Genetic investigations in cerebral palsy.

The original description of cerebral palsy (CP) contained case histories suggesting that perinatal environmental stressors resulted in brain injury and neurodevelopmental disability. While there are clear associations between environmental impact on brain development and CP, recent studies indicate an 11% to 40% incidence of monogenic conditions in patients given a diagnosis of CP. A genetic diagnosis supports the delivery of personalized medicine. In this review, we describe how the Wnt pathway exemplifies our understanding of pathophysiology related to a gene variant (CTNNB1) found in some children diagnosed with CP. We cover studies undertaken to establish the baseline prevalence of monogenic conditions in populations attending CP clinics. We list factors indicating increased likelihood of a genomic diagnosis; and we highlight the need for a comprehensive, accurate, genotype-phenotype reference data set to aid variant interpretation in CP cohorts. We also consider the wider societal implications of genomic management of CP including significance of the diagnostic label, benefits and pitfalls of a genetic diagnosis, logistics, and cost.

Evaluation of the Training in Early Detection for Early Intervention (TEDEI) e-learning course using Kirkpatrick's method.

BACKGROUND: Early intervention in cerebral palsy could improve motor outcome but is only possible following early identification of those affected. There is a need for training of healthcare professionals (HCPs) in early detection of atypical motor development. We developed a video-based e-learning course - Training in Early Detection for Early Intervention (TEDEI) - to address this need. We evaluated whether participation in the course improved knowledge and changed behaviour of HCPs. METHODS: Participants were 332 HCPs (38% physiotherapists, 35.8% occupational therapists), predominantly UK-based (83.7%). Analysis of training effects used mixed methods and followed Kirkpatrick's model, first assessing "Reaction" through a feedback questionnaire involving Likert scale and free text responses (n = 141). "Learning" was assessed through multiple choice questions (MCQs): all 332 HCPs completed a pre-course quiz of 6 MCQs followed by the course, then a 16 item post-course quiz including the 6 pre-course questions. "Behaviour" was assessed through in-depth qualitative interviewing of 23 participants. RESULTS: "Reaction": TEDEI was found to be effective, engaging and well structured. "Learning": Scores improved significantly between the pre-course and post-course quiz, median improvement 1/6 (z = 5.30, p < 0.001). HCPs also reported a perceived improvement in their knowledge, confidence and ability. "Behaviour": HCPs could see how TEDEI would improve their clinical practice through having an assessment framework, ways of working better with parents, and developing observational skills useful for tele-health assessments. CONCLUSION: Our brief e-learning course on early detection for early intervention was viewed positively, improved knowledge and showed potential for positive changes in practice. Kirkpatrick's model provided a useful framework for undertaking this evaluation.

Parental engagement in early intervention for infants with cerebral palsy-A realist synthesis.

BACKGROUND: Emphasis on parental engagement strategies within occupational therapy and physiotherapy early intervention (EI) programmes for infants at high risk of cerebral palsy (CP) has increased. This reflects consensus that increasing parent participation enhances treatment efficacy, potentially improving infant and parent outcomes. However, evaluation of parental engagement in EI is complex. Despite the growing application of parental engagement strategies, aligned with family-centred care practice, theoretical evaluation is currently lacking within the literature. This realist synthesis aimed to identify component theories underlying EI strategies to support parental engagement and to use empirical findings to evaluate how these work in practice. METHODS: Realist synthesis: Databases Medline, Embase, Amed, CINAHL and PsychInfo were searched (from February 1985 - February 2020); further articles were sourced from reference lists. A data extraction form was used, and a Critical Appraisal Skills Programme tool was used to assess study rigour. RESULTS: Twenty-six articles were included. Quality of relationships, parent education and intervention co-design were the key themes related to parental engagement strategies. Findings indicate that constructive parent reasoning mechanisms of trust, belief, sense of control, perceived feasibility of home programme delivery and ultimately motivation are linked to the underlying intervention resources afforded by specific strategies (e.g., coaching pedagogy). These responses are precursors to engagement outcomes that include increased parental self-efficacy and adherence. Importantly, parental self-efficacy can initiate a process of change leading to improved parental confidence and anxiety. CONCLUSIONS: Sensitively designed programme strategies, centred on relational quality between parent, infant and therapist, are fundamental for effective parent connection, involvement and investment within EI for infants with CP.

Tyneside Pegboard Test for unimanual and bimanual dexterity in unilateral cerebral palsy: association with sensorimotor impairment.

AIM: We explored the psychometric properties of the recently developed Tyneside Pegboard Test (TPT) for unimanual and bimanual dexterity in children with unilateral cerebral palsy (CP) and investigated the impact of sensorimotor impairments on manual dexterity. METHOD: In this cross-sectional study, the TPT was assessed in 49 children with unilateral CP (mean age 9y 8mo, SD 1y 11mo, range 6-15y; 30 males, 19 females; 23 with right unilateral CP). All participants additionally underwent a standardized upper limb evaluation at body function and activity level. We investigated: (1) known-group, concurrent, and construct validity and (2) impact of sensorimotor impairments including spasticity, grip force, stereognosis, and mirror movements using analysis of covariance, Spearman's rank correlation (r), and multiple linear regression (R2 ) respectively. RESULTS: TPT outcomes significantly differed according to the Manual Ability Classification System (p<0.001, known-group validity). Relationships were found between the unimanual TPT tasks and the Jebsen-Taylor Hand Function Test (r=0.86-0.88, concurrent validity). Bimanual TPT tasks were negatively correlated with the Assisting Hand Assessment, ABILHAND-Kids, and Children's Hand-use Experience Questionnaire (r=-0.38 to -0.78, construct validity). Stereognosis was the main determinant influencing all tasks (p<0.001, R2 =37-50%). Unimanual dexterity was additionally determined by grip strength (p<0.05, R2 =8-9%) and mirror movements in the more impaired hand (p<0.05, R2 =4-8%). Bimanual dexterity was also explained by mirror movements in the more impaired hand (p<0.01, R2 =10-16%) and spasticity (p=0.04, R2 =5%). INTERPRETATION: The TPT is a valid test to measure unimanual and bimanual dexterity in unilateral CP. The results further emphasize the importance of somatosensory impairments in children with unilateral CP. What this paper adds The Tyneside Pegboard Test is valid for measuring unimanual and bimanual dexterity in unilateral cerebral palsy. Children with poorer manual ability show worse unimanual and bimanual dexterity. Stereognosis is the main predictor of both unimanual and bimanual dexterity. Stronger mirror movements in the more impaired hand result in worse bimanual dexterity.

Early intervention programmes for infants at high risk of atypical neurodevelopmental outcome.

The purpose of this review is to present a new framework, EI SMART (early intervention: sensorimotor development, attention and regulation, relationships, and therapist support) for identifying key components that could contribute to more effective interventions for infants at high risk of atypical neurodevelopmental outcome. We present a clinical consensus of current challenges and themes in early intervention, based on multidisciplinary group discussions, including parents of high-risk infants, supported by a literature review. Components to include in early intervention programmes are: (1) promotion of self-initiated, developmentally appropriate motor activity; (2) supporting infant self-regulation and the development of positive parent-infant relationships; and (3) promotion of early communication skills, parent coaching, responsive parenting, and supporting parental mental well-being. Such multimodal programmes may need to be evaluated as a package. WHAT THIS PAPER ADDS: Early intervention programmes should address sensorimotor development, attention, self-regulation, and early communication skills. Therapist input to the programme should include parent coaching and support for parental mental well-being.

PROGRAMAS DE INTERVENCIÓN TEMPRANA PARA LACTANTES CON ALTO RIESGO DE TRATARNOS DEL DESARROLLO NEUROLÓGICO: El propósito de esta revisión es presentar un nuevo marco, EI SMART (intervención temprana: desarrollo sensoriomotor, atención y regulación, relaciones y apoyo del terapeuta) para identificar componentes clave que podrían contribuir a intervenciones más efectivas para los bebés con alto riesgo de desarrollar un trastorno del neurodesarrollo. Presentamos un consenso clínico de los desafíos y temas actuales en la intervención temprana, basados ​​en discusiones grupales multidisciplinares, incluidos los padres de bebés con alto riesgo, respaldados por una revisión de la literatura. Los componentes para incluir en los programas de intervención temprana son (1) la promoción de actividades motoras autoiniciadas y apropiadas para el desarrollo; (2) apoyar la autorregulación infantil y el desarrollo de relaciones positivas entre padres e infantes; (3) promoción de las habilidades de comunicación temprana, entrenamiento de padres, crianza responsable y apoyo al bienestar mental de los padres. Es posible que dichos programas multimodales deban evaluarse como un paquete terapéutico.

PROGRAMAS DE INTERVENÇÃO PRECOCE PARA CRIANÇAS EM ALTO RISCO DE RESULTADO ANORMAL DO DESENVOLVIMENTO: O propósito desta revisão é apresentar um novo formato: EI SMART (intervenção precoce: desenvolvimento sensóriomotor, atenção e regulação, relacionamentos, e apoio do terapeuta) para identificar componentes centrais que podem contribuir para intervenções mais efetivas em lactentes de alto risco. Apresentamos um consenso clínico dos desafios correntes e temas em intervenção precoce, com base em discussões interdisciplinares, incluindo pais de lactentes de alto risco, com apoio de uma revisão de literatura. Os componentes a serem incluídos em programas de intervenção precoce são 1) promoção de atividade motora auto-iniciada apropriada para o desenvolvimento; 2) suporte para a auto-regulação do lactente e desenvolvimento de relações pais-filhos positivas; 3) promoção de habilidades precoces de comunicação, suporte aos pais, parentalidade responsável, e suporte ao bem estar mental dos pais. Tais programas multimodais podem precisar ser avaliados em forma de um pacote.

Feasibility of parent communication training with remote coaching using smartphone apps.

BACKGROUND: Communication training for parents of young children with neurodisability is often delivered in groups and includes video coaching. Group teaching is problematic when there is wide variation in the characteristics and needs amongst participants. AIMS: To assess the potential feasibility and acceptability of delivering one-to-one parent training supported by remote coaching using smartphone apps and of conducting further trials of the intervention. METHODS & PROCEDURES: We aimed to recruit eight children aged 12-48 months with motor disorders and communication difficulties and to provide families with individual parent training in six weekly home visits supplemented by remote coaching via smartphone apps. For outcome measurement, parents recorded their interaction with their child thrice weekly during baseline (3 weeks), intervention, post-intervention (3 weeks) and follow-up (1 week). Measures comprised parent responsiveness and counts of children's communication and vocalization. Research design feasibility was measured through rates of recruitment, attrition, outcome measure completion and agreement between raters on outcome measurement. Intervention feasibility was assessed through the proportion of therapy sessions received, the number of videos and text messages shared using the apps in remote coaching, and message content. Parents were interviewed about the acceptability of the intervention and trial design. Interviews were transcribed and analyzed using inductive thematic analysis. OUTCOMES & RESULTS: Nine children were recruited over 16 weeks. All fitted the inclusion criteria. Four families withdrew from the study. Five families completed the intervention. No family submitted the target number of video recordings for outcome measurement. Interrater agreement was moderate for child communication (K = 0.46) and vocalization (K = 0.60) and high for The Responsive Augmentative and Alternative Communication Style scale (RAACS) (rs = 0.96). Parents who completed the intervention reported positive experiences of the programme and remote coaching via the apps. Therapist messages via the app contained comments on parent and child behaviour and requests for parental reflection/action; parental messages contained reflections on children's communication. CONCLUSIONS & IMPLICATIONS: The intervention and study design demanded high levels of parental involvement and was not suitable for all families. Recording shorter periods of interaction via mobile phones or using alternative methods of data collection may increase feasibility of outcome measurement.

Understanding frames: A qualitative exploration of standing frame use for young people with cerebral palsy in educational settings.

BACKGROUND: Consensus opinion supports standing frame use as part of postural management for nonambulant young people with cerebral palsy. Most young people with cerebral palsy in the United Kingdom, who use standing frames, use them at nursery or school, rather than at home. In this paper we report professionals' and parents' experiences and views of standing frame use specifically in educational settings. This research was conducted as part of a large mixed methods study to determine the acceptability and inform the design of a future trial of standing frames. METHODS: Qualitative methods were used: focus groups with educational professionals, parents and clinicians (paediatricians, physiotherapists and occupational therapists) were convened. Data were analysed thematically using framework analysis. RESULTS: Five focus groups were conducted. The overarching theme "flexibility" encompassed four subordinate themes: (i) "balancing education and therapy," which described the way education professionals had to juggle different priorities from health professionals within a multi-disciplinary team; (ii) "young people's autonomy," which highlighted participants' belief that standing frame use should be centred on the individual young person and their needs; (iii) "working within logistical boundaries," which demonstrated that "ideal" standing frame use was not always possible due to logistical issues (e.g., staffing and standing frame availability); and (iv) "competence and confidence," which highlighted that educational professionals felt that they lacked the training to confidently position young people in their standing frame. CONCLUSIONS: This paper highlights the complexity of standing frame use in the educational setting. If a standing frame programme is prescribed to be delivered in an educational setting, strong multidisciplinary and interagency communication is essential to balance therapy versus education. Training is required to ensure staff are competent in using the standing frame with the young person understanding their individual requirements. A flexible approach-inclusive of the young person's needs, logistical demands and resource-is necessary.

Fifteen-minute consultation: Management of the upper limb in unilateral cerebral palsy.

Children with unilateral cerebral palsy (UCP) have complex health, education and social care needs. Delayed gross motor milestones are the most common presenting feature, and much of the early management focuses on gross motor skills and lower limb management. In later childhood, adolescence and adulthood, upper limb function has significant impact on activity, participation and independence. There is clear pathophysiological rationale and emerging clinical evidence that earlier intervention to improve upper limb function is beneficial. Whereas most children with UCP are managed in secondary care, it is recommended that the assessment and delivery of specialist intervention for the upper limb occurs at a regional centre.

Current Therapeutic Management of Perinatal Stroke with a Focus on the Upper Limb: A Cross-Sectional Survey of UK Physiotherapists and Occupational Therapists.

AIM: To determine current UK pediatric physiotherapist (PT) and occupational therapist (OT) management of perinatal stroke. DESIGN: Web-based cross-sectional survey. METHODS: Participants were members of the Association of Paediatric Chartered Physiotherapists and Occupational Therapists specialist section: children young people and families working with infants. Items covered prioritization of referrals, assessments, therapy approaches aimed at the upper limb, and parental support. RESULTS: 179 therapists responded. 87.2% of PTs and 63.0% of OTs managed infants with perinatal stroke. Infants with clinical signs of motor dysfunction at referral were prioritized for early initial assessment. The most frequently used assessments were the Alberta Infant Motor Scale (AIMS) and Bayley Scales of Infant Development (BSID). Of PTs and OTs, 41.9 and 40.0% used no standardized assessments. Frequently used therapy interventions were Bobath/Neurodevelopmental Therapy (NDT), positioning aids and passive movements. 88.1% of therapists would choose a bilateral rather than unilateral (affected side) therapy approach for infants with perinatal stroke aged up to 6 months. Of PTs and OTs, 56.9 and 57.1% provided psychological support to families. CONCLUSIONS: Assessment and provision of therapy services following perinatal stroke is variable. Increased use of standardized assessments and centralized data collection regarding service provision for high-risk infants is recommended.

Human neural stem cells dispersed in artificial ECM form cerebral organoids when grafted in vivo.

Human neural stem cells (hNSC) derived from induced pluripotent stem cells can be differentiated into neurons that could be used for transplantation to repair brain injury. In this study we dispersed such hNSC in a three-dimensional artificial extracellular matrix (aECM) and compared their differentiation in vitro and following grafting into the sensorimotor cortex (SMC) of postnatal day (P)14 rat pups lesioned by localised injection of endothelin-1 at P12. After 10-43 days of in vitro differentiation, a few cells remained as PAX6+ neuroprogenitors but many more resembled post-mitotic neurons expressing doublecortin, ß-tubulin and MAP2. These cells remained dispersed throughout the ECM, but with extended long processes for over 50 µm. In vivo, by 1 month post grafting, cells expressing human specific markers instead organised into cerebral organoids: columns of tightly packed PAX6 co-expressing progenitor cells arranged around small tubular lumen in rosettes, with a looser network of cells with processes around the outside co-expressing markers of immature neurons including doublecortin, and CTIP2 characteristic of corticofugal neurons. Host cells also invaded the graft including microglia, astrocytes and endothelial cells forming blood vessels. By 10 weeks post-grafting, the organoids had disappeared and the aECM had started to break down with fewer transplanted cells remaining. In vitro, cerebral organoids form in rotating incubators that force oxygen and nutrients to the centre of the structures. We have shown that cerebral organoids can form in vivo; intrinsic factors may direct their organisation including infiltration by host blood vessels.

Feasibility trial of an early therapy in perinatal stroke (eTIPS).

BACKGROUND: Perinatal stroke (PS) affects up to 1/2300 infants and frequently leads to unilateral cerebral palsy (UCP). Preterm-born infants affected by unilateral haemorrhagic parenchymal infarction (HPI) are also at risk of UCP. To date no standardised early therapy approach exists, yet early intervention could be highly effective, by positively influencing processes of activity-dependent plasticity within the developing nervous system including the corticospinal tract. Our aim was to test feasibility and acceptability of an "early Therapy In Perinatal Stroke" (eTIPS) intervention, aiming ultimately to improve motor outcome. METHODS: Design: Feasibility trial, North-East England, August 2015-September 2017. Participants were infants with PS or HPI, their carers and therapists. The intervention consisted of a parent-delivered lateralised therapy approach starting from term equivalent age and continuing until 6 months corrected age. The outcome measures were feasibility (recruitment and retention rates) and acceptability of the intervention (parental questionnaires including the Warwick-Edinburgh Mental Wellbeing Scale (WEBWMS), qualitative observations and in-depth interviews with parents and therapists). We also reviewed clinical imaging data and undertook assessments of motor function, including the Hand Assessment for Infants (HAI). Assessments were also piloted in typically developing (TD) infants, to provide further information on their ease of use and acceptability. RESULTS: Over a period of 18 months we screened 20 infants referred as PS/HPI: 14 met the inclusion criteria and 13 took part. At 6 months, 11 (85%) of those enrolled had completed the final assessment. Parents valued the intervention and found it acceptable and workable. There were no adverse events related to the intervention. We recruited 14 TD infants, one of whom died prior to undertaking any assessments and one of whom was subsequently found to have a condition affecting neurodevelopmental progress: thus, data for 12 TD infants was analysed to 6 months. The HAI was well tolerated by infants and highly valued by parents. Completion rates for the WEBWMS were high and did not suggest any adverse effect of engagement in eTIPS on parental mental wellbeing. CONCLUSION: The eTIPS intervention was feasible to deliver and acceptable to families. We plan to investigate efficacy in a multicentre randomised controlled trial. TRIAL REGISTRATION: ISRCTN12547427 (registration request submitted 28/05/2015; retrospectively registered, 30/09/2015).

The Tyneside Pegboard Test: development, validation, and observations in unilateral cerebral palsy.

AIM: The aims of this study were twofold: first, to develop and validate a timed test of unimanual and bimanual dexterity suitable for those with disability affecting hand function; second, to explore relationships between unimanual and bimanual completion times. METHOD: We developed the Tyneside Pegboard Test (TPT), an electronically timed test with three peg sizes, incorporating an asymmetrical bimanual task. Nine hundred and seventy-four participants (455 males, 519 females; age range 4-80y) provided normative data. Test-retest reliability and construct validity were assessed (50 adults: 14 males, 36 females; 15-73y) on two occasions 2 weeks apart. Bimanual and unimanual completion times were measured in 87 children (51 males, 36 females) with unilateral cerebral palsy (CP) and 498 individuals in a comparison group (238 males, 260 females; 5-15y). RESULTS: The comparison group showed an asymmetrical U-shaped relationship between completion times and age. Intraclass correlation coefficients ranged from 0.74 to 0.91, indicating moderate test-retest reliability. There was a negative relationship between average TPT bimanual times and Purdue pegboard bimanual scores (Spearman's rho -0.611, degrees of freedom 44, p<0.001). Children with unilateral CP had greater prolongation of bimanual than unimanual completion times compared with the comparison group (mean difference 20.31s, 95% confidence interval 18.13-22.49, p<0.001). INTERPRETATION: The TPT is accessible for those with impaired hand function. Children with unilateral CP demonstrated disproportionate bimanual deficits, even allowing for unimanual dexterity: this has implications for therapy. WHAT THIS PAPER ADDS: We developed an adapted, electronically timed 9-hole pegboard test. Our modifications facilitate use by those with disability affecting hand function. The test incorporates an asymmetrical bimanual task. Children with unilateral cerebral palsy showed disproportionate bimanual dexterity deficits even allowing for unimanual dexterity.

Determinants of parent-delivered therapy interventions in children with cerebral palsy: A qualitative synthesis and checklist.

INTRODUCTION: Parent-delivered therapy interventions for children with cerebral palsy can help achieve a sufficient therapy dose, improve parental mental well-being, and facilitate parent-child relationships creating a more relaxed familial environment. However, parent-delivered interventions may also lead to increased parental stress, guilt if the therapy is not delivered, and time constraints. The primary aim of this review was to gain a deeper understanding of the determinants of effective parent-delivered therapy interventions. METHOD: Searches were conducted in the following databases: Medline, PubMed, Scopus, Embase, CINAHL, and Cochrane. Studies had to meet the following inclusion criteria: descriptions of parent/health care professional/child experiences of parent-delivered therapy interventions for children and young people age 0-18 years with cerebral palsy, published in the English language between January 1989 and May 2017, with qualitative or mixed methods research design. The articles were critically appraised, then synthesized using a meta-ethnographic approach. RESULTS: A literature search identified 17 articles, which met the inclusion criteria. Three main themes were identified: (a) building trusting relationships, (b) enabling the parents to cope, and (c) for parents and health care professionals to see the intervention as a priority. Further synthesis presented three concepts identifying the important aspects of the interventions: empowerment, motivation, and relationships. CONCLUSIONS: The themes and concepts emerging from this qualitative synthesis can be addressed by specific points of action to support parent-delivered therapy interventions. We have summarized these in a checklist for use by intervention developers, health care professionals, and parents.

Participatory design in the development of an early therapy intervention for perinatal stroke.

BACKGROUND: Perinatal stroke is the leading cause of unilateral (hemiparetic) cerebral palsy, with life-long personal, social and financial consequences. Translational research findings indicate that early therapy intervention has the potential for significant improvements in long-term outcome in terms of motor function. By involving families and health professionals in the development and design stage, we aimed to produce a therapy intervention which they would engage with. METHODS: Nine parents of children with hemiparesis and fourteen health professionals involved in the care of infants with perinatal stroke took part in peer review and focus groups to discuss evolving therapy materials, with revisions made iteratively. The materials and approach were also discussed at a meeting of the London Child Stroke Research Reference Group. Focus group data were coded using Normalisation Process Theory constructs to explore potential barriers and facilitators to routine uptake of the intervention. RESULTS: We developed the Early Therapy in Perinatal Stroke (eTIPS) program - a parent-delivered, home-based complex intervention addressing a current gap in practice for infants in the first 6 months of life after unilateral perinatal stroke and with the aim of improving motor outcome. Parents and health professionals saw the intervention as different from usual practice, and valuable (high coherence). They were keen to engage (high cognitive participation). They considered the tasks for parents to be achievable (high collective action). They demonstrated trust in the approach and felt that parents would undertake the recommended activities (high collective action). They saw the approach as flexible and adaptable (high reflexive monitoring). Following suggestions made, we added a section on involving the extended family, and obtained funding for a website and videos to supplement written materials. CONCLUSIONS: Focus groups with parents and health professionals provided meaningful feedback to iteratively improve the intervention materials prior to embarking on a pilot study. The intervention has a high potential to normalize and become a routine part of parents' interactions with their child following unilateral perinatal stroke.