Journal of Child Neurology

Fragile X syndrome (FXS), the most common monogenic cause of intellectual disability and autism spectrum disorder, has been one of the first neurodevelopmental disorders in which molecular and neuronal mechanisms of disease were identified, leading to the concept of targeting the underlying disease to reverse symptoms. Translating findings in basic science and animal models to humans with FXS has proven difficult. These challenges have prompted the FXS field to organize to build interlocking projects and initiatives to improve consistency of supportive care, make clinical research accessible to families, generate collaborative research on natural history, outcome measures and biomarkers, and create clinical trial consortia and novel trial designs. This work has resulted in improved success in recent clinical trials, providing key steps toward regulatory approval of disease-targeted treatments for FXS. Progress in the FXS field has informed translation of transformative new disease-targeted therapies for other monogenic neurodevelopmental disorders.

Deep brain stimulation (DBS) is an established intervention for use in pediatric movement disorders, especially dystonia. Although multiple publications have provided guidelines for deep brain stimulation patient selection and programming in adults, there are no evidence-based or consensus statements published for pediatrics. The result is lack of standardized care and underutilization of this effective treatment. To this end, we assembled a focus group of 13 pediatric movement disorder specialists and 1 neurosurgeon experienced in pediatric deep brain stimulation to review recent literature and current practices and propose a standardized approach to candidate selection, implantation target site selection, and programming algorithms. For pediatric dystonia, we provide algorithms for (1) programming for initial session and follow-up sessions, and (2) troubleshooting side effects encountered during programming. We discuss common side effects, how they present, and recommendations for management. This topical review serves as a resource for movement disorders specialists interested in using deep brain stimulation for pediatric dystonia.

Introduction: Cluster headache is rare in children and only a few clinical studies have systematically evaluated cluster headache in children. Methods: This study was conducted between August 2019 and December 2021 with the primary aim to evaluate the feasibility and utility of the Cluster Headache Severity Scale in determining the severity of cluster headache in patients aged less than 18 years and monitoring response to prescribed treatment. Secondary objectives were to evaluate the feasibility and utility of Cluster Headache Quality of Life, Cluster Headache Index, and 6-item Headache Impact Test in pediatric cluster headache patients to assess the quality of life, severity, and impact of cluster headache. Results: A total of 32 children (age of onset 11.9 ± 2.3 years, age of diagnosis 13.7 ± 2.4 years, 68% boys) were enrolled. Although 30 cases had their headache episodes occurring during nighttime, only 16 children had a Children’s Sleep Habits Questionnaire (CSHQ) score >41 at baseline. All children responded to prednisolone as bridging therapy and 23 of 32 showed adequate pain relief after sumatriptan nasal spray for an acute attack. The average time taken for completion of Cluster Headache Index, Cluster Headache Severity Scale, Cluster Headache Quality of Life, and Headache Impact Test–6 scores were 5.2 ± 0.7, 5.1 ± 0.8, 27.4 ± 3.5, and 6.2 ± 0.8 minutes, respectively. The interrater reliability was good for Cluster Headache Severity Scale, Cluster Headache Quality of Life, and Headache Impact Test–6 (Cronbach α 0.93, 0.81, and 0.89, respectively). There was a strong positive correlation between the Cluster Headache Severity Scale score with Headache Impact Test–6 score and Cluster Headache Quality of Life score (correlation coefficient r = 0.90 and 0.98). Conclusion: Majority of pediatric cluster headache patients are likely to respond to prednisolone and sumatriptan. Cluster Headache Severity Scale, Cluster Headache Quality of Life, and Headache Impact Test–6 can be used for pediatric cluster headache patients for treatment monitoring.

Background:There is still a need for more studies to evaluate the role of vitamin D₃ in pediatric migraine prophylaxis. Objectives: We aimed to evaluate the effects and safety of vitamin D₃ supplementation to topiramate on pediatric migraine. Methods: A double-blinded prospective clinical trial was conducted on 5- to 14-year-old children with migraine. They were randomly assigned in a 1:1 ratio into 2 groups, one with vitamin D₃ supplementation (the supplementation group) and the other without vitamin D supplementation (the placebo group). The supplementation group received topiramate plus one 5000-IU dose of vitamin D₃ daily for 4 months. The placebo group received topiramate with a placebo capsule without any effective substances. The primary outcomes were a monthly frequency of headache attacks, a good response to intervention, and reduction in migraine severity, duration, and disability before and after treatment. Fifty-six children completed the trial. Vitamin D₃ supplementation to topiramate was more effective than the placebo group in the reduction of monthly frequency (6231.31 vs 9792.24 times, P = .01) and disability score for migraines (17 566.43 vs 25 187.65, P = .04). A good response was observed in 76.13% of patients in the vitamin D₃ supplementation group and 53.5% of patients in the placebo group, and vitamin D₃ supplementation was significantly more effective than placebo (P = .01). Side effects were observed in 13.3% and 20% of the intervention group and placebo groups, respectively, P = .5. Conclusion: Vitamin D₃ supplementation in pediatric migraine prophylaxis could be a well-tolerated, safe, and effective strategy.

This study investigated the experiences of 25 caregivers of children with early-onset, treatment-resistant epilepsy who pursued whole exome sequencing to determine the impact of the test results on their child’s treatment. Caregivers who consented to be recontacted were recruited from a previous study investigating the diagnostic yield of whole exome sequencing. A semistructured interview addressed questions based on one of 2 study phases. The first phase discussed the decision-making process for genetic testing (15 interviews), which revealed 4 major themes: (1) prognosis, (2) engagement, (3) concerns, and (4) autonomy. The second phase discussed the impact of genetic testing on treatment (10 interviews), which revealed 3 major themes: (1) testing features, (2) emotional impact, and (3) treatment outcomes. Overall, parents pursued genetic testing to obtain a clear prognosis, inform treatment decisions, engage with other families, and exercise autonomy. Caregivers felt that early testing is warranted to inform their child’s diagnostic odyssey.

Background: Administration of the Einstein Neonatal Neurobehavioral Assessment Scale (ENNAS) can be time-consuming, and items can be highly correlated. We aimed to determine: (1) its factor analytic structure; (2) the validity of the factor structure; and (3) the associations of physiologic measures with factor scores. Methods: A factor analysis reduced 21 ENNAS items into 5 factors in 57 congenital heart disease (CHD) and 35 healthy infants. Multiple linear regressions examined the association of factor scores with group, gestational age, and physiologic variables. Results: 5-factor solution: 1 (Orienting Reflex), 2 (Extensor Axial Tone), 3 (Primitive Reflexes), 4 (Flexor Tone), 5 (Reflexive Tone Around Extremity Joints). Moderate to strong evidence supported: face, discriminant, and construct validity of these factors, with Factor 2 having the strongest. Conclusions: Components of Factor 2 may provide similar information about neonatal development, thus reducing the time for and burden of administration for researchers and clinicians.

Introduction: The prevalence and patterns of sleep disturbances in neurocutaneous syndromes are variable and understudied. Methods: Cross-sectional study for 18 months at a tertiary care pediatric hospital, involving 100 children with neurocutaneous syndromes aged between 4 and 10 years using the Children's Sleep Habits Questionnaire-Abbreviated. Results: In 100 children with neurocutaneous syndromes, 47 (47%) had significant sleep problems. In subgroup analysis, 7 of 17 children with neurofibromatosis 1, 24 of 63 children with tuberous sclerosis complex, 10 of 12 children with Sturge-Weber syndrome, 2 of 3 children with linear nevus sebaceous syndrome, and each of the children with hypomelanosis of Ito, McCune-Albright syndrome, megalencephaly-capillary malformation syndrome, and unclassified neurocutaneous syndrome had significant sleep problems. Conclusion: The prevalence of sleep problems in our study population was not more than that observed in the general pediatric population. Prospective multicentric studies are needed to comprehend sleep problems in children with neurocutaneous syndromes.

Background: Younger stroke patients may suffer worse outcomes than older patients; however, the extent to which age at stroke impacts remote areas of the brain remains unclear. The objective of this study was to determine thalamic volume changes ipsilateral to middle cerebral artery territory strokes based on age at acute ischemic stroke onset. Methods: Acute ischemic stroke patients <9 years, 9-18 years, and >18 years old were retrospectively recruited from a large quaternary care system. Each subject underwent an acute (<72 hours from AIS) and chronic (>90 days) magnetic resonance imaging (MRI) scan. Manual thalamic segmentation was performed. Results: Younger and older children had significantly greater stroke-side thalamic volume loss compared to adults (48.2%, P = .022; 40.7%, P = .044, respectively). Conclusions: Stroke-side thalamic volumes decreased across the age spectrum but to a greater degree in pediatric patients. This observation can affect functional and cognitive outcomes post stroke and warrants further research.