Evaluation of Experienced Clinical Events in Pompe Disease Based on Real-life Data.

ObjectiveTo evaluate whether prenatal exposure to specific antiseizure drugs increases the risk of neurodevelopmental disorders in children.DesignPopulation based cohort study.SettingHealthcare use data from publicly and commercially insured beneficiaries in the United States, 2000-21.ParticipantsPregnant patients with epilepsy linked to offspring.InterventionsDispensing of the antiseizure drug of interest during the second half of pregnancy (synaptogenesis period): carbamazepine, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, valproate, and zonisamide. The reference group consisted of pregnant patients with diagnosed epilepsy, but no antiseizure drug dispensation from three months before pregnancy until delivery.Main outcomes measuresAny neurodevelopmental disorder, attention deficit hyperactivity disorder, autism spectrum disorder, behavioral disorder, developmental coordination disorder, intellectual disability, learning difficulty, and speech or language disorder identified using validated algorithms. Hazard ratios were estimated using Cox proportional hazard models with propensity score overlap weighting to adjust for potential confounders.ResultsThe cohort included 8887 children who were prenatally unexposed. Exposed pregnancies ranged from 219 for lacosamide to 5261 for levetiracetam. Valproate and zonisamide showed associations with several outcomes (adjusted hazard ratio range 1.26-4.50), whereas levetiracetam and phenytoin were not associated with an increased risk of any outcome. Several drugs were associated with a two to fourfold risk increase for intellectual disability, but estimates were imprecise because of the small number of children with this disorder. Although no meaningful associations were found for topiramate and lamotrigine across most outcomes, there was a potential signal for intellectual disability (both drugs) and learning difficulty (topiramate only; hazard ratio 1.23 based on small numbers). Carbamazepine and oxcarbazepine showed a modest risk increase for attention deficit hyperactivity disorder and behavioral disorders (hazard ratio range 1.23-1.40). Results were robust across several sensitivity analyses, including using lamotrigine as an active comparator.ConclusionsThe findings strengthen the evidence for increased neurodevelopmental risks among children with prenatal valproate exposure and suggest the need for further evaluation of zonisamide. Signals for other antiseizure drugs, observed in the context of several comparisons and rare outcomes, require confirmation as data accumulate.

Approximately 5% of children are affected by a neurodevelopmental disorder of their sensorimotor skills. DSM-V and ICD-10, the two most widely used diagnostic systems, define this diagnostically as 'Developmental Coordination Disorder' (DCD) or 'Specific Developmental Disorder of Motor Function' (SDDMF), respectively. A diagnosis of DCD has been found to have a detrimental impact on a range of outcomes (e.g., health and education). It is therefore crucial that these children receive timely intervention. This is reliant, however, on effective assessment and support pathways. Research has shown there is great parental dissatisfaction, but there has been limited research exploring a clinical and education perspective. This study therefore aimed to understand barriers and facilitators for clinical and education practitioners in the pathway in a diverse district in the UK (Bradford). Semi-structured interviews were completed with stakeholders across the pathway to identify barriers and facilitators to assessing, diagnosing, and supporting children with sensorimotor skill difficulties. Theoretical thematic analysis aligned to the Capability, Opportunity, Motivation model of Behaviour change (COM-B) was used to analyse the qualitative data. Interviews revealed many barriers in the DCD pathway related to capability (confusing terminology, inconsistent knowledge, inappropriate referrals), opportunity (resource constraints, DCD being considered low priority, and disconnected services), and motivation (overlapping job roles, a desire to consider those with difficulties not eligible for a diagnosis). No facilitators were consistently identified across interviews. Families face multiple barriers to obtaining a diagnosis for their child through existing clinical pathways for assessment and support. These findings are unlikely to be unique to Bradford, due to international research highlighting these issues via parental interviews. These findings therefore may reflect challenges both nationally and internationally within DCD pathways. There is an urgent need for: (i) clear communication across different services (with consistency in terminology), and (ii) a more collaborative and integrated approach to assessment, diagnosis, and support in order to help these children thrive.

Developmental Coordination Disorder (DCD) often persists into adulthood. However standardized diagnostic tools for adults remain rare. This study aimed to validate the Czech version of the Adult Developmental Coordination Disorder/Dyspraxia Checklist (ADC) and to standardize a novel battery of tests for assessing practical and gnostic cortical functions. The sample consists of 99 adults (18–40 years; mean age 26.3). Participants underwent a newly designed battery of 11 motor and sensory tests and completed the ADC questionnaire. Reliability was assessed using Cohen’s kappa and Cronbach’s alpha (ɑ). The Czech ADC questionnaire demonstrated excellent internal consistency with the value of Cronbach’s alpha (ɑ=0.93). The test battery showed high inter-rater reliability by Cohen’s kappa (κ=0.89). Deficits were identified in 8–12% of the sample. No significant Cohen’s kappa gender differences were found in objective performance (p > 0.05). The Petrie´’s Test exhibited the highest correlation with subjective self-assessment. The study presents a valid and reliable protocol for screening cortical deficits. The normative data allow the identification of subtle neurodevelopmental impairments in clinical and sports practice in the screening of adult population.

Emotional outcomes are poorer in adults with developmental coordination disorder: A systematic review and meta-analyses.

Distal arthrogryposis with impaired proprioception and touch: description of 9 additional cases harbouring novel PIEZO2 variants and literature review.

Predicting fine motor deficit in autism by measuring brain activities and characterizing motor impairments.

Clinical Manifestations and Genetic Insights Into Congenital Myasthenic Syndrome-22 in Pediatric Patients.

Abstract Objectives Children with neurodevelopmental disorders make up a significant proportion of the Child and Adolescent Mental Health Services (CAMHS) population. Early identification of children at risk for developing mental and physical co-morbidities and appropriate multidisciplinary management, including physiotherapy, is vital to improve health outcomes. The primary aim of this systematic review was to clarify the evidence available around the application of physiotherapeutic interventions within CAMHS populations presenting with neurodevelopmental disorders. Methods A systematic review of randomised controlled trials exploring physiotherapeutic interventions for children and young people (aged 5–18 years) with neurodevelopmental disorders was conducted. Results Meta-analysis demonstrated a significant total effect favouring physiotherapeutic intervention for improving postural stability in children and young people with Developmental Coordination Disorder(DCD) (WMD 4.27 [95% CI 1.87, 6.68]; p = 0.0005). Additionally, children with DCD, Autism, Attention Deficit Hyperactivity Disorder, Dyslexia, and Intellectual Disabilities were found to see improvements in motor proficiency; muscle strength; self-concept, participation, and function; behaviour; respiratory function; and gait from primarily exercise as well as other physiotherapeutic interventions. Conclusions For children and young people presenting to CAMHS with neurodevelopmental disorders, physiotherapeutic interventions can be applied to improve a variety of health outcomes, however, the evidence to support this is of low quality.

To identify, qualify, and synthesize the characteristics of interventions for children with diagnosed and suspected developmental coordination disorder (DCD) worldwide. This was a scoping review, with searches in eight bibliographical databases without language restrictions. All interventions involving children and adolescents with motor coordination disorders were included, with content analyses involving the type and context of the intervention and interventionists, the outcomes addressed, and the findings reported and considered regarding the International Classification of Functioning, Disability and Health framework. From 30 637 hits, 202 distinct studies were identified, including 206 interventions with a total of 4593 children or adolescents. The children included were often poorly defined. Movement activities were offered through task-oriented, motor skill, and sports training approaches with active video games and sensory-perceptual motor skills training reported the most frequently. Long-term psychosocial and participation outcomes were less explored. Future intervention studies need to be clearer on the diagnostic criteria and details of DCD, including individual(s) who delivered the training, the type of training, session intensity, and the delivery mode. Outcome measures should consider three critical domains: (1) practical application of learned motor skills in daily life; (2) environmental and psychosocial impacts; and (3) parental awareness and support.

Toward preventive interventions in developmental coordination disorder: in need of early behavioral markers?

One of the essential motor skills in children’s lives is obstacle crossing. This ability is frequently employed in everyday scenarios, such as stepping over toys or miscellaneous objects on the floor. In a real-life context, the execution of this task is often influenced by concurrent cognitive demands, leading to potential cognitive-motor interference. Its effect could be more apparent in younger children or children with some motor difficulties. Thus, the aim of this study is to assess the obstacle crossing performance and post-obstacle movement under single and dual-task conditions (motor and visual discrimination task) in children with developmental coordination disorder (DCD) and typically developing (TD) children of various ages. A total of 110 children aged from 7 to 12 years (35 DCD, 75 TD) participated in the study. They performed obstacle crossing task under single and two dual-task conditions (simple, complex-inhibit). The results showed significant effect of group only for centre of pressure velocity in medial-lateral direction during post-obstacle stance phase with higher values (worse balance) in DCD children. In addition, children with DCD also showed later propulsion during dual-tasking compared with single locomotor task, while TD children had comparable values for both conditions. The effect of age was significant in all aspects of the task including obstacle crossing performance, landing, dynamic balance and propulsion. Older children compared to younger can be characterized by a more effective strategy for obstacle crossing with smaller braking and faster gait initiation after obstacle crossing.

Aromatic ʟ-amino acid decarboxylase (AADC) deficiency is a rare pediatric neurotransmitter disorder that typically necessitates lifelong care, and that carries a risk of childhood mortality. Eladocagene exuparvovec gene therapy is designed to restore AADC production. Study GT-002 (NCT04903288) is a phase 2, multicenter, open-label trial assessing the pharmacodynamics, safety, and efficacy of eladocagene exuparvovec administered to the putamen bilaterally in pediatric patients with AADC deficiency using a magnetic resonance (MR)-compatible cannula. Patients received eladocagene exuparvovec at 1.8 × 1011 vector genomes via the SmartFlow MR-compatible cannula in a single operative session. Endpoints include the change from baseline in cerebrospinal fluid homovanillic acid levels, motor milestone achievement, and safety. Here we report results from 48 weeks of follow-up. Mean (SD) cerebrospinal fluid homovanillic acid levels increased from baseline (22.5 [32.3] nmol/L; n = 13) to week 48 (55.3 [45.6] nmol/L; change from baseline: 28.3 [13.7] nmol/L; p = 0.0003; n = 9), indicating de novo dopamine production. At baseline (n = 13), all patients showed severe motor developmental delay; at week 48 (n = 12), nine achieved full head control, four could sit unassisted, two could stand with support, and two could walk independently to a toy. Overall, 260 treatment-emergent adverse events were reported in 13 patients; 259 were deemed unrelated and one likely unrelated to the MR-compatible cannula. No treatment-emergent adverse events led to study withdrawal and no deaths occurred. This study provides further evidence of the favorable pharmacodynamic, efficacy, and safety profile of eladocagene exuparvovec in children with AADC deficiency; intraputaminal administration using an MR-compatible cannula was well tolerated. Study GT-002 (NCT04903288) provides further evidence of the favourable pharmacodynamic, efficacy and safety profile of eladocagene exuparvovec gene therapy in children with AADC deficiency over 48 weeks and demonstrates that intraputaminal administration using an MR-compatible cannula was well tolerated, allowing for real-time MRI confirmation of cannula placement and infusate coverage, and for accurate dosing to the putamen.

Developmental Coordination Disorder (DCD) is a neurodevelopmental motor disorder characterised by marked difficulties in the acquisition and execution of motor skills, substantially affecting daily activities and quality of life. Martial arts (MAs), due to their multi-skilled nature, have been studied as possible intervention strategies to improve motor competence and functionality in children with DCD. The present systematic review aimed to explore the effects of MA practice in children and adolescents with DCD, identifying the benefits, methodological characteristics and practical implications of existing interventions. The search was conducted in the PubMed, Web of Science, and EBSCO databases, following the PRISMA 2021 guidelines, using the keywords (developmental coordination disorder OR DCD OR dyspraxia) AND (karate OR judo OR taekwondo OR aikido OR martial art) AND (child OR preschool). Experimental and quasi-experimental studies that applied MA programmes to children and adolescents (≤18 years) with a confirmed diagnosis of DCD were included. Of the 1834 identified records, five studies met the inclusion criteria. The MA modalities examined were karate, tai chi, and taekwondo. Across studies (n per study = 16-145), MA-based programmes consistently yielded significant pre- to post-intervention improvements in overall motor competence (MC), balance, muscle strength, and coordination; one study reported maintenance of coordination gains at 3-month follow-up. Methodological quality assessed with the Downs and Black checklist ranged from fair to good (scores = 18-22). No adverse events were reported. Based on the included studies, MA interventions demonstrate potential as an effective motor intervention approach for children and adolescents with DCD. Findings consistently indicated significant improvements in motor competence, balance, muscle strength, and coordination, with additional benefits observed in cognitive and psychosocial domains and no reported adverse effects.

To assess the association between histological chorioamnionitis without maternal clinical symptoms and neurodevelopmental disabilities at age 5 years in children born very preterm. French national prospective population-based cohort study, EPIPAGE-2 (Etude épidémiologique sur les petits âges gestationnels). All births from 22 to 34 weeks of gestational age in France in 2011 were eligible. Infants born alive between 24+0 and 31+6 weeks following preterm labour (PTL) or preterm premature rupture of membranes (PPROMs). Histological chorioamnionitis without maternal clinical symptoms, also called isolated histological chorioamnionitis, was defined as the presence of neutrophils in the chorionic plate, excluding clinical chorioamnionitis. Neurodevelopmental disabilities, a composite outcome including cerebral palsy, developmental coordination disorders, sensory impairment, developmental cognitive deficiencies or behavioural difficulties. These assessments were comprehensive, standardised and conducted by trained neuropsychologists and paediatricians at age 5 years. Among 1296 children alive at 5 years of age, 486 (36.3%) were born in a context of isolated histological chorioamnionitis. Overall, 47% vs 33.6% of children exposed and not exposed to isolated histological chorioamnionitis had mild neurodevelopmental disabilities, and 13.8% vs 13.3% had moderate-to-severe neurodevelopmental disabilities. After multiple imputation and multivariable analysis, isolated histological chorioamnionitis was found not to be associated with the occurrence of mild or moderate-to-severe neurodevelopmental disabilities (adjusted OR: 1.0, 95% CI: 0.7 to 1.4 and 0.9, 0.6 to 1.2). We did not find any association between isolated histological chorioamnionitis and neurodevelopmental disabilities at age 5 years in children born very preterm after PTL or PPROM.

Early developmental intervention seeks to enhance functional outcomes in preterm infants by leveraging neuroplasticity. We investigated the relationship between early intervention and neurodevelopmental outcomes in early childhood among preterm infants without severe brain injury. This prospective cohort study enrolled very-low-birth-weight infants (23+0-32+6 weeks' gestation) registered in the Korean Neonatal Network. Neurodevelopment was evaluated at corrected ages 18-24 months and chronological ages 33-45 months using the Bayley Scales of Infant and Toddler Development (Second or Third Edition), the Korean Developmental Screening Test, or both. Infants who began motor-based or language therapy prior to 18-24 months of corrected age were defined as the early intervention group. Of the 1797 infants who completed follow-up, 518 (28.8%) received early intervention. Compared to infants without early intervention, those with early intervention had lower gestational age and higher rates of prematurity-related complications and post-discharge rehospitalizations. The interaction between the intervention group and assessment time was statistically significant, indicating that early intervention was associated with a reduced risk of motor developmental delays over time (adjusted odds ratio 0.669, 95% confidence interval 0.472-0.949). Early intervention was associated with more favorable motor outcomes, highlighting the importance of timely support for high-risk preterm infants. Preterm infants with greater medical complexity more commonly received early intervention. Early intervention mitigated the progression of motor developmental delays over time. An enriched early environment may help offset the negative developmental impact of preterm complications.

This study is a scoping review that comprehensively organizes martial arts intervention studies targeting Attention-Deficit/Hyperactivity Disorder (ADHD) and Developmental Coordination Disorder (DCD). Analysis of 17 papers revealed that multiple studies reported improvements in cognitive and socioemotional functioning for ADHD, and in physical fitness components centered on balance for DCD. However, results were inconsistent, and challenges remain regarding the number and quality of studies. Martial arts show potential benefits for physical and psychosocial development, but large-scale, high-quality follow-up studies are still needed.

Children with Developmental Coordination Disorder (DCD) show substantial motor and balance difficulties that affect daily activities. Although action observation (AO) and motor imagery (MI) are effective in other neurological conditions, their impact in DCD remains underinvestigated. This review explores the preliminary evidence of AO- and MI-based interventions for improving motor and functional outcomes in children with DCD. A systematic search of PubMed, Scopus, and Web of Science identified randomized controlled trials and controlled trials published in the last 15 years evaluating AO and MI interventions in children with DCD. Two independent reviewers conducted the screening of the studies, data extraction, and the risk-of-bias assessment using RoB2 and ROBINS-I. The review followed PRISMA reporting guidelines and was pre-registered on the PROSPERO database (CRD420251084196). Of 320 records initially identified, seven studies, involving 199 children with DCD (aged 5-12 years), were included. Interventions varied from single-session to multi-session protocols (1-16 sessions) and included AO, MI, or a combination of both (AO + MI), with heterogeneous control conditions. Within these studies, the outcomes were primarily assessed using standardized motor coordination measures (MABC/MABC-2, DCDQ), planning tasks, and performance-based activities of daily living (ADLs) measures. Improvements were reported in motor imagery tasks, planning, and functional task performance. However, RCTs and CTs were identified to have a moderate and high risk of bias, respectively. The present review suggests that AO and MI, either alone or in combination, may enhance motor planning, coordination, and daily functional skills in children with DCD, supporting internal motor representations and predictive motor control, reflecting functional gain in motor skills and ADL performance. Interestingly, these mental training approaches can be applied in clinical and everyday settings and are suitable for supporting these processes, with VR-based combinations representing a promising, but exploratory, approach. Although critical heterogeneity and a moderate risk of bias remain, the findings need to be interpreted with caution and require further investigation.

Cerebral palsy (CP) is one of the most common causes of physical disability in childhood. While the Gross Motor Function Classification System (GMFCS) describes motor abilities, aunified classification for musculoskeletal pathologies was lacking. The newly proposed four-stage system-based on the Mercer Rang model-describes the progression of lower limb pathology and supports diagnosis, treatment planning, and research. STAGE1: Hypertonia: From birth to about 6 years, spasticity and delayed motor development predominate; contractures are rare. Early intervention and spasticity management (e.g., botulinum toxin) are the focus. STAGE2: Contractures: Between the ages of 4 and 12 years, discrepancies between muscle-tendon length and bone growth cause a reduced range of motion. Surgical muscle or tendon lengthening may be indicated. STAGE3: Bony deformities: Bony deformities such as increased femoral anteversion or pes valgus occur simultaneously with soft tissue contractures; rotational osteotomies and combined multilevel surgeries (SEMLS) are often required. STAGE4: Decompensated pathology: After puberty, irreversible deformities and joint degeneration develop. Surgery usually aims at pain reduction or stabilization (e.g., arthrodesis). This classification raises awareness of disease progression, helps select stage-appropriate treatments, and may prevent over- or undertreatment. Early recognition and intervention are crucial to avoid decompensation and improve long-term musculoskeletal and functional outcomes.

Developmental Coordination Disorder (DCD) is a prevalent neurodevelopmental condition in children which manifests as a marked impairment in the acquisition and execution of coordinated motor abilities. In recent years, Motor Imagery (MI), as a cognitive rehabilitation training method, has garnered considerable attention due to its ability to activate brain region networks similar to those involved in actual movement. It is considered to hold great potential for improving motor skills in children with DCD. This study aims to systematically review the literature to evaluate the effects of motor imagery training on motor abilities (specifically gross motor, fine motor, and balance skills) in children with DCD, and to explore the relative effectiveness of different intervention models (such as MI alone, action observation combined with MI [AOMI], and MI combined with physical practice [MI+PP]).