Pathogenetic Insights into Developmental Coordination Disorder Reveal Substantial Overlap with Movement Disorders

Developmental Coordination Disorder (DCD) is a neurodevelopmental condition characterized by non-progressive central motor impairments. Mild movement disorder features have been observed in DCD. Until now, the etiology of DCD has been unclear. Recent studies suggested a genetic substrate in some patients with DCD, but comprehensive knowledge about associated genes and underlying pathogenetic mechanisms is still lacking. In this study, we first identified genes described in the literature in patients with a diagnosis of DCD according to the official diagnostic criteria. Second, we exposed the underlying pathogenetic mechanisms of DCD, by investigating tissue- and temporal gene expression patterns and brain-specific biological mechanisms. Third, we explored putative shared pathogenetic mechanisms between DCD and frequent movement disorders with a known genetic component, including ataxia, chorea, dystonia, and myoclonus. We identified 12 genes associated with DCD in the literature, which are ubiquitously expressed in the central nervous system throughout brain development. These genes are involved in cellular processes, neural signaling, and nervous system development. There was a remarkable overlap (62%) in pathogenetic mechanisms between DCD-associated genes and genes linked with movement disorders. Our findings suggest that some patients might have a genetic etiology of DCD, which could be considered part of a pathogenetic movement disorder spectrum.</p

Applicability of quantitative oculomotor and SARA assessment in children

BACKGROUND: In clinical practice, eye movements can provide an early diagnostic marker for early onset ataxia (EOA). However, quantitative oculomotor assessment is not included in the most frequently used and age-validated ataxia rating scale in children, the Scale for the Assessment and Rating of Ataxia (SARA). We aimed to investigate the applicability of semi-quantitative eye movement assessment by the International Cooperative Ataxia Rating Scale (ICARSOCM) and Ocular Motion Score (OMS7-10) complementary to SARA measurements in children. METHODS: In 52 typically developing children (aged 4-16 years; n = 4 per year of age), three independent assessors scored saccadic eye movements and ocular pursuit according to the ICARSOCM and matching parameters from the OMS7-10. For ICARSOCM, we determined 1) construct validity for coordinated eye movements by correlation with OMS7-10, ICARSEYE-HAND-COORDINATION and SARA subscale scores, 2) agreement percentage and inter-rater agreement (Fleiss Kappa) and 3) age-dependency. RESULTS: Spearman's rank correlations of ICARSOCM with OMS7-10 and ICARS- and SARA subscales were moderate to fair (all p < .001). Inter-rater agreement of ICARS-OCM was 80.8%; (Fleiss Kappa: 0.411). ICARSOCM scores revealed a similar exponentially decreasing association with age as the other SARA (sub)scores, reaching a plateau at 10 years of age. INTERPRETATION: ICARSOCM has a valid construct for the measurement of coordinated eye movement performance and is reliably assessable in children. ICARSOCM reveals a similar age-dependent relationship as the other ataxia subscales, reflecting the physiological maturation of the cerebellum. In children, these data may implicate that ICARSOCM can reliably contribute to coordination assessment, complementary to the SARA subscales

Pathogenetic Insights into Developmental Coordination Disorder Reveal Substantial Overlap with Movement Disorders

Developmental Coordination Disorder (DCD) is a neurodevelopmental condition characterized by non-progressive central motor impairments. Mild movement disorder features have been observed in DCD. Until now, the etiology of DCD has been unclear. Recent studies suggested a genetic substrate in some patients with DCD, but comprehensive knowledge about associated genes and underlying pathogenetic mechanisms is still lacking. In this study, we first identified genes described in the literature in patients with a diagnosis of DCD according to the official diagnostic criteria. Second, we exposed the underlying pathogenetic mechanisms of DCD, by investigating tissue- and temporal gene expression patterns and brain-specific biological mechanisms. Third, we explored putative shared pathogenetic mechanisms between DCD and frequent movement disorders with a known genetic component, including ataxia, chorea, dystonia, and myoclonus. We identified 12 genes associated with DCD in the literature, which are ubiquitously expressed in the central nervous system throughout brain development. These genes are involved in cellular processes, neural signaling, and nervous system development. There was a remarkable overlap (62%) in pathogenetic mechanisms between DCD-associated genes and genes linked with movement disorders. Our findings suggest that some patients might have a genetic etiology of DCD, which could be considered part of a pathogenetic movement disorder spectrum.</p

2D Gait Skeleton Data Normalization for Quantitative Assessment of Movement Disorders from Freehand Single Camera Video Recordings

Overlapping phenotypic features between Early Onset Ataxia (EOA) and Developmental Coordination Disorder (DCD) can complicate the clinical distinction of these disorders. Clinical rating scales are a common way to quantify movement disorders but in children these scales also rely on the observer's assessment and interpretation. Despite the introduction of inertial measurement units for objective and more precise evaluation, special hardware is still required, restricting their widespread application. Gait video recordings of movement disorder patients are frequently captured in routine clinical settings, but there is presently no suitable quantitative analysis method for these recordings. Owing to advancements in computer vision technology, deep learning pose estimation techniques may soon be ready for convenient and low-cost clinical usage. This study presents a framework based on 2D video recording in the coronal plane and pose estimation for the quantitative assessment of gait in movement disorders. To allow the calculation of distance-based features, seven different methods to normalize 2D skeleton keypoint data derived from pose estimation using deep neural networks applied to freehand video recording of gait were evaluated. In our experiments, 15 children (five EOA, five DCD and five healthy controls) were asked to walk naturally while being videotaped by a single camera in 1280 × 720 resolution at 25 frames per second. The high likelihood of the prediction of keypoint locations (mean = 0.889, standard deviation = 0.02) demonstrates the potential for distance-based features derived from routine video recordings to assist in the clinical evaluation of movement in EOA and DCD. By comparison of mean absolute angle error and mean variance of distance, the normalization methods using the Euclidean (2D) distance of left shoulder and right hip, or the average distance from left shoulder to right hip and from right shoulder to left hip were found to better perform for deriving distance-based features and further quantitative assessment of movement disorders

Neurologic Outcome Comparison between Fetal Open-, Endoscopic- and Neonatal-Intervention Techniques in Spina Bifida Aperta

Introduction: In spina bifida aperta (SBA), fetal closure of the myelomeningocele (MMC) can have a neuroprotective effect and improve outcomes. In Europe, surgical MMC closure is offered by fetal-open (OSBAR), fetal-endoscopic (FSBAR), and neonatal (NSBAR) surgical techniques. Pediatric neurologists facing the challenging task of counseling the parents may therefore seek objective outcome comparisons. Until now, such data are hardly available. In SBA, we aimed to compare neurologic outcomes between OSBAR, FSBAR, and NSBAR intervention techniques. Methods: We determined intervention-related complications, neuromuscular integrity, and neurologic outcome parameters after OSBAR (n = 17) and FSBAR (n = 13) interventions by age- and lesion-matched comparisons with NSBAR-controls. Neurological outcome parameters concerned: shunt dependency, segmental alterations in muscle ultrasound density (reflecting neuromuscular integrity), segmental motor-, sensory- and reflex conditions, and the likelihood of intervention-related gain in ambulation. Results: Compared with NSBAR-controls, fetal intervention is associated with improved neuromuscular tissue integrity, segmental neurological outcomes, reduced shunt dependency, and a higher chance of acquiring ambulation in ≈20% of the operated children. Children with MMC-lesions with a cranial border at L3 revealed the most likely intervention-related motor function gain. The outcome comparison between OSBAR versus FSBAR interventions revealed no significant differences. Conclusion: In SBA, OSBAR- and FSBAR-techniques achieved similar neuroprotective results. A randomized controlled trial is helpful in revealing and compare ongoing effects by surgical learning curves.</p

Neurologic Outcome Comparison between Fetal Open-, Endoscopic- and Neonatal-Intervention Techniques in Spina Bifida Aperta

Introduction: In spina bifida aperta (SBA), fetal closure of the myelomeningocele (MMC) can have a neuroprotective effect and improve outcomes. In Europe, surgical MMC closure is offered by fetal-open (OSBAR), fetal-endoscopic (FSBAR), and neonatal (NSBAR) surgical techniques. Pediatric neurologists facing the challenging task of counseling the parents may therefore seek objective outcome comparisons. Until now, such data are hardly available. In SBA, we aimed to compare neurologic outcomes between OSBAR, FSBAR, and NSBAR intervention techniques. Methods: We determined intervention-related complications, neuromuscular integrity, and neurologic outcome parameters after OSBAR (n = 17) and FSBAR (n = 13) interventions by age- and lesion-matched comparisons with NSBAR-controls. Neurological outcome parameters concerned: shunt dependency, segmental alterations in muscle ultrasound density (reflecting neuromuscular integrity), segmental motor-, sensory- and reflex conditions, and the likelihood of intervention-related gain in ambulation. Results: Compared with NSBAR-controls, fetal intervention is associated with improved neuromuscular tissue integrity, segmental neurological outcomes, reduced shunt dependency, and a higher chance of acquiring ambulation in ≈20% of the operated children. Children with MMC-lesions with a cranial border at L3 revealed the most likely intervention-related motor function gain. The outcome comparison between OSBAR versus FSBAR interventions revealed no significant differences. Conclusion: In SBA, OSBAR- and FSBAR-techniques achieved similar neuroprotective results. A randomized controlled trial is helpful in revealing and compare ongoing effects by surgical learning curves.</p