Melatonin usage in children and young adults, a registry-based cohort study.

Sleep disorder is common in children and adolescents, particularly in those with attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD). While non-pharmacological treatment is first line, occasionally an add-on of an oral drug is needed. The endogenous hormone melatonin is increasingly used for sleep disorders in children and adolescents. In this registry-based cohort study we follow dispensation of melatonin in young individuals, 0-25 years of age, in Stockholm, Sweden during 2016-2019. In all 9980 individuals, were dispensed melatonin in 2016 and followed for 3 years. Child psychiatrist was the most common prescribing specialty, 55% of all prescriptions. Only 20% had a recorded diagnosis of sleep disorder. The majority, 65% had a neuro psychiatric diagnose. Half of the individuals had at least 4 prescribed drugs dispensed during the follow-up. Almost half of our cohort were dispensed melatonin during the entire study period and doses and volumes of drug dispensed increased by 50 and 100%, respectively. Continuous medication was most common among children 6-12 years, where 7 out of 10 individuals were still adherent after three years. As long-term safety data is lacking, we find this concerning, and this illustrates the need of long-term follow-up of melatonin use in children and young individuals.

Body surface area-based omega-3 fatty acids supplementation strongly correlates to blood concentrations in children.

Omega-3 fatty acids have been suggested as a complement in cancer treatment, but doses are not established. We performed a dose-finding study in 33 children in remission from cancer. Participants were allocated to a body surface area (BSA) adjusted dose (mg/m2) of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (40:60), ranging 233-3448 mg/m2 daily for 90 days. Fatty acid concentration in plasma phospholipids and red blood cells were determined by GC. Supplementation was well tolerated and correlated strongly with blood ω3-fatty acid concentrations and EPA showed the highest increase. Using the ω3-index disregards docosapentaenoic acid (DPA), which increased 30-43% in our study motivating an EDD-index (∑EPA,DPA,DHA). The ratio between arachidonic acid and EPA or DHA showed negative exponential trends. Dose per BSA enabled an individualized omega-3 supplementation decreasing the variation referred to interindividual differences. Based on our results, we suggest a dose of 1500 mg/m2 BSA for further studies.

Diffusion MRI in corticofugal fibers correlates with hand function in unilateral cerebral palsy.

UNLABELLED: Diffusion MRI improves detection of abnormalities in white matter tracts in cerebral palsy (CP). Relationships between diffusion measurements and hand function are largely unexplored. We aimed first to assess microstructure of corticofugal fibers, and second to explore associations between tract injury as assessed by quantitative analysis of diffusion MRI and hand function in children with unilateral CP. METHODS: In this cross-sectional study, 15 children with unilateral CP (6 boys, median age 12.4 years, min 7.2, max 17) and 24 controls were included (9 boys, median age 12.7 years, min 8.8, max 17.3). Hand function was assessed with the Box and Blocks (B&B) test. Magnetic resonance diffusion data (b value = 1,000 s/mm(2), 45 directions) were collected on a 1.5-T scanner. Fractional anisotropy (FA), mean diffusivity (MD), and tensor eigenvalues were measured bilaterally in the cerebral peduncle (ROI1), the posterior limb of the internal capsule (PLIC, ROI2), and corticofugal fibers connecting these regions. RESULTS: In children with CP, FA in both ROIs and the partial tract corresponding to the affected hand was significantly lower compared to controls. This was caused by an increase in diffusivity perpendicular to the tract. After controlling for age, mean FA contralateral to the affected hand correlated with B&B scores, which was independent of lesion type or number of voxels in the partial tract, cerebral peduncle, or PLIC. CONCLUSIONS: FA in corticofugal fibers is a sensitive marker of damage to the motor system and correlates with hand function in CP. Using FA may improve early prediction of outcome.

Botulinum toxin A treatment in toddlers with cerebral palsy.

AIMS: In this study the aim was to evaluate the effect of botulinum toxin A (BoNT-A) treatment on muscle tone, contracture development and gait pattern in young children with cerebral palsy (CP). METHOD: Fifteen children with spastic CP (mean age = 16 months) were included in a randomized control study. All received a daily stretching programme and children in the BoNT-A group additionally received two injections, 6 months apart in the gastrocnemius muscle. Outcomes were assessed at baseline, and after 1 and 3.5 years. A 3D gait-analysis was performed at 5 years of age. RESULTS: Plantarflexor muscle tone in the BoNT-A group was significantly reduced after 3.5 years, while the muscle tone at the ankle and knee in the control group remained unchanged. The change-score in knee-flexion muscle tone between the groups was significantly different after 3.5 years. The knee joint ROM was significantly increased at 1 year in the BoNT-A group but reduced at the knee and ankle joints in the control group after 3.5 years. No group differences were found for gait analysis, GMFM-66 or PEDI. CONCLUSION: Early treatment of BoNT-A in children with spastic CP may decrease muscle tone and decelerate contracture development after 3.5 years. The effect on gait development remains inconclusive.

Centrotemporal spikes in families with rolandic epilepsy: linkage to chromosome 15q14.

OBJECTIVE: To localize a gene predisposing to benign epilepsy of childhood with centrotemporal spikes (BECTS). BACKGROUND: BECTS, or rolandic epilepsy, is the most prevalent idiopathic epilepsy syndrome in childhood. Functional relevant defects in the alpha 4 subunit of the neuronal nicotinic acetylcholine receptor (AChR) have been demonstrated in autosomal dominant nocturnal frontal lobe epilepsy, which, like BECTS, is an idiopathic partial epilepsy. METHODS: A DNA linkage study was conducted screening all chromosomal regions known to harbor neuronal nicotinic AChR subunit genes. Twenty-two nuclear families with BECTS were analyzed. RESULTS: In an "affected-only" study, best p values and lod scores were reached between D15S165 and D15S1010 on chromosome 15q14. In multipoint nonparametric linkage analysis a nominal p value of 0.000494 was calculated by GENEHUNTER. Best parametric results were obtained under an autosomal recessive model with heterogeneity (multipoint lod score 3.56 with 70% of families linked to the locus). These markers are localized in direct vicinity to the alpha 7 subunit gene of the AChR. CONCLUSIONS: We found evidence for linkage of BECTS to a region on chromosome 15q14. Either the alpha 7 AChR subunit gene or a closely linked gene are implicated in pedigrees with BECTS. The disorder is genetically heterogeneous. Surprisingly, the same chromosomal area has been reported to be linked to the phenotype in families with an auditory neurophysiologic deficit as well as in families with juvenile myoclonic epilepsy, another idiopathic but generalized epilepsy syndrome.