Distinct Magnetic Resonance Imaging in a Child With a TACO1 Variant.

This case report describes a unique magnetic resonance imaging result in a young boy with a TACO1 variant.

Zoledronate Increases Bone Mineral Density in Nonambulant Children With Cerebral Palsy: A Randomized Controlled Trial.

CONTEXT: Zoledronate appears to reduce fracture rates in children with cerebral palsy (CP), but no previous randomized, controlled trial has been performed to compare the effect of zoledronate to placebo in children with CP. OBJECTIVE: To investigate the effect of zoledronate on bone mineral density (BMD) Z-scores in children with nonambulant CP in a randomized, controlled, double-blind trial. METHODS: Nonambulant children with CP (5 to 16 years of age) were randomized 1:1 to receive 2 doses of zoledronate or placebo at a 6-month interval. BMD Z-score changes at the lumbar spine and the lateral distal femur (LDF) were calculated from dual-energy x-ray absorptiometry scans. Monitoring included weight, bone age, pubertal staging, knee-heel length, adverse events, biochemical markers, and questionnaires. RESULTS: Twenty-four participants were randomized and all completed the study. Fourteen were assigned to zoledronate. The mean lumbar spine BMD Z-score increased 0.8 SD (95% CI: 0.4; 1.2) in the zoledronate group, which was significant when compared to 0.0 SD (95% CI: -0.3; 0.3) in the placebo group. Similarly, the LDF BMD Z-scores increased more in the zoledronate group. Severe acute phase symptoms affected 50% of the patients in the zoledronate group but were reported exclusively after the first dose. Growth parameters were similar in both groups. CONCLUSION: Zoledronate for 12 months increased BMD Z-scores significantly without affecting growth, but first-dose side effects were common and considerable. Studies into lower first doses and long-term outcomes are needed.

Cerebral palsy and bisphosphonates - and what can be learned from other types of secondary osteoporosis in children: A scoping review.

AIM: We aimed to improve bone health management of children with cerebral palsy (CP) by reviewing studies investigating bisphosphonate therapy in children with CP and other types of secondary osteoporosis. METHODS: We included trials on bisphosphonate treatment reporting any direct bone measurement or fracture outcome. All studies of patients with CP were included. We also included all controlled trials of children with secondary bone fragility as well as observational studies with ≥20 participants or at least 3 years of follow-up. Studies were assessed according to PRISMA guidelines using the RoB2-tool and the Newcastle-Ottawa Scale. RESULTS: We reviewed 1104 studies and found 37 eligible. Some studies were sufficiently homogeneous to include in a meta-analysis, and we found a 1-year effect on lumbar spine bone mineral density (BMD) Z-score of +0.65 after oral and + 1.21 after intravenous bisphosphonates in children with secondary osteoporosis. Further, data on adverse events and post-treatment follow-up were reviewed. Limitations were heterogeneity and small size of the included studies. CONCLUSION: Meta-analysis consistently showed significant BMD increases with bisphosphonates in children with secondary osteoporosis. Direct evidence of the effect of bisphosphonates on reducing fractures is lacking. We found no reports of long-term adverse events yet longer studies are needed.

Fracture Rates in Children with Cerebral Palsy: A Danish, Nationwide Register-Based Study.

Background: In children with cerebral palsy (CP), fracture rates have been reported to be higher than in the general population but age-specific fracture rates have not been directly compared and the effect of comorbid epilepsy needs elucidation. This impairs decision-making regarding bone health interventions. Aim: We aimed to establish the age-specific fracture rates in children with CP with and without epilepsy in Denmark. Materials and Methods: Data from Danish registers were combined to establish cohorts of children with and without CP born in Denmark from 1997 to 2007. Fracture rates were calculated for 1997-2016. Results: We identified 1,451 children with CP and 787,159 without CP. Female/male fracture rates per 1,000 person-years were 23/27 with CP and 23/29 without CP. Male sex, epilepsy and anti-seizure medication, but not the diagnosis of CP or GMFCS-level, were associated with higher fracture rates. Relatively more lower extremity fractures occurred in non-ambulant children with CP. Interpretation/Conclusion: We found no increased fracture rates in children with CP when compared to peers; however, fracture locations suggested bone fragility in non-ambulant children. All children with epilepsy and on anti-seizure medication had increased fracture rates. We suggest bone health optimization in these groups.

Autosomal dominant sleep-related hypermotor epilepsy caused by a previously unreported CHRNA4 variant.

Autosomal dominant sleep-related hypermotor epilepsy (ADSHE) is a rare heritable form of epilepsy. It is characterized by hypermotor seizures occurring mainly during sleep. Seizures are typically abrupt in onset and offset and tend to increase in complexity and duration during the night. ADSHE is inherited in an autosomal dominant manner, and penetrance is estimated to be 70%. We describe two brothers with ADSHE with a previously unreported variant in CHRNA4, and the effect of medical treatment with carbamazepine. We highlight the relevance of genetic testing in patients with atypical and clustering episodes of nightmares, night terrors, or panic attacks, as these patients could be misdiagnosed, and instead be suffering from ADSHE, a potentially treatable condition.

Predictors for early diagnosis of cerebral palsy from national registry data.

AIM: As early intervention is important in cerebral palsy (CP), an early diagnosis is desirable. The aim of this study was to establish the median diagnostic age of CP and to identify predictors of an early diagnosis in a population-based cohort. METHOD: Using the Danish National Cerebral Palsy Registry (NCPR), we identified 1291 children with CP (764 males, 527 females) born between 1995 and 2003. The date of diagnosis was defined as the day the parents were told that their child was spastic or had CP. We calculated the age of diagnosis and analysed the following predictors: type of CP, degree of motor disability, cerebral ultrasonography results, epilepsy, gestational age, and degree of cognitive impairment. RESULTS: We found the overall median corrected diagnostic age of CP to be 11 months. Early diagnosis was associated with the type of CP, presence of epilepsy, a high degree of motor disability, and abnormalities in the cerebral ultrasonography. The gestational age was not associated with the diagnostic age. INTERPRETATION: The median diagnostic age implies that half of the Danish children with CP will be able to enter an early intervention program before 1 year of age. A late diagnosis was associated with less severe symptoms, and gestational age did not influence the diagnostic age.

[Urine samples from children collected in their homes]. / Børneurinprøver indsamlet i hjemmet.

INTRODUCTION: Children at high risk of urinary tract infection (UTI) enter a programme for domestic urine sampling at the Paediatric Department in Aarhus. Parents collect urine, describe symptoms and post the samples. We wanted to determine the value of domestic urine sampling and to evaluate the programme. MATERIAL AND METHODS: All samples received in 2004 were studied. RESULTS: A total of 706 urine samples from children in the programme were cultivated. In all 76 children fulfilled the criteria for UTI when culture and symptoms were compared. Dip-slide analysis had a sensitivity of 72% and a negative predictive value of 96%. A total of 329 urine samples with negative dip-slide analyses were collected from children with no urinary tract symptoms. Only 27 of these samples were culture-positive and none of these children developed signs of UTI. CONCLUSION: The results from this study suggest that home urine sampling from children at high risk of UTI with no symptoms does not contribute towards avoiding the development of pyelonephritis. A home urine sample analysis programme for children with symptoms is, however, a valuable instrument for early and efficient treatment of UTI in children with high risk of UTI. Urine samples should only be cultivated if the child has symptoms or the dip-slide test is positive.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy resulting in stroke in an 11-year-old male.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the Notch3 gene on chromosome 19. The condition manifests itself clinically typically in the third to fifth decade with migraine and recurrent episodes of stroke or transient ischaemic attacks. We report the case of an 11-year-old male with CADASIL resulting in stroke with right hemiparesis and dysphasia. Acute magnetic resonance imaging suggested infarction in the left hemisphere; magnetic resonance angiography revealed calibre variation of the intracerebral arteries. The patient suffered from common migraine with five to six attacks per month for 3 years 6 months before the stroke. Attacks occurred early in the morning with severe one-sided headache, photophobia, nausea, and vomiting. Antimigraine medications had no effect. The family history revealed more cases of CADASIL, with an autosomal dominant pattern. The diagnosis of CADASIL was confirmed by the finding of the known mutation of the Notch3 gene running in the family. With treatment in a neurorehabilitation centre the patient recovered most of his functions with only discrete fine-motor and cognitive sequelae. Our case report highlights the need for paediatricians to consider CADASIL in childhood stroke as well as in migraine patients.