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Pre- and perinatal complications have been implicated in the onset and clinical expression of Tourette syndrome albeit with considerable inconsistencies across studies. Also, little is known about their role in co-occurring obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in individuals with a tic disorder. Therefore, we aimed to investigate the role of pre- and perinatal complications in relation to the presence and symptom severity of chronic tic disorder and co-occurring OCD and ADHD using data of 1113 participants from the Tourette International Collaborative Genetics study. This study included 586 participants with a chronic tic disorder and 527 unaffected family controls. We controlled for age and sex differences by creating propensity score matched subsamples for both case-control and within-case analyses. We found that premature birth (OR = 1.72) and morning sickness requiring medical attention (OR = 2.57) were associated with the presence of a chronic tic disorder. Also, the total number of pre- and perinatal complications was higher in those with a tic disorder (OR = 1.07). Furthermore, neonatal complications were related to the presence (OR = 1.46) and severity (b = 2.27) of co-occurring OCD and also to ADHD severity (b = 1.09). Delivery complications were only related to co-occurring OCD (OR = 1.49). We conclude that early exposure to adverse situations during pregnancy is related to the presence of chronic tic disorders. Exposure at a later stage, at birth or during the first weeks of life, appears to be associated with co-occurring OCD and ADHD.

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. [ABSTRACT FROM AUTHOR]

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 (ICARS OCM) and Ocular Motion Score (OMS 7-10) complementary to SARA measurements in children. 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 ICARS OCM and matching parameters from the OMS 7-10. For ICARS OCM , we determined 1) construct validity for coordinated eye movements by correlation with OMS 7-10 , ICARS EYE-HAND-COORDINATION and SARA subscale scores, 2) agreement percentage and inter-rater agreement (Fleiss Kappa) and 3) age-dependency. Spearman's rank correlations of ICARS OCM with OMS 7-10 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). ICARS OCM scores revealed a similar exponentially decreasing association with age as the other SARA (sub)scores, reaching a plateau at 10 years of age. ICARS OCM has a valid construct for the measurement of coordinated eye movement performance and is reliably assessable in children. ICARS OCM 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 ICARS OCM can reliably contribute to coordination assessment, complementary to the SARA subscales. Paediatric, semi-quantitative oculomotor parameters (ICARS OCM): • Reveal construct validity with coordinated eye movements as assessed by OMS. • Reveal construct validity with coordinated limb movements, as assessed by ICARS EYE-HAND-COORDINATION and SARA. • Are reliably assessable by paediatric neurologists and researchers. • Are age-dependent until ≈10 years of age, analogous with other SARA-subscale scores. [ABSTRACT FROM AUTHOR]

Background The Burke-Fahn-Marsden Dystonia Rating Scale is a universally applied instrument for the quantitative assessment of dystonia in both children and adults. However, immature movements by healthy young children may also show 'dystonic characteristics' as a consequence of physiologically incomplete brain maturation. This could implicate that Burke-Fahn-Marsden scale scores are confounded by pediatric age. Objective In healthy young children, we aimed to determine whether physiologically immature movements and postures can induce an age-related effect on Burke-Fahn-Marsden movement and disability scale scores. Methods Nine assessors specializied in movement disorders (3 adult neurologists, 3 pediatric neurologists, and 3 MD/PhD students) independently scored the Burke-Fahn-Marsden movement scale in 52 healthy children (4-16 years of age; 2 boys and 2 girls per year of age). Independent of that, parents scored their children's functional motor development according to the Burke-Fahn-Marsden disability scale in another 52 healthy children (4-16 years of age; 2 boys and 2 girls per year of age). By regression analysis, we determined the association between Burke-Fahn-Marsden movement and disability scales outcomes and pediatric age. Results In healthy children, assessment of physiologically immature motor performances by the Burke-Fahn-Marsden movement and disability scales showed an association between the outcomes of both scales and age (until 16 years and 12 years of age, β = −0.72 and β = −0.60, for Burke-Fahn-Marsden movement and disability scale, respectively [both P < 0.001]). Conclusions The Burke-Fahn-Marsden movement and disability scales are influenced by the age of the child. For accurate interpretation of longitudinal Burke-Fahn-Marsden Dystonia Rating Scale scores in young dystonic children, consideration of pediatric age-relatedness appears advisory. [ABSTRACT FROM AUTHOR]

In degenerative adult onset ataxia (AOA), dystonic comorbidity is attributed to one disease continuum. However, in early adult onset ataxia (EOA), the prevalence and pathogenesis of dystonic comorbidity (EOAD+), are still unclear. In 80 EOA-patients, we determined the EOAD+-prevalence in association with MRI-abnormalities. Subsequently, we explored underlying biological pathways by genetic network and functional enrichment analysis. We checked pathway-outcomes in specific EOAD+-genotypes by comparing results with non-specifically (in-silico-determined) shared genes in up-to-date EOA, AOA and dystonia gene panels (that could concurrently cause ataxia and dystonia). In the majority (65%) of EOA-patients, mild EOAD+-features concurred with extra-cerebellar MRI abnormalities (at pons and/or basal-ganglia and/or thalamus (p = 0.001)). Genetic network and functional enrichment analysis in EOAD+-genotypes indicated an association with organelle- and cellular-component organization (important for energy production and signal transduction). In non-specifically, in-silico-determined shared EOA, AOA and dystonia genes, pathways were enriched for Krebs-cycle and fatty acid/lipid-metabolic processes. In frequently occurring EOAD+-phenotypes, clinical, anatomical and biological pathway analyses reveal shared pathophysiology between ataxia and dystonia, associated with cellular energy metabolism and network signal transduction. Insight in the underlying pathophysiology of heterogeneous EOAD+-phenotype-genotype relationships supports the rationale for testing with complete, up-to-date movement disorder gene lists, instead of single EOA gene-panels. [ABSTRACT FROM AUTHOR]

In glycogen storage diseases (GSDs), improved longevity has resulted in the need for neuromuscular surveillance. In 12 children and 14 adults with the "hepatic" (GSD-I) and "myopathic" (GSD-III) phenotypes, we cross-sectionally assessed muscle ultrasound density (MUD) and muscle force. Children with both "hepatic" and "myopathic" GSD phenotypes had elevated MUD values (MUD Z-scores: GSD-I > 2.5 SD vs. GSD-III > 1 SD, p < 0.05) and muscle weakness (GSD-I muscle force; p < 0.05) of myopathic distribution. In "hepatic" GSD-I adults, MUD stabilized (GSD-I adults vs. GSD-I children, not significant), concurring with moderate muscle weakness (GSD-I adults vs. healthy matched pairs, p < 0.05). In "myopathic" GSD-III adults, MUD increased with age (MUD-GSD III vs. age: r = 0.71-0.83, GSD-III adults > GSD-III children, p < 0.05), concurring with pronounced muscle weakness (GSD-III adults vs. GSD-I adults, p < 0.05) of myopathic distribution. Children with "hepatic" and "myopathic" GSD phenotypes were both found to have myopathy. Myopathy stabilizes in "hepatic" GSD-I adults, whereas it progresses in "myopathic" GSD-III adults. Muscle ultrasonography provides an excellent, non-invasive tool for neuromuscular surveillance per GSD phenotype. [ABSTRACT FROM AUTHOR]

Abstract: In spina bifida aperta (SBA), spinal MRI provides a surrogate marker to estimate muscle damage caudal to the myelomeningocele (MMC). This muscle damage by the MMC can be quantified by intra-individual comparison of muscle ultrasound density (MUD) caudal versus cranial to the MMC (dMUD = [MUDcaudal-to-the-MMC] − [MUDcranial-to-the-MMC]). Quantitative dMUD assessment requires time, equipment and expertise, whereas it could also be visually determined by differences in muscle echodensity caudal vs. cranial to the MMC (visual-dMUD). If visual and quantitative dMUD correspond, visual dMUD assessment could provide a clinical screening parameter. In 100 SBA muscle ultrasound recordings of patients with various MMC levels, we aimed to compare quantitative dMUD (dMUD = [MUDcalf-muscle/S1] − [MUDquadriceps-muscle/L2-L4]) with visual dMUD assessments by 20 different observers. Results indicate that quantitative dMUD can be visually detected (sensitivity 86%; specificity 57%), implicating that visual dMUD screening could provide a quick, clinical screening tool for muscle impairment by the MMC. [Copyright &y& Elsevier]