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Cerebral palsy (CP) is a nonprogressive neurological disorder and the most common physical disability of childhood. There is no cure for CP, but stem cells have the potential to improve brain injury and hence function. This phase 1 clinical trial investigated the safety of the intravenous infusion of full-matched sibling cord blood cells for children with CP aged 1 to 16 years. Preliminary efficacy outcomes were also investigated. Twelve participants received 12/12 HLA-matched sibling cord blood cell infusions. One treatable serious adverse reaction to cryoprotectant was observed, and no adverse reactions occurred beyond 24 h after infusion. Gross motor function measure (GMFM-66) scores did not improve compared with baseline beyond what could be expected from developmental levels, and participants had varied changes in the Quality of Upper Extremity Skills Test (QUEST) and Vineland Adaptive Behavior Scales (VABS-II) scores. In conclusion, matched sibling cord blood cell infusion for children with CP is relatively safe when conducted in an appropriate facility. Australian and New Zealand Clinical Trials Registry (ACTRN12616000403437) and Clinicaltrials.gov (NCT03087110).

PURPOSE. The purpose of this executive summary is to review the process and outcomes of the Academy of Pediatric Physical Therapy Research Summit V, “Optimizing transitions from infancy to young adulthood in children with neuromotor disabilities: biological and environmental factors to support functional independence.” SUMMARY OF KEY POINTS. An interdisciplinary group of researchers, representatives from funding agencies, and individuals with neuromotor disabilities and their parents participated in an intensive 2.5-day summit to determine research priorities to optimize life transitions for children with neuromotor disabilities. Recommended priorities for research included: (1) Promoting self-determination and self-efficacy of individuals with neuromotor disabilities and their families, (2) Best care at the right time: evidence-based best practice care, led and navigated by families seamlessly across the lifespan, (3) Strengthening connections between developmental domains to enhance function and participation, and (4) Optimal dosing and timing to support adaptive bone, muscle, and brain plasticity across the lifespan.

Background aims Umbilical cord blood (UCB) infusion is being investigated as a treatment for a range of neurological conditions, primarily because of its potent immunomodulatory effects mediated via paracrine signaling. Although initial research mainly utilized autologous UCB, allogeneic samples from a sibling or unrelated donor have now become more common. With the use of allogeneic UCB, questions have arisen surrounding the necessity for human leukocyte antigen (HLA) matching, preparative regimens and immunosuppressant drugs. To investigate the safety of allogeneic UCB for the treatment of neurological conditions and the impact of HLA mismatching and immunosuppresion, the authors conducted a systematic review of the safety of allogeneic UCB infusion for neurological conditions. Methods A systematic review of published and gray literature was conducted to investigate the safety of allogeneic UCB infusions for neurological conditions. Results Authors identified 10 studies using allogeneic UCB to treat autism spectrum disorder, cerebral palsy, stroke, traumatic brain injury and various other conditions. A total of 361 participants (with at least 442 UCB infusions) received a range of HLA-matched/untyped allogeneic units and cell doses, with the majority not administered post-infusion immunosuppression. There were no reported serious adverse events definitely or probably related to the allogeneic UCB infusion, nor later potential complications such as graft-versus-host disease or teratoma formation. Conclusions Although variability between studies is high, the available data do not identify safety concerns with allogeneic UCB infusion for the treatment of neurological conditions, even with variable HLA matching or no immunosuppression.

IntroductionCerebral palsy (CP) is the most common childhood physical disability. Accurate diagnosis before 6 months is possible using predictive tools and decision-making skills. Yet diagnosis is typically made at 12–24 months of age, hindering access to early interventions that improve functional outcomes. Change in practice is required for physicians in key diagnostic behaviours. This study aims to close the identified research–practice gap and increase accurate CP diagnosis before 6 months of age through tailored web-based implementation interventions. This trial will determine whether adaptive e-learning using virtual patients, targeting CP diagnostic behaviours and clinical decision-making skills, effectively changes physician behaviour and practice compared with non-adaptive e-learning instructional design or control.Methods and analysisThis study is a 3-arm parallel superiority randomised controlled trial of two tailored e-learning interventions developed to expedite physician CP diagnosis. The trial will compare adaptive (arm 1) and non-adaptive (arm 2) instructional designs with waitlist control (arm 3) to evaluate change in physician behaviour, skills and diagnostic practice. A sample size of 275 paediatric physicians enables detection of small magnitude effects (0.2) of primary outcomes between intervention comparators with 90% power (α=0.05), allowing for 30% attrition. Barrier analysis, Delphi survey, Behaviour Change Wheel and learning theory frameworks guided the intervention designs. Adaptive and non-adaptive video and navigation sequences utilising virtual patients and clinical practice guideline content were developed, integrating formative key features assessment targeting clinical decision-making skills relative to CP diagnosis.Physician outcomes will be evaluated based on postintervention key feature examination scores plus preintervention/postintervention behavioural intentions and practice measures. Associations with CP population registers will evaluate real-world diagnostic patient outcomes. Intervention costs will be reported in a cost–consequence analysis from funders’ and societal perspectives.Ethics and disseminationEthics approved from The University of Sydney (Project number 2021/386). Results will be disseminated through peer-reviewed journals and scientific conferences.Trial registration numberAustralian New Zealand Clinical Trials Registry: ACTRN 12622000184774.

AIM: To provide recommendations for interventions to improve physical function for children and young people with cerebral palsy. METHOD: An expert panel prioritized questions and patient-important outcomes. Using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods, the panel assessed the certainty of evidence and made recommendations, with international expert and consumer consultation. RESULTS: The guideline comprises 13 recommendations (informed by three systematic reviews, 30 randomized trials, and five before-after studies). To achieve functional goals, it is recommended that intervention includes client-chosen goals, whole-task practice within real-life settings, support to empower families, and a team approach. Age, ability, and child/family preferences need to be considered. To improve walking ability, overground walking is recommended and can be supplemented with treadmill training. Various approaches can facilitate hand use goals: bimanual therapy, constraint-induced movement therapy, goal-directed training, and cognitive approaches. For self-care, whole-task practice combined with assistive devices can increase independence and reduce caregiver burden. Participation in leisure goals can combine whole-task practice with strategies to address environmental, personal, and social barriers. INTERPRETATION: Intervention to improve function for children and young people with cerebral palsy needs to include client-chosen goals and whole-task practice of goals. Clinicians should consider child/family preferences, age, and ability when selecting specific interventions.

In the field of disability research and advocacy, the notion of 'cures' is contentious. Cerebral palsy (CP) is no exception. In this narrative review, we combine perspectives gained during community consultation undertaken for the Australian and New Zealand Cerebral Palsy Strategy, 2020 with those published in the scientific and grey literature to understand whether 'cures for CP' is a reasonable and appropriate goal. We frame these perspectives through the lens of several ethical principles central to the discussion. These include maintaining hope while also being realistic, sensitivity to sharply different viewpoints amongst people with disability and their families, and responding to community priorities, societal attitudes, and identity. Through this exploration of the literature and perspectives, we arrived at a definition of 'cures for CP' that is pluralized and focuses on functional improvement and/or symptom reduction whilst still acknowledging the potential for neural repair/regeneration strategies.

Background Cerebral palsy (CP) is the most common motor disability of childhood. Its early identification is an important priority for parents and is critical for access to early intervention resources, which may optimize function. Methods A prospective cohort of term neonates at high risk for CP was assessed by neonatal magnetic resonance imaging (MRI) to determine myelination of the posterior limb of the internal capsule, General Movements Assessment to assess typical fidgety movements at age three months, and followed to at least age two years to determine diagnosis of CP based on neurological examination. Results Seven of 58 children developed CP (12%), two with moderate/severe CP. Sensitivity and specificity for abnormal myelination of the posterior limb of the internal capsule were (PLIC) was 29% and 94%, and for absent fidgety movements, 29% and 98%, respectively. Negative predictive value of both absent myelination of the PLIC and absent fidgety movements was 90% (79% to 96%) for any CP and 98% (90% to 100%) for moderate/severe CP cerebral palsy. None of the children with both normal PLIC and normal fidgety movements had moderate/severe CP. Conclusion Normal neonatal MRI and General Movements Assessment at age three months are reassuring that a high-risk term-born child is at low risk for moderate/severe CP. These results are important for counseling parents and individualizing therapy resources in the community.

Children with cerebral palsy (CP) are five times more likely than typically developing children to have sleep problems, resulting in adverse outcomes for both children and their families. The purpose of this systematic review was to gather current evidence regarding assessments and interventions for sleep in children under age 2 years with or at high risk for CP and integrate these findings with parent preferences.Five databases (CINAHL, EMBASE, OVID/Medline, SCOPUS, and PsycINFO) were searched. Included articles were screened using preferred reporting items for systematic reviews and meta-analyses guidelines, and quality of the evidence was reviewed using best evidence tools by two independent reviewers at minimum. An online survey was conducted regarding parent preferences through social media channels.Eleven articles met inclusion criteria. Polysomnography emerged as the only high-quality assessment for the population. Three interventions (medical cannabis, surgical interventions, and auditory, tactile, visual, and vestibular stimulations) were identified; however, each only had one study of effectiveness. The quality of evidence for polysomnography was moderate, while the quality and quantity of the evidence regarding interventions was low. Survey respondents indicated that sleep assessments and interventions are highly valued, with caregiver-provided interventions ranked as the most preferable.Further research is needed to validate affordable and feasible sleep assessments compared to polysomnography as the reference standard. In the absence of diagnosis-specific evidence of safety and efficacy of sleep interventions specific to young children with CP, it is conditionally recommended that clinicians follow guidelines for safe sleep interventions for typically developing children.

Aims Historically, the diagnosis of cerebral palsy has been made after 12 months of age, delaying access to crucial early intervention that optimises functional outcomes. This study aimed to identify and specify priority physician diagnostic behaviours to target in implementation interventions to increase the rate of diagnosis of cerebral palsy under 6 months of age in Australia. Methods We conducted a two-round online Delphi study with a multi-professional expert panel of cerebral palsy researchers and clinicians. A reference group identified a six-item list of potential diagnostic behaviours, which were modifiable at the individual level, that could lead to an early cerebral palsy diagnosis. In the first survey, participants rated the importance of each item on a 10-point Likert scale and supplied their reasoning for this, and were able to suggest new behaviours. In the second survey, participants ranked items in order of priority. Results All six items reached consensus for inclusion (100%). No new items were added to the list. Ranking identified the top three priorities for online physician implementation interventions: (i) refer for or conduct the General Movements Assessment; (ii) refer for or conduct the Hammersmith Infant Neurological Examination; and (iii) communication of the diagnosis. Conclusion An online Delphi method can effectively inform tailored implementation intervention development. A consensus was achieved on the priority physician diagnostic behaviours to target in interventions to lower the age of cerebral palsy diagnosis in Australia.

Aim We previously reported sensitivity and specificity levels of the general movements assessment (GMA) to detect cerebral palsy (CP) at 1 year within a clinical setting and with the assistance of the New South Wales (NSW) Rater Network. The aim of this study was to determine whether similarly high levels of validity could be maintained in the same group at 2 years. Methods A prospective longitudinal cross-sectional study was conducted. GMA was blind-rated from conventional video by two independent certified raters, blinded to medical history. A third rater resolved disagreements. High-risk population screening for CP using the GMA during the fidgety period (12-20 weeks) was carried out in four neonatal intensive care units and one CP service over a 30-month period. Participants were 259 high-risk infants for the initial study. Multidisciplinary follow-up at 2-3 years included Bayley Scales of Infant Development and confirmed diagnosis of CP. Sensitivity and specificity values were calculated with true positives defined as a confirmed diagnosis of CP. Results At 2-3 years, 184 (71%) completed the follow-up assessment. GMA was normal for 134 (73%, low risk for CP), absent fidgety for 48 (26%, high risk for CP) and abnormal fidgety for 2 (1%, high risk for abnormal neurological disorder). Sensitivity for detecting CP was 97.6% (40/41) and specificity 95.7% (133/139). Sensitivity for detecting any abnormal outcome with absent/abnormal fidgety general movements (GMs) was 57.9% (44/76) and specificity 94.4% (101/107). Conclusion Excellent levels of sensitivity and specificity of the GMA for detecting CP in the clinical setting were maintained at 2 years and were similar to our previously reported findings.

Purpose: To investigate the effect of a knowledge translation intervention on knowledge and frequency of routine evidence-based assessment behaviours of healthcare professionals working with children with cerebral palsy. Methods: A before-and-after longitudinal study was conducted in five disability organisations. Four organisations (Commencing Knowledge Translation group) implemented a multifaceted intervention: knowledge brokers, targeted education, electronic-evidence library, and clinical outcomes database. These strategies were already in place at the fifth organisation (Comparison group). Outcomes evaluated at 0, 6, 12, and 24 months were health-professional knowledge and routine assessment behaviours (self-report and “completeness” of clinical assessment). Generalised estimating equations determined longitudinal changes. Results: Four hundred and forty-seven professionals involved 861 children in the study. The Comparison group had higher knowledge and routine assessment behaviours at baseline. Professional knowledge in both groups remained stable (differences in change from baseline to 24 months: 0.3 units, 95%CI: −0.76 to 1.36). Assessment completeness of the Comparison group was stable (baseline mean 68 units, 95%CI: 65–71); the Commencing Knowledge Translation group improved from baseline mean 35 units (95%CI: 33–36), peaking at 12 months (mean 68 (95%CI: 65–71). Conclusions: Multifaceted organisational support improved health-professional routine evidence-based assessment behaviours with children with cerebral palsy, despite no change in knowledge. Trial registration: This trial was not a controlled health care intervention and was registered retrospectively: ACTRN12616001616460. The protocol of the trial was published in 2015 as follows: Imms et al. [6]. Implications for rehabilitation • A multifaceted knowledge translation intervention increased allied health professionals’ assessment behaviours. • Knowledge translation strategies can be chosen to target change in knowledge and/or change in behaviour. • Knowledge translation interventions should be designed to address organisational barriers and enhance organisational supports. • Interventions that target healthcare professionals’ behaviour directly can be effective even if their knowledge does not change.

To examine the association between brain magnetic resonance imaging (MRI) characteristics and executive function and bimanual performance in children with unilateral cerebral palsy (CP).Clinical MRI brain scans were classified as: (1) predominant pathological pattern (normal, white matter injury [WMI]; grey matter injury; focal vascular insults [FVI]; malformations; or miscellaneous); and (2) focal lesions (frontal, basal ganglia, and/or thalamus). Assessments included: (1) bimanual performance; (2) unimanual dexterity; and (3) executive function tasks (information processing, attention control, cognitive flexibility, and goal setting) and behavioural ratings (parent).From 131 recruited children, 60 were ineligible for analysis, leaving 71 children (47 males, 24 females) in the final sample (mean age 9y [SD 2y], 6y-12y 8mo). Brain MRIs were WMI (69%) and FVI (31%); and frontal (59%), thalamic (45%), basal ganglia (37%), and basal ganglia plus thalamic (21%). Bimanual performance was lower in FVI versus WMI (p0.003), and with frontal (p=0.36), basal ganglia (p=0.032), and thalamic/basal ganglia lesions (p=0.013). Other than information processing, executive function tasks were not associated with predominant pattern. Frontal lesions predicted attention control (p=0.049) and cognitive flexibility (p=0.009) but not goal setting, information processing, or behavioural ratings.Clinical brain MRI predicts cognitive and motor outcomes when focal lesions and predominate lesion patterns are considered. What this paper adds Early brain magnetic resonance imaging (MRI) predicts bimanual performance and cognitive outcomes. Brain MRI may identify children requiring targeted interventions. Basal ganglia with/without thalamic lesions predicted bimanual performance. Frontal lesions were associated with attention control and cognitive flexibility. Brain MRI predominant patterns predicted motor, not cognitive outcomes, other than information processing.La resonancia magnética cerebral es un predictor del rendimiento bimanual y la función ejecutiva en niños con parálisis cerebral unilateral OBJETIVO: Examinar la asociación entre las características de la resonancia magnética cerebral (RMN) y la función ejecutiva y el rendimiento bimanual en niños con parálisis cerebral unilateral (PC). MÉTODO: Los escáneres cerebrales de resonancia magnética clínica se clasificaron como: (1) patrón patológico predominante (normal, lesión de la sustancia blanca [WMI]; lesión de la materia gris; lesiones vasculares focales [FVI]; malformaciones; o varios); y (2) lesiones focales (ganglios frontales, basales y / o tálamo). Las evaluaciones incluyeron: (1) desempeño bimanual; (2) destreza unimanual; y (3) tareas de funciones ejecutivas (procesamiento de información, control de atención, flexibilidad cognitiva y fijación de objetivos) y calificaciones de comportamiento (padres). RESULTADOS: De 131 niños reclutados, 60 no fueron elegibles para el análisis, dejando 71 niños (47 varones, 24 mujeres) en la muestra final (edad media 9 años [DE 2 años], 6 años - 12 años 8 meses). Las RMN cerebrales fueron WMI (69%) y FVI (31%); y frontal (59%), talámico (45%), ganglios basales (37%) y ganglios basales más talámico (21%). El rendimiento bimanual fue menor en FVI versus WMI (p0,003), y con lesiones frontales (p = 0,36), ganglios basales (p = 0,032) y talámicas / ganglios basales (p = 0,013). Aparte del procesamiento de la información, las tareas de la función ejecutiva no se asociaron con el patrón predominante. Las lesiones frontales predijeron el control de la atención (p = 0,049) y la flexibilidad cognitiva (p = 0,009) pero no el establecimiento de objetivos, el procesamiento de la información o las clasificaciones de comportamiento. INTERPRETACIÓN: La resonancia magnética cerebral clínica predice los resultados cognitivos y motores cuando se consideran las lesiones focales y los patrones de lesiones predominantes.Imagem por ressonância magnética do cérebro como preditora do desempenho bimanual e função executiva de crianças com paralisia cerebral unilateral OBJETIVO: Examinar a associação entre as características do exame de imagem por ressonância magnética (IRM) e a função executiva e desempenho bimanual em crianças com paralisia cerebral (PC) unilateral. MÉTODO: Escaneamentos clínicos de IRM cerebrais foram classificados como: 1) padrão patológico predominante (normal, lesão da substância branca [LSB]; lesão da substância cinzenta; insultos vasculares focais [IVF]; malformações; ou outro); e (2) lesões focais (frontal, gânglios basais, e/ou tálamo). As avaliações incluíram: (1) desempenho bimanual; (2) destreza unimanual; e (3) tarefas de função executiva (processamento de informações, controle da atenção, flexibilidade cognitiva, e estabelecimento de metas) e pontuações comportamentais (pais). RESULTADOS: De 131 crianças recrutadas, 60 eram inelegíveis para análise, restando 71 crianças (47 do sexo masculino, 24 do sexo feminino) na amostra final (média de idade 9a [DP 2a], 6a-12a 8m). IRMs cerebrais eram do tipo LSB (69%) e IVFs (31%); e frontais (59%), talâmicas (45%), de gânglios da base (37%), e de gânglios da base mais talâmicas (21%). O desempenho bimanual foi menor em IVF versus LSB (p0,003), e com lesões frontais (p=0,36), gânglios da base (p=0,032), e talâmicas/gânglios da base (p=0,013). Com exceção do processamento de informações, as tarefas da função executiva não foram associadas com o padrão predominante. Lesões frontais foram preditivas do controle da atenção (p=0,049) e flexibilidade cognitiva (p=,.009) mas não do estabelecimento de metas, processamento de informações, e pontuações comportamentais. INTERPRETAÇÃO: A IRM cerebral clínica prediz resultados cognitivos e motores quando lesões focais e padrões predominantes de lesão são considerados.

BACKGROUND AND OBJECTIVE Bobath therapy, or neurodevelopmental therapy (NDT) is widely practiced despite evidence other interventions are more effective in cerebral palsy (CP). The objective is to determine the efficacy of NDT in children and infants with CP or high risk of CP. METHODS Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Embase, and Medline were searched through March 2021. Randomized controlled trials comparing NDT with any or no intervention were included. Meta-analysis was conducted with standardized mean differences calculated. Quality was assessed by using Cochrane Risk of Bias tool-2 and certainty by using Grading of Recommendations Assessment, Development, and Evaluation. RESULTS Of 667 records screened, 34 studies (in 35 publications, 1332 participants) met inclusion. Four meta-analyses were conducted assessing motor function. We found no effect between NDT and control (pooled effect size 0.13 [−0.20 to 0.46]), a moderate effect favoring activity-based approaches (0.76 [0.12 to 1.40]) and body function and structures (0.77 [0.19 to 1.35]) over NDT and no effect between higher- and lower-dose NDT (0.32 [−0.11 to 0.75]). A strong recommendation against the use of NDT at any dose was made. Studies were not all Consolidated Standards of Reporting Trials-compliant. NDT versus activity-based comparator had considerable heterogeneity (I2 = 80%) reflecting varied measures. CONCLUSIONS We found that activity-based and body structure and function interventions are more effective than NDT for improving motor function, NDT is no more effective than control, and higher-dose NDT is not more effective than lower-dose. Deimplementation of NDT in CP is required.

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.

To progress stem cell therapies for cerebral palsy, clinicians need to openly engage with patients about emerging evidence and be willing to refer to relevant clinical trials, if and when appropriate. To assess whether education can change clinicians’ confidence in information sharing and willingness to refer to relevant clinical trials, an online questionnaire was distributed at a scientific conference before and after a professional workshop on cell therapies for cerebral palsy. Of the 42 participants who completed the survey, 26 self-identified as clinicians. Of these, 81% had had patients ask about stem cells, yet in the pre-workshop questionnaire indicated they were not confident answering questions about cell therapies. Clinicians were most commonly asked about stem cell treatments provided by private clinics, stem cell research and current evidence. Post-workshop, knowledge and confidence regarding stem cells, as well as likelihood to refer to clinical trials using therapies with a strong evidence base (eg, umbilical cord blood/placental cells), significantly increased (p

BACKGROUND: Perinatal stroke is one of the principal causes of cerebral palsy (CP) in preterm infants. Stroke in preterm infants is different from stroke in term infants, given the differences in brain maturation and the mechanisms of injury exclusive to the immature brain. We conducted a systematic review to explore the epidemiology and pathogenesis of periventricular hemorrhagic infarction (PVHI), perinatal arterial ischemic stroke (PAIS) and cerebral sinovenous thrombosis (CSVT) in preterm infants. METHODS: Studies were identified based on predefined study criteria from MEDLINE, EMBASE, SCOPUS and WEB OF SCIENCE electronic databases from 2000 –2019. Results were combined using descriptive statistics. RESULTS: Fourteen studies encompassed 546 stroke cases in preterm infants between 23 –36 weeks gestational ages and birth weights between 450 –3500 grams. Eighty percent (436/546) of the stroke cases were PVHI, 17%(93/546) were PAIS and 3%(17/546) were CSVT. Parietal PVHI was more common than temporal and frontal lobe PVHI. For PAIS, left middle cerebral artery (MCA) was more common than right MCA or cerebellar stroke. For CSVT partial or complete thrombosis in the transverse sinus was universal. All cases included multiple possible risk factors, but the data were discordant precluding aggregation within a meta-analysis. CONCLUSION: This systematic review confirms paucity of data regarding the etiology and the precise causal pathway of stroke in preterm infants. Moreover, the preterm infants unlike the term infants do not typically present with seizures. Hence high index of clinical suspicion and routine cUS will assist in the timely diagnosis and understanding of stroke in this population.

Introduction Paediatric occupational therapy seeks to improve children's engagement and participation in life roles. A wide variety of intervention approaches exist. Our aim was to summarise the best-available intervention evidence for children with disabilities, to assist families and therapists choose effective care. Methods We conducted a systematic review (SR) using the Cochrane methodology, and reported findings according to PRISMA. CINAHL, Cochrane Library, MEDLINE, OTSeeker, PEDro, PsycINFO were searched. Two independent reviewers: (i) determined whether studies met inclusion: SR or randomised controlled trial (RCT); an occupational therapy intervention for children with a disability; (ii) categorised interventions based on name, core components and diagnostic population; (iii) rated quality of evidence and determined the strength of recommendation using GRADE criteria; and (iv) made recommendations using the Evidence Alert Traffic Light System. Results 129 articles met inclusion (n = 75 (58%) SRs; n = 54 (42%)) RCTs, measuring the effectiveness of 52 interventions, across 22 diagnoses, enabling analysis of 135 intervention indications. Thirty percent of the indications assessed (n = 40/135) were graded 'do it' (Green Go); 56% (75/135) 'probably do it' (Yellow Measure); 10% (n = 14/135) 'probably don't do it' (Yellow Measure); and 4% (n = 6/135) 'don't do it' (Red Stop). Green lights were: Behavioural Interventions; Bimanual; Coaching; Cognitive Cog-Fun & CAPS; CO-OP; CIMT; CIMT plus Bimanual; Context-Focused; Ditto; Early Intervention (ABA, Developmental Care); Family Centred Care; Feeding interventions; Goal Directed Training; Handwriting Task-Specific Practice; Home Programs; Joint Attention; Mental Health Interventions; occupational therapy after toxin; Kinesiotape; Pain Management; Parent Education; PECS; Positioning; Pressure Care; Social Skills Training; Treadmill Training and Weight Loss 'Mighty Moves'. Conclusion Evidence supports 40 intervention indications, with the greatest number at the activities-level of the International Classification of Function. Yellow light interventions should be accompanied by a sensitive outcome measure to monitor progress and red light interventions could be discontinued because effective alternatives existed.

Study Design Two-group randomized controlled trial. Introduction Upper limb orthoses worn during functional tasks are commonly used in pediatric neurologic rehabilitation, despite a paucity of high-level evidence. Purpose of the Study The purpose of this study was to investigate if a customized functional wrist orthosis, when placed on the limb, leads to an immediate improvement in hand function for children with cerebral palsy or brain injury. Methods A 2-group randomized controlled trial involving 30 children was conducted. Participants were randomized to either receive a customized functional wrist orthosis (experimental, n = 15) or not receive an orthosis (control, n = 15). The box and blocks test was administered at baseline and repeated 1 hour after experimental intervention, with the orthosis on if randomized to the orthotic group. Results After intervention, there were no significant differences on the box and blocks test between the orthotic group (mean, 10.13; standard deviation, 11.476) and the no orthotic group (mean, 14.07; standard deviation, 11.106; t[28], −0.954; P = .348; and 95% confidence interval, −12.380 to 4.513). Discussion In contrast to the findings of previous studies, our results suggest that a functional wrist orthosis, when supporting the joint in a ‘typical’ position, may not lead to an immediate improvement in hand function. Conclusions Wearing a functional wrist orthosis did not lead to an immediate improvement in the ability of children with cerebral palsy or brain injury to grasp and release. Further research is needed combining upper limb orthoses with task-specific training and measuring outcomes over the medium to long term.

Background: Stem cells offer great hope and promise as a potential treatment for human diseases. The aim of this study was to gain insight into the public perception of stem cells for neurological conditions. Materials & methods: A paper-based questionnaire was administered to all attendees of a free, public stem cell forum. Results: Of 203 respondents, >95% believe that stem cells have the potential to treat neurological conditions. There was also high support (92%) for the use of embryonic/fetally derived cells, and 67% of respondents indicated a high likelihood to participate in a clinical trial of stem cell treatment(s), indicating overall support for research and translation. Conclusion: Our data demonstrates a positive perception of stem cell treatments for neurological conditions in our cohort.

In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent-offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1A and CTNNB1) met genome-wide significance. We identified two novel monogenic etiologies, FBXO31 and RHOB, and showed that the RHOB mutation enhances active-state Rho effector binding while the FBXO31 mutation diminishes cyclin D levels. Candidate cerebral palsy risk genes overlapped with neurodevelopmental disorder genes. Network analyses identified enrichment of Rho GTPase, extracellular matrix, focal adhesion and cytoskeleton pathways. Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in a Drosophila reverse genetics screen. We estimate that 14% of cases could be attributed to an excess of damaging de novo or recessive variants. These findings provide evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy.

Context: Placental pathology may be an important missing link in the causal pathway of perinatal stroke. The study aim was to systematically review the literature regarding the role of the placenta in perinatal stroke. MEDLINE, Embase, Scopus, and Web of Science electronic databases were searched from 2000 to 2019. Studies were selected based on predefined criteria. To enable comparisons, placental abnormalities were coded using Redline’s classification. Results: Ten studies met the inclusion criteria. Less than a quarter of stroke cases had placental pathology reported. Placental abnormalities were more common among children with perinatal stroke than in the control group. The most frequent placental abnormality was Redline’s category 2 (thrombo-inflammatory process). Conclusions: Placental abnormalities appear to be associated with perinatal stroke, supporting additional indirect evidence and biological plausibility of a causative role. However, the results should be interpreted cautiously considering the low frequency of placental examination and lack of uniformity in placental pathology reporting. Clinical Trial Registration: PROSPERO Registration no: CRD42017081256.

Purpose of ReviewCerebral palsy is the most common physical disability of childhood, but the rate is falling, and severity is lessening. We conducted a systematic overview of best available evidence (2012–2019), appraising evidence using GRADE and the Evidence Alert Traffic Light System and then aggregated the new findings with our previous 2013 findings. This article summarizes the best available evidence interventions for preventing and managing cerebral palsy in 2019.Recent FindingsEffective prevention strategies include antenatal corticosteroids, magnesium sulfate, caffeine, and neonatal hypothermia. Effective allied health interventions include acceptance and commitment therapy, action observations, bimanual training, casting, constraint-induced movement therapy, environmental enrichment, fitness training, goal-directed training, hippotherapy, home programs, literacy interventions, mobility training, oral sensorimotor, oral sensorimotor plus electrical stimulation, pressure care, stepping stones triple P, strength training, task-specific training, treadmill training, partial body weight support treadmill training, and weight-bearing. Effective medical and surgical interventions include anti-convulsants, bisphosphonates, botulinum toxin, botulinum toxin plus occupational therapy, botulinum toxin plus casting, diazepam, dentistry, hip surveillance, intrathecal baclofen, scoliosis correction, selective dorsal rhizotomy, and umbilical cord blood cell therapy.SummaryWe have provided guidance about what works and what does not to inform decision-making, and highlighted areas for more research.

Introduction Neuroplasticity is harnessed through high‐intensity or high‐dose training. Given the costs and time burden for families of children with cerebral palsy (CP), it is important to quantify which rehabilitation training approaches and doses confer the largest clinical gain. The main objective of this systematic review was to determine any threshold dose of upper limb training needed for children with CP to achieve clinically significant functional improvements. Methods This systematic review included studies if they were as follows: randomised controlled trials; participants had a diagnosis of CP or brain injury; mean age of participants was 0–18 years; and intervention was an active upper limb training intervention. Two raters independently extracted data. Data were pooled and analysed using a receiver operator characteristic (ROC) curve and odds ratios to investigate the dose of practice that led to clinically significant gains. Results A total of 74 trials were included in this review. Quantitative analyses included 25 studies (707 participants; age range 18 months to 21 years) for motor function (Assisting Hand Assessment) and 20 studies (491 participants; age range 3 months to 17 years) for individual goal achievement (Canadian Occupational Performance Measure). ROC curve analyses found that approximately 40 hr of practice is needed to improve upper limb motor ability in the unilateral population. For all typographies of CP, individual goals were achieved at a lower dose (14–25 hr) of practice when goal‐directed interventions were provided. Conclusion To improve individual goals, children need to practice goals for more than 14–25 hr, combining face‐to‐face therapy with home practice. To improve general upper limb function (based on evidence in the unilateral population), children need to practice for more than 30–40 hr. Interventions that set functional goals and involve actual practice of those goals lead to goal achievement at a lower dose than general upper limb motor training.

Aim The early diagnosis of cerebral palsy (CP) allows children timely access to early intervention. In 2018, Monash Children's Hospital established an Early Neurodevelopment Clinic based upon evidence-based guidelines for the early diagnosis of CP in high-risk infants. In this study, we aimed to characterise the infants presenting to the clinic and determine the rate of CP diagnosis. Methods This study analysed data from infants attending the Early Neurodevelopment Clinic between May 2019 and April 2020. Infants at high-risk for CP attended the clinic at 3 months corrected age. Neuroimaging reports were reviewed, and a Prechtl's General Movement Assessment and Hammersmith Infant Neurological Examination were performed. Infants were diagnosed as having typical development, delayed development, high-risk of CP or CP at the time of clinic attendance and referred on to the appropriate pathway. Results Ninety-six high-risk infants attended the clinic over the 1 year study period. Sixty-eight (71%) infants were extremely preterm or extremely low birthweight, and 28 (29%) were infants at born at older gestation with evidence of moderate to severe brain injury. Nine (9.6%) infants received a CP diagnosis and 12 (12.5%) were considered high-risk of CP. All infants with CP or high-risk of CP were referred to the Victorian Paediatric Rehabilitation Service. Conclusions It is feasible to implement the early CP diagnosis guidelines into a high-risk infant follow-up clinic. Implementation of the guidelines allows for early diagnosis of CP and appropriate referral of high-risk infants.

Purpose: To assess the nutritional status and underlying risk factors for malnutrition among children with cerebral palsy in rural Bangladesh. Materials and methods: We used data from the Bangladesh Cerebral Palsy Register; a prospective population based surveillance of children with cerebral palsy aged 0-18 years in a rural subdistrict of Bangladesh (i.e., Shahjadpur). Socio-demographic, clinical and anthropometric measurements were collected using Bangladesh Cerebral Palsy Register record form. Z scores were calculated using World Health Organization Anthro and World Health Organization AnthroPlus software. Results: A total of 726 children with cerebral palsy were registered into the Bangladesh Cerebral Palsy Register (mean age 7.6 years, standard deviation 4.5, 38.1% female) between January 2015 and December 2016. More than two-third of children were underweight (70.0%) and stunted (73.1%). Mean z score for weight for age, height for age and weight for height were -2.8 (standard deviation 1.8), -3.1 (standard deviation 2.2) and -1.2 (standard deviation 2.3) respectively. Moderate to severe undernutrition (i.e., both underweight and stunting) were significantly associated with age, monthly family income, gross motor functional classification system and neurological type of cerebral palsy. Conclusions: The burden of undernutrition is high among children with cerebral palsy in rural Bangladesh which is augmented by both poverty and clinical severity. Enhancing clinical nutritional services for children with cerebral palsy should be a public health priority in Bangladesh. Implications for Rehabilitation Population-based surveillance data on nutritional status of children with cerebral palsy in Bangladesh indicates substantially high burden of malnutrition among children with CP in rural Bangladesh. Children with severe form of cerebral palsy, for example, higher Gross Motor Function Classification System (GMFCS) level, tri/quadriplegic cerebral palsy presents the highest proportion of severe malnutrition; hence, these vulnerable groups should be focused in designing nutrition intervention and rehabilitation programs. Disability inclusive and focused nutrition intervention programme need to be kept as priority in national nutrition policies and nutrition action plans specially in low- and middle-income countries. Community-based management of malnutrition has the potential to overcome this poor nutritional scenario of children with disability (i.e., cerebral palsy). The global leaders such as World Health Organization, national and international organizations should take this in account and conduct further research to develop nutritional guidelines for this vulnerable group of population.

Background Recent evidence indicates neonatal surgery is associated with an increased risk of neurodevelopmental disability, including cerebral palsy (CP). Despite evidence for prediction of CP there is limited information on use of the General Movements Assessment (GMA) with this population. Aim To investigate the utility of the GMA for prediction of neurodevelopment in an infant surgical population. Study design Prospective cohort study Subjects: 278 infants following cardiac surgery (n = 149), non-cardiac surgery (n = 123) or both surgeries (n = 6). Outcome measures: GMA at three months of age (mean 12 weeks, SD 1.6) rated by three assessors, two blinded to clinical details. Follow-up at one year of age (mean 372 days, SD 13) using Bayley Scales of Infant and Toddler Development III (BSID-III), clinical and neurological examination. Results: At one year, none of the 248 (89%) infants with normal fidgety movements had a diagnosis of CP, however a large proportion (n = 118, 48%) demonstrated delayed development. Infants who had absent fidgety movements (n = 25, 9%) showed a significant difference on all subtests of the BSID-III (p > 0.05). For prediction of CP there was 100% sensitivity and 96% specificity. Conclusions The GMA is a valid complementary assessment tool to enhance prediction of neurodevelopment, specifically CP, following early neonatal surgery and should be incorporated into routine follow-up for this population.

Background Neonates who undergo major surgery are at risk of neurodevelopmental disability. The General Movements Assessment (GMA) is a valid and reliable method to predict neurodevelopment, however, there are minimal data on the applicability among infants post-surgery. Aim To describe GMs trajectories following neonatal surgery. Study design Prospective cohort study. Subjects 217 infants following major cardiac and non-cardiac neonatal surgery. Outcome measures Infants were assessed following surgery at term age (mean 40 weeks, SD 2.3), and at 3 months of age (mean 12 weeks, SD 1.6) using the GMA and the Bayley Scales of Infant and Toddler Development III. GMA videos were independently scored by three advanced trained assessors, two blinded to infant details. Results The most common result in the writhing period was ‘poor repertoire’ (n = 117, 54%), however, 99 (84%) of these infants had normal fidgety movements. For infants with normal writhing (n = 75, 34%), only four had absent fidgety movements. Cramped synchronised movements were seen in 10 infants, and three of these were rated as absent fidgety. There was no significant difference between the surgical groups. In total, 24 infants (11%) had absent fidgety movements and lower scores on average in all subtests of the BSID-III than those with normal fidgety movements. Conclusions This is the first report describing GMs trajectories in infants who have undergone neonatal surgery. Similar to other high risk infant populations, this group showed a high proportion of poor repertoire writhing movements, however, most infants demonstrated normal fidgety movements and development at 3 months of age.

Background The General Movements Assessment (GMA) is a validated and reliable method of identifying infants at risk of adverse neurodevelopmental outcomes, however there is minimal data available on the use of the GMA with infants following surgery. Aims The aim of this study was to investigate the inter-observer agreement for the GMA with this infant population. Study design Reliability and agreement study. Subjects This was a prospective cohort study of 190 infants (male n=112) born at term (mean 38weeks, SD 2weeks). Outcome measures A GMA was conducted in the Neonatal Intensive Care Unit (NICU) following either cardiac surgery (n=92), non-cardiac surgery (n=93) or both types of surgery (n=5), and then again at three months of age. All videos were independently assessed by three advanced trained clinicians. Agreement and reliability statistics were calculated between each pair. Results We found moderate to substantial levels of agreement in the writhing period (66–77%, AC 1 =0.53–0.69). For fidgety general movements, agreement was classified as almost perfect, ranging from 86 to 89% (AC 1 =0.84–0.88). Conclusions The GMA has high levels of inter-observer agreement when used with infants who have undergone surgery in the neonatal period, making it a valid, complementary assessment tool. Research is now underway to determine the ability of the GMA to predict neurodevelopmental outcomes in this population.

Conveying a diagnosis of a disability to the parents of young children is difficult both for the parent and the clinician, however there is an ethical and medical imperative to do so. However, the process and manner of disclosure needs to be done well. When communication between parent and clinicians fails, parental mental health can be adversely affected. This paper adapts and explains how to use the SPIKES protocol to deliver "bad news" about a developmental disability diagnosis with families of infants

Early detection of childhood disability is possible using clinically available tools and procedures. Early detection of disability enables early intervention that maximizes the child's outcome, prevents the onset of complications, and supports parents. In this chapter, first we summarize the best-available tools for accurately predicting major childhood disabilities early, including autism spectrum disorder, cerebral palsy, developmental coordination disorder, fetal alcohol spectrum disorder, intellectual disability, hearing impairment, and visual impairment. Second, we provide an overview of the preclinical and clinical evidence for inducing neuroplasticity following brain injury. Third, we describe and appraise the evidence base for: (a) training-based interventions that induce neuroplasticity, (b) rehabilitation interventions not focused on inducing neuroplasticity, (c) complementary and alternative interventions, (d) environmental enrichment interventions in the neonatal intensive care and community settings, and (e) parent-child interaction interventions in the neonatal intensive care and community settings. Fourth, we explore emergent treatment options at clinical trial, designed to induce brain repair following injury. In conclusion, early diagnosis enables early intervention, which improves child and parent outcomes. We now know which interventions provide the biggest gains and the information can be used to help inform parental decision making when designing treatment plans for their children.

Cerebral palsy (CP) is a permanent motor disorder that results from brain injury and neuroinflammation during the perinatal period. Mesenchymal stromal cells (MSCs) have been explored as a therapy in multiple adult neuroinflammatory conditions. Our study examined the therapeutic benefits of intranasal delivery of human umbilical cord tissue (UC) derived-MSCs in a rat model of neonatal hypoxic&ndash, ischemic (HI) brain injury. To do this, HI was performed on postnatal day 10 Sprague-Dawley rat pups via permanent ligation of the left carotid artery, followed by a hypoxic challenge of 8% oxygen for 90 min. A total of 200,000 UC-MSCs (10 million/kg) were administered intranasally 24 h post-HI. Motor control was assessed after seven days, followed by post-mortem. Analysis included brain immunohistochemistry, gene analysis and serum cytokine measurement. Neonatal HI resulted in brain injury with significant loss of neurons, particularly in the hippocampus. Intranasal administration of UC-MSCs significantly reduced the loss of brain tissue and increased the number of hippocampal neurons. HI significantly upregulated brain inflammation and expression of pro-inflammatory cytokines, while intranasal UC-MSCs significantly reduced markers of neuroinflammation. This study demonstrated that a clinically relevant dose (10 million/kg) of UC-MSCs was neuroprotective following HI by restoring neuronal cell numbers and reducing brain inflammation. Therefore, intranasal delivery of UC-MSCs may be an effective therapy for neonatal brain injury.

The Insider’s Guide to Protocolized Pediatric Goal-Centered Home Programs following Botulinum Toxin Injections: A commentary on Development of a Pediatric Goal-Centered Upper Limb Spasticity Home E...

Background Cerebral palsy (CP) is caused by a lesion in the developing infant brain. Recent neuroplasticity literature suggests that intensive, task-specific intervention ought to commence early, during the critical period of neural development. Aims To determine whether ⿿GAME⿿ (Goals ⿿ Activity ⿿ Motor Enrichment), a motor learning, environmental enrichment intervention, is effective for improving motor skills in infants at high risk of CP. Methods and procedures Single blind randomised controlled trial of GAME versus standard care. Primary outcome was motor skills on the Peabody Developmental Motor Scales-2 (PDMS-2). Secondary outcomes included Canadian Occupational Performance Measure (COPM), Bayley Scales of Infant and Toddler Development (BSID-III) and Gross Motor Function Measure-66 (GMFM-66). Outcome assessors were masked to group allocation and data analyzed with multiple regression. Outcomes and results All n = 30 infants enrolled received the assigned intervention until 16 weeks post enrolment. At 12 months of age, n = 26 completed assessments. Significant between group differences were found in raw scores on the PDMS-2 in favour of GAME (B = 20.71, 95%CI 1.66⿿39.76, p = 0. 03) and at 12 months on the total motor quotient (B = 8.29, 95%CI 0.13⿿16.45,p = 0.05). Significant between group differences favored GAME participants at 12 months on the cognitive scale of the BSID-III and satisfaction scores on the COPM. Conclusion GAME intervention resulted in advanced motor and cognitive outcomes when compared with standard care.

Evidence for stem cells as a potential intervention for cerebral palsy is emerging. Our objective was to determine the efficacy and safety of stem cells for improving motor and cognitive function of people with cerebral palsy. Searches were conducted in October 2015 in CENTRAL, EMBASE, MEDLINE, and Cochrane Libraries. Randomized controlled trials and controlled clinical trials of stem cells for cerebral palsy were included. Two authors independently decided upon included trials, extracted data, quality, and risk of bias. The primary outcome was gross motor function. Secondary outcomes were cognitive function and adverse events (AEs). Effects were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI), using a random-effects model. Five trials comprising 328 participants met inclusion criteria. Four cell types were studied: olfactory ensheathing, neural, neural progenitors, and allogeneic umbilical cord blood (UCBs). Transplantation procedures differed from central nervous system neurosurgical transplantation to intravenous/arterial infusion. Participants were followed short-term for only 6 months. Evidence of variable quality indicated a small statistically significant intervention effect from stem cells on gross motor skills (SMD 1.27; 95% CI 0.22, 2.33), with UCBs most effective. There were insufficient and heterogeneous data to compare cognitive effects. Serious AEs were rare (n = 4/135 [3%] stem cells; n = 3/139 [2%] controls). Stem cells appeared to induce short-term improvements in motor skills. Different types of stem cell interventions were compared, meaning the data were heterogeneous and are a study limitation. Further randomized controlled trials are warranted, using rigorous methodologies. Significance Stem cells are emerging as a scientifically plausible treatment and possible cure for cerebral palsy, but are not yet proven. The lack of valid animal models has significantly hampered the scope of clinical trials. Despite the state of current treatment evidence, parents remain optimistic about the potential improvements from stem cell intervention and feel compelled to exhaust all therapeutic options, including stem cell tourism. Receiving unproven therapies from unvalidated sources is potentially dangerous. Thus it is essential that researchers and clinicians stay up to date. A systematic review and meta-analysis summarizing and aggregating current research data may provide more conclusive evidence to inform treatment decision making and help direct future research.

IntroductionPreterm brain injury continues to be an important complication of preterm birth, especially in extremely premature infants. Umbilical cord blood-derived cells (UCBCs) are increasingly being evaluated for their neuroprotective and neuroreparative properties in preclinical and clinical studies. There remains a paucity of information on the feasibility and safety of autologous UCBC transplantation in extremely premature infants.Methods and analysisA single centre safety and feasibility study in preterm babies born before 28 weeks gestation. Cord blood will be collected after birth and if sufficient blood is obtained, UCB mononuclear cells will be harvested from the cord blood, characterised and stored. After excluding infants who have already suffered severe preterm brain injury, based on cranial ultrasounds in first week of life, preterm infants will be infused with autologous UCBCs via the intravenous route at a dose of 25–50 million UCBCs/kg body weight of live cells, with the cell number being the maximum available up to 50 million cells/kg. A minimum of 20 infants will be administered autologous UCBCs. Primary outcomes will include feasibility and safety. Feasibility will be determined by access to sufficient cord blood at collection and UCBCs following processing. Safety will be determined by lack of adverse events directly related to autologous UCBC administration in the first few days after cell administration. Secondary outcomes studied will include neonatal and neurodevelopmental morbidities till 2 years of life. Additional outcomes will include cell characteristics of all collected cord blood, and cytokine responses to cell administration in transplanted infants till 36 weeks’ corrected age.Ethics and disseminationMonash Health Human Research Ethics Committee approved this study in December 2019. Recruitment is to commence in July 2020 and is expected to take around 12 months. The findings of this study will be disseminated via peer-reviewed journals and at conferences.Trial registration numberACTRN12619001637134.

IntroductionCerebral palsy (CP) is the most common physical disability of childhood but has no cure. Stem cells have the potential to improve brain injury and are proposed as a therapy for CP. However, many questions remain unanswered about the most appropriate cell type, timing of infusions, dose required and associated risks. Therefore, human safety and efficacy trials are necessary to progress knowledge in the field.Methods and analysisThis is a single group study with sample size n=12 to investigate safety of single-dose intravenous 12/12 human leucocyte antigen-matched sibling cord blood cell infusion to children with CP aged 1–16 years without immune suppression. The study is similar to a 3+3 design, where the first two groups of participants have severe CP, and the final six participants include children with all motor severities. Children will be monitored for adverse events and the duration that donor cells are detected. Assessments at baseline, 3 and 12 months will investigate safety and preliminary evidence of change in gross motor, fine motor, cognitive and quality of life outcomes.Ethics and disseminationFull approval was obtained from The Royal Children’s Hospital Human Research Ethics Committee, and a clinical trial notification was accepted by Australia’s Therapeutic Goods Administration. Participant guardian informed consent will be obtained before any study procedures. The main results of this study will be submitted for publication in a peer-reviewed journal.Trial registration numberACTRN12616000403437,NCT03087110.

Infants born preterm are at increased risk of cerebral palsy (CP), with the risk increasing with decreasing gestational age. Although preterm children are at increased risk of CP compared with their term-born peers, most preterm children do not have CP and thus, it is important to have a standardized process for detecting those children at high risk of CP early. A combination of clinical history, neuroimaging, and physical examination is recommended to ensure early, accurate diagnosis. Early detection of CP is essential for timely early intervention to optimize outcomes for children and their families.

Background Of children with hemiplegic cerebral palsy, 75% have impaired somatosensory function, which contributes to learned non-use of the affected upper limb. Currently, motor learning approaches are used to improve upper-limb motor skills in these children, but few studies have examined the effect of any intervention to ameliorate somatosensory impairments. Recently, Sense© training was piloted with a paediatric sample, seven children with hemiplegic cerebral palsy, demonstrating statistically and clinically significant change in limb position sense, goal performance and bimanual hand-use. This paper describes a protocol for a Randomised Controlled Trial of Sense© for Kids training, hypothesising that its receipt will improve somatosensory discrimination ability more than placebo (dose-matched Goal Directed Therapy via Home Program). Secondary hypotheses include that it will alter brain activation in somatosensory processing regions, white-matter characteristics of the thalamocortical tracts and improve bimanual function, activity and participation more than Goal Directed Training via Home Program. Methods and design This is a single blind, randomised matched-pair, placebo-controlled trial. Participants will be aged 6–15 years with a confirmed description of hemiplegic cerebral palsy and somatosensory discrimination impairment, as measured by the sense©_assess Kids. Participants will be randomly allocated to receive 3h a week for 6 weeks of either Sense© for Kids or Goal Directed Therapy via Home Program. Children will be matched on age and severity of somatosensory discrimination impairment. The primary outcome will be somatosensory discrimination ability, measured by sense©_assess Kids score. Secondary outcomes will include degree of brain activation in response to a somatosensory task measured by functional MRI, changes in the white matter of the thalamocortical tract measured by diffusion MRI, bimanual motor function, activity and participation. Discussion This study will assess the efficacy of an intervention to increase somatosensory discrimination ability in children with cerebral palsy. It will explore clinically important questions about the efficacy of intervening in somatosensation impairment to improve bimanual motor function, compared with focusing on motor impairment directly, and whether focusing on motor impairment alone can affect somatosensory ability. Trial registration This trial is registered with the Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000348257. World Health Organisation universal trial number: U1111–1210-1726. Electronic supplementary material The online version of this article (10.1186/s12887-018-1217-5) contains supplementary material, which is available to authorized users.

More than 50% of infants with cerebral palsy (CP) are born at or near term, with the vast majority having pre- or perinatally acquired CP. While some have a clinical history predictive of CP, such as neonatal encephalopathy or neonatal stroke, others have no readily identifiable risk factors. Paediatricians are often required to discriminate generalised motor delay from a variety of other diagnoses, including CP. This paper outlines known causal pathways to CP in term-born infants with a focus on differential diagnosis. Early and accurate diagnosis is important as it allows prompt access to early intervention during the critical periods of brain development. A combination of clinical history taking, standard clinical examination, neuroimaging and genetic testing should be started at the time of referral. Attention to the investigation of common comorbidities of CP, including feeding and sleep difficulties, and referral to early intervention are recommended.

To examine the prevalence, clinical characteristics, and risk factors of cerebral palsy (CP) in children in Bangladesh.The Bangladesh CP Register is an ongoing population-based surveillance database of children with CP from a geographically defined area in Bangladesh. Cases were defined based on Surveillance of CP in Europe and Australian CP Register criteria after clinical assessments and identification by the key informant's method.In total, 726 children with CP were identified between January 2015 and December 2016. Mean age was 7 years 7 months (standard deviation [SD] 4y 6mo; range: 4.8mo-18y; median 7y 1.2mo; 61.8% male, 38.2% female). Mean age at CP diagnosis was 5 years 2 months (SD 3.8). Observed prevalence was 3.4 per 1000 children (95% confidence interval [CI]: 3.2-3.7), resulting in an estimated 233 514 children (95% CI: 219 778-254 118) with CP in Bangladesh. The majority (79.6%) had spastic CP. Altogether, 79.6% of the children with CP had at least one associated impairment (speech 67.6%, intellectual 39.0%, epilepsy 23.7%, visual 10.2%, and hearing 10.2%). In total, 78.2% never received rehabilitation.In Bangladesh, the burden of CP is high, and diagnosis is substantially delayed, limiting opportunities for early intervention. There is a lack of available services and the majority of the children had preventable risk factors.Prevalence of cerebral palsy (CP) is 3.4 per 1000 children in rural Bangladesh. There are an estimated 233 514 children with CP in Bangladesh. The majority have potentially preventable risk factors. Diagnosis of CP is delayed, limiting opportunities for early intervention. There is a lack of available services for children with CP in rural Bangladesh.EPIDEMIOLOGÍA DE LA PARÁLISIS CEREBRAL EN BANGLADESH: UN ESTUDIO DE VIGILANCIA BASADO EN LA POBLACIÓN: OBJETIVO: Examinar la prevalencia, las características clínicas y los factores de riesgo de la parálisis cerebral (PC) en niños en Bangladesh. MÉTODO: El Registro de PC (BCPR siglas en ingles) de Bangladesh es una base de datos de vigilancia basada en la población de niños con PC, de un área geográficamente definida, en Bangladesh. Los casos se definieron siguiendo los criterios de vigilancia de PC en Europa y los criterios del registro de PC australiano, teniendo en cuenta las evaluaciones clínicas y la identificación por el método del informante clave. RESULTADOS: En total, se identificaron 726 niños con PC entre enero del 2015 y diciembre del 2016. La edad media fue de 7 años y 7 meses (desviación estándar [DE] 4ª 6m; rango: 4,8m-18a; mediana 7a 1,2m; 61,8% masculino, 38,2 % femenino). La edad promedio en el diagnóstico de PC fue de 5 años y 2 meses (DE 3.8). La prevalencia observada fue de 3,4 por cada 1.000 niños (intervalo de confianza [IC] del 95%: 3,2-3,7), resultando en un número estimado de 233.514 niños con PC (IC del 95% 219 778-254 118) en Bangladesh. La mayoría (79.6%) tenía PC espástica. En total, el 79.6% de los niños con PC tenían al menos un impedimento asociado (habla 67.6%, intelectual 39.0%, epilepsia 23.7%, visual 10.2% y audición 10.2%). En total, el 78.2% nunca recibió rehabilitación. INTERPRETACIÓN: En Bangladesh, el impacto de PC es alto y el diagnóstico se retrasa sustancialmente, lo que limita las oportunidades de intervención temprana. Hay una falta de servicios disponibles y la mayoría de los niños tenían factores de riesgo prevenibles.UM ESTUDO DE VIGILÂNCIA COM BASE POPULACIONAL: OBJETIVO: Examinar a prevalência, características clínicas, e fatores de risco para paralisia cerebral (PC) em crianças de Bangladesh. MÉTODO: O Registro de PC de Bangladesh (RPCB) é uma base de dados populacional em andamento para vigilância de crianças com PC de uma área geograficamente definida de Bangladesh. Os casos foram definidos com base nos critérios do Vigilância da PC na Europa e do Registro Australiano de PC após avaliação clínica e identificação pelo método pelo informante principal RESULTADOS: No total, 726 crianças com PC foram identificadas entre Janeiro 2015 e Dezembro 2016. A média de idade foi 7 anos e 7 meses (desvio padrão [DP] 4a 6m; variação: 4,8m-18a; mediana 7a 1,2m; 61,8% do sexo masculino, 38,2% do sexo feminino). A média de idade no momento do diagnóstic de PC foi de 5 anos e 2 meses (DP 3,8). A prevalência observada foi 3,4 a cada 1000 crianças (intervalo de confiança [IC] a 95% 3,2-3,7), resultando em uma estimativa de 233.514 crianças (IC 95% 219.778-254.118) com PC em Bangladesh. A maioria (79,6%) tinha PC espástica. No total, 79,6% das crianças com PC tinha pelo menos uma deficiência associada (linguagem 67,6%, intelectual 39,0%, epilepsia 23,7%, visual 10,2%, e auditiva 10,2%). No total, 78,2% nunca recebeu reabilitação. INTERPRETAÇÃO: Em Bangladesh, o peso da PC é alto, e o diagnóstico é substancialmente tardio, limitando as oportunidades de intervenção precoce. Há carência de serviços disponíveis, e a maioria das crianças apresentou fatores de risco preveníveis.

Introduction Cerebral palsy (CP) is the most common childhood physical disability, with 80% estimated to be in low-middle-income countries. This study aims to (1) determine the accuracy of General Movements (GMs)/Hammersmith Infant Neurological Examination (HINE) for detecting CP at 18 months corrected age (CA); (2) determine the effectiveness of a community-based parent-delivered early intervention for infants at high risk of CP in West Bengal, India (Learning through Everyday Activities with Parents for infants with CP; LEAP-CP). Methods This study comprises two substudies: (1) a study of the predictive validity of the GMs and HINE for detecting CP; (2) randomised, double-blinded controlled trial of a novel intervention delivered through peer trainers (Community Disability Workers, CDW) compared with health advice (15 fortnightly visits). 142 infants at high risk of CP (‘absent fidgety’ GMs; ‘high risk score’ on HINE) aged 12–40 weeks CA will be recruited to the intervention substudy, with infants randomised based on a computer-generated sequence. Researchers will be masked to group allocation, and caregivers and CDWs naive to intervention status. Visits will include therapeutic modules (goal-directed active motor/cognitive strategies and LEAP-CP games) and parent education. Health advice is based on the Integrated Management of Childhood Illness, WHO. Infants will be evaluated at baseline, post intervention and 18 months CA. The primary hypothesis is that infants receiving LEAP-CP will have greater scaled scores on the Pediatric Evaluation of Disability Inventory—Computer Adaptive Test (mobility domain) at 18 months compared with health advice. Secondary outcomes include infant functional motor, cognitive, visual and communication development; infant growth; maternal mental health. Ethics and dissemination This study is approved through appropriate Australian and Indian ethics committees (see in text) with families providing written informed consent. Findings from this trial will be disseminated through peer-reviewed journal publications and conference presentations. Trial registration number 12616000653460p; Pre-results.

The overall objective of this systematic review is to identify, critically appraise and synthesize the literature regarding the feeding experiences of caregivers who care for children with cerebral palsy. The specific review question is: What are the experiences of caregivers feeding children with cerebral palsy?

Background Identifying the characteristics of individuals who are most likely to respond to a certain rehabilitation intervention is advantageous for the child, family, clinicians and the healthcare system. Aim To investigate the individual characteristics of children with cerebral palsy or brain injury who responded best to the Cognitive Orientation to daily Occupational Performance (CO-OP) Approach. Methods Post hoc analyses were conducted on 30 participants who participated in CO-OP within a larger randomized controlled trial. Inclusion: cerebral palsy or brain injury; age 4–15 years; Manual Abilities Classification System (MACS) I-IV; goals related to hand function; sufficient cognitive, language and behavioral ability to undertake CO-OP. Outcome measures were the Canadian Occupational Performance Measure (COPM) and Goal Attainment Scale (GAS) collected immediately following the two week intervention period. Results Following CO-OP, 67% (n = 20) of participants showed a statistically significant response on the COPM, and 73%(n = 22) on the GAS. Nine participants were classified as best responders. When compared to non-responders, best responders were more likely to be female (p = .025) and to have received a higher dose of CO-OP (p = .028). Neither age nor MACS were predictors of response. Conclusion To be successful in CO-OP, children should meet the prerequisites of CO-OP, particularly the language and cognitive ability to set goals and communicate effectively with the therapist. In this small sample, children with comorbidities were less likely to achieve goals, females were more likely to respond and dose of therapy was important to success.