINAHL, Cochrane, Embase, MEDLINE, PsycInfo, and Scopus. Systematic reviews and randomized clinical trials (RCTs) were appraised by A Measurement Tool to Assess Systematic Reviews (AMSTAR) or Cochrane Risk of Bias tools. Recommendations were formed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and reported according to the Appraisal of Guidelines, Research, and Evaluation (AGREE) II instrument. FINDINGS: Sixteen systematic reviews and 27 RCTs met inclusion criteria. Quality varied. Three best-practice principles were supported for the 9 domains: (1) immediate referral for intervention after a diagnosis of high risk of CP, (2) building parental capacity for attachment, and (3) parental goal-setting at the commencement of intervention. Twenty-eight recommendations (24 for and 4 against) specific to the 9 domains are supported with key evidence: motor function (4 recommendations), cognitive skills (2), communication (7), eating and drinking (2), vision (4), sleep (7), tone (1), musculoskeletal health (2), and parent support (5). CONCLUSIONS AND RELEVANCE: When a child meets the criteria of high risk of CP, intervention should start as soon as possible. Parents want an early diagnosis and treatment and support implementation as soon as possible. Early intervention builds on a critical developmental time for plasticity of developing systems. Referrals for intervention across the 9 domains should be specific as per recommendations in this guideline

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

Progressive resistance exercise increases strength but does not improve objective measures of mobility in young people with cerebral palsy

QUESTION: Does progressive resistance training (PRT) improve mobility and muscle strength in young people with cerebral palsy (CP)? DESIGN: Randomised, controlled trial with concealed allocation and blinded outcome assessment. SETTING: Recruitment from a large metropolitan children's hospital and a CP register in Australia. PARTICIPANTS: Participants had spastic diplegia CP, were aged 14 years to 22 years, had a disability classified as level II or III on the Gross Motor Function Classification System. Exclusion criteria were participation in PRT in the previous six months, single-event multi-level surgery in the previous two years, or contractures more than 20° at the hips and knees. Randomisation of 49 participants allocated 24 to the PRT group and 25 to the control group. INTERVENTIONS: The intervention group participated in a twice-weekly, 12-week PRT program performed at community gymnasia. Training was completed alone or in pairs under the supervision of a physiotherapist. Each participant was prescribed four to six individualised exercises, which were targeted to address deficits that had been identified by instrumented gait analysis, supplemented by clinical assessment. Participants completed three sets of 10 to 12 repetitions of each exercise at an intensity of 60% to 80% of one repetition maximum (RM). The control group continued with their usual recreation and physiotherapy provided it did not include PRT. OUTCOME MEASURES: The primary outcome was the six-minute walk test at week 13 and at week 24. Secondary outcome measures assessed objective mobility-related function (self-selected walking speed, timed stairs test, Gross Motor Function Measure (GMFM-66) dimensions D and E, Gait Profile Score), participant-rated mobility (Functional Mobility Scale, Functional Assessment Questionnaire) and muscle performance (1-RM) of leg press and reverse leg press). RESULTS: Forty-eight participants completed the study. After 12 weeks of training, there was no difference between the groups for the six-minute walk (0.1 m, 95% CI -20.6 to 20.9), stairs test (-0.9 s, 95% CI -4.7 to 2.9), GMFM dimension D (-1.3%, 95% CI -4.8 to 2.4) and E (0.9%, 95% CI -3.0 to 4.7), and reverse leg press 1-RM (-0.7 kg, 95% CI -4.3 to 2.8). The intervention group showed significant improvement in the Functional Mobility Scale at 5 m (0.6 units, 95% CI 0.1 to 1.1), the Functional Assessment Questionnaire (0.8 units, 95% CI 0.1 to 1.6) and leg press 1-RM (14.8 kg, 95% CI 4.3 to 25.3), compared with the control group. At week 24, there were no differences between the groups for any outcome. The groups did not significantly differ for the remaining secondary outcomes at either time-point. CONCLUSION: Individualised PRT increases strength in young people with CP. The participants thought their mobility had improved, although objectively it had not

Novel methods to enhance precision and reliability in muscle synergy identification during walking

Muscle synergies are hypothesized to reflect modular control of muscle groups via descending commands sent through multiple neural pathways. Recently, the number of synergies has been reported as a functionally relevant indicator of motor control complexity in individuals with neurological movement disorders. Yet the number of synergies extracted during a given activity, e.g. gait, varies within and across studies, even for unimpaired individuals. With no standardized methods for precise determination, this variability remains unexplained making comparisons across studies and cohorts difficult. Here, we utilize k-means clustering and intra-class and between-level correlation coefficients to precisely discriminate reliable from unreliable synergies. EMG was recorded bilaterally from eight leg muscles during treadmill walking at self-selected speed. Muscle synergies were extracted from 20 consecutive gait cycles using non-negative matrix factorization. We demonstrate that the number of synergies is highly dependent on the threshold when using the variance accounted for by reconstructed EMG. In contrast, our method utilized a quantitative metric to reliably identify four or five synergies underpinning walking in unimpaired adults and revealed synergies having poor reproducibility that should not be considered as true synergies. We show that robust and unreliable synergies emerge similarly, emphasizing the need for careful analysis in those with pathology