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Background: The randomised double-blinded placebo-controlled EXIST-1–3 studies have showed everolimus effective with adverse effects reported as acceptable in treatment of symptoms in patients with tuberous sclerosis complex (TSC), although evidence of outcomes in clinical practice remains limited. This study aimed to investigate, in clinical practice, the effectiveness and safety of everolimus for epilepsy, renal angiomyolipoma (rAML), and subependymal giant cell astrocytoma (SEGA) in patients with TSC. Results: The study included 64 patients with TSC (median age: 19, range 0.9–54 years) receiving everolimus treatment (Norway: n = 35; Denmark: n = 29). Among 45 patients with epilepsy, 14 (31%) were responders experiencing ≥ 50% reduction in seizure frequency in the last 3 months of treatment compared with the last 3 months before treatment. Nineteen (42%) patients changed their anti-seizure medications (ASMs). Responders were more common among patients < 18 years (46%) than among patients ≥ 18 years (14%, p = 0.03). In 29 patients with rAML, everolimus reduced (≥ 30% decrease) and stabilized (< 20% increase, ≤ 30% decrease) longest diameter of rAML in 38% and 59%, respectively, after a mean treatment duration of 37 months. SEGA volume was reduced in three patients by 71%, 43%, and 48% after 39, 34, and 82 months. Adverse effects were reported in 61 of 64 patients (95%) after a median treatment duration of 31 months (range 0–106), with oral ulceration/stomatitis (63%) and upper respiratory tract infections (38%) being the most common. The most common laboratory abnormalities were increased cholesterol (41%), anaemia (30%), and leucopoenia (25%). Grade 3–4 adverse effects were reported in 36% of cases, and life-threatening conditions were reported in two patients. Nine patients discontinued everolimus treatment. Conclusions: Seizure reduction in this study sample was consistent with results from EXIST, but might be lower than expected, given that changes in concomitant ASMs are part of clinical practice. Seizure reduction was associated with younger age. As with EXIST, everolimus reduced or stabilised rAML size in most patients. SEGA volume was reduced in all three patients. Close follow-up is needed for this group, especially for children and patients who may not be able to report adverse effects. [ABSTRACT FROM AUTHOR]

Aim: To investigate how children with cerebral palsy (CP) perform in the Danish school system and which factors are associated with school performance. Method: This was a population‐based cohort study including 463 126 children born from 1997 to 2003. Data were extracted from seven national registries. The study encompassed 818 children with CP (483 [59.0%] males, 335 [41.0%] females) and 417 731 without CP (214 535 [51.4%] males, 203 196 [48.6%] females). We evaluated two primary outcomes: not completing 10 years of elementary school, defined as attending fewer than eight final mandatory exams; and grade point averages (GPAs). Mann–Whitney U tests were used to analyse differences in GPAs and logistic regressions were used to calculate odds ratios (ORs). Results: Among children with and without CP, 62.6% and 12.4% did not complete elementary school respectively (OR = 11.85 [10.28–13.66]). Additionally, children with CP who attended all final exams achieved lower overall GPAs than children without CP (6.6 vs 7.3, p = 0.001). In children with CP, comorbidities, maternal education, severity of motor impairments, and intellectual deficits were associated with increased odds of not completing elementary school. Notably, one‐third of children with CP with apparent normal intelligence did not complete school, despite special educational measures. Interpretation: Danish children with CP rarely complete elementary school despite initiatives for a more supportive educational system. The complexity of individual needs in children with CP may be challenging for an inclusive school environment. What this paper adds: Children with cerebral palsy (CP) have a high risk of not completing elementary school.Children with CP achieve lower overall grades than children without CP.Motor impairment, comorbidities, and maternal education are associated with poor school performance.Intellectual impairment is the most important predictor of poor school performance. What this paper adds: Children with cerebral palsy (CP) have a high risk of not completing elementary school.Children with CP achieve lower overall grades than children without CP.Motor impairment, comorbidities, and maternal education are associated with poor school performance.Intellectual impairment is the most important predictor of poor school performance. This original article is commented on by Lebeer on pages 1273–1274 of this issue. [ABSTRACT FROM AUTHOR]

Aim: To investigate reasons for the declining prevalence of cerebral palsy (CP) in children born at term in Denmark by evaluating obstetric and neonatal factors associated with CP, and their changes over time., Method: In this cohort study, we included 987 495 children (504 600 [51.1%] males and 482 895 [48.9%] females) born after 37 completed gestational weeks during birth years 1997 to 2013. Risk ratios of CP for each factor were calculated with log-binominal regression analyses. Significant factors were evaluated concerning their development in prevalence over time., Results: In the antenatal period, there were significant associations with an increased risk of CP and high maternal body mass index (BMI), smoking during pregnancy, nulliparity, male sex, gestational age, and low birthweight. In the study period, fewer females smoked during pregnancy and fewer children were born post-term, dropping from 22.6% to 11.4% and 9.4% to 2.5% respectively. Conversely, the proportion of females with high BMI increased. Most significant risk factors were found in the neonatal period, with an increase in children with diagnosed birth defects and children admitted to neonatal care., Interpretation: Reasons for the declining prevalence of CP appear to be multifactorial and likely include the decline in maternal smoking and children born post-term along with centralization and advances in neonatal treatment., (© 2021 Mac Keith Press.)

Aim: We aimed at describing clinical findings in children with dyskinetic as compared to bilateral spastic cerebral palsy (CP)., Methods: Data were extracted from the Danish nationwide CP register. Participants were born in 1999-2007 and were 5-6 years at ascertainment., Results: The total number of CP cases was 1165 of which 92 had dyskinetic and 540 bilateral spastic CP. Prevalence of dyskinetic CP was 0.16 per 1000 live births. In participants with dyskinetic compared to bilateral spastic CP, there was more frequently an Apgar level less than five at five minutes (22.7% vs. 11.2%) and neonatal seizures (43.5% vs. 28.5%), but less respiratory deficiency, hyperbilirubinaemia and sepsis. Impairment based on gross motor function classification was more severe in dyskinetic CP (level III-V 90.0% vs. 66.0%). In dyskinetic CP, there was a high rate of reduced developmental quotient (68.1%), visual impairment (39.3%) and epilepsy (51.6%). Basal ganglia lesions were more prevalent in dyskinetic compared to bilateral spastic CP (27.7% vs. 12.8%)., Conclusion: Cases of dyskinetic CP had overlapping clinical features with cases of bilateral spastic CP, but differed significantly in several perinatal risk factors. The children with dyskinetic CP had experienced more peri- or neonatal adverse events, and neurodevelopmental impairment was severe., (©2019 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Introduction: Epilepsy surgery is increasingly used to treat children with medically intractable epilepsy. This study investigates the aetiology and seizure outcome in Danish children operated between 1996 and 2010., Methods: Retrospectively collected data on structural magnetic resonance imaging (MRI) diagnoses, surgical procedures and seizure outcomes classified according to the Engel Classification were used. Changes over time grouped as 1996-2000, 2001-2005 and 2006-2010 were analysed., Results: A total of 95 children underwent epilepsy surgery. Sixty-three operations were performed in Denmark and 50 abroad. In all, 14 children needed reoperation. The median follow-up period was four years. At the latest follow-up, Engel class I (indicating no disabling seizures) was found in 67% of the patients. Cortical dysplasia, mesial temporal sclerosis and tumour were the most common MRI findings. The percentage of tumours operated decreased over time, and frontal lobe resections increased. In the 2006-2010 period, resections with normal MRI were performed, resulting in a less favourable Engel outcome. Persistent, unexpected complications were seen in three of 113 operations., Conclusions: The majority of children who undergo epilepsy surgery have a good, worthwhile seizure outcome. The seizure outcome for Danish children corresponds to that of other epilepsy surgery centres. The clinical criteria for selection of patients changed over time., Funding: none., Trial Registration: The Danish Data Protection Agency approved the project with record number: 2013-41-2459.

Alternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disorder characterized by early-onset recurrent distinctive hemiplegic episodes commonly accompanied by other paroxysmal features and developmental impairment. De novo mutations in ATP1A3 were recently identified as a genetic cause of AHC. To describe the entire Danish cohort of paediatric AHC patients we approached neuropaediatricians nationwide. All currently acknowledged Danish patients ≤16 years with AHC were genetically tested and seen by the same child neurologist (PU). Ten patients; seven girls and three boys were identified. Mean present age was 10.0 years (range 1-16). Mean age at presentation was 7.4 months (range 1-18 months). Sequencing of ATP1A3 in all ten patients revealed a pathogenic mutation in seven. Two females with moderate psychomotor impairment were heterozygous for the known p.G947R mutation, whereas one severely retarded boy was heterozygous for the common p.E815K mutation. The prevalent p.D801N mutation was identified in two moderate to severely retarded children. Interestingly, in a set of monochorionic male twins a novel p.D801E mutation was identified, underscoring that the asparagine at position 801 is a mutation hotspot. Three girls aged 5-13 years did not reveal any ATP1A3 mutations. They were rather mildly clinically affected and displayed a normal or near-normal psychomotor development. This is the first study of AHC in the Danish paediatric population. The patients harboured a wide range of psychomotor difficulties. Patients with no mutation detected tended to be less severely affected. Prevalence was approximately 1 per 100,000 children., (Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Carcinoma in situ (CIS) testis is the precursor stage for the majority of testicular germ cell tumours (TGCT). Infertility is one of the conditions known to predispose to TGCT, but based on scarce existing data, the prevalence of CIS in this risk group was estimated at only approximately 1%. To establish more objective data, we investigated retrospectively the prevalence of CIS based on testicular biopsies performed in a well-defined group of subfertile males. We included 453 patients who had testicular biopsies performed for infertility reasons during 1995-2005 at the Copenhagen University Hospital (Rigshospitalet). Biopsies were evaluated by two experienced observers independently. CIS was detected in 10 individuals, of whom three had bilateral CIS, corresponding to a prevalence of 2.2% (95% CI 1.1-4.0%). This is greater than the estimated risk of 0.45% for the age- and birth cohort-matched general Danish population. All patients with CIS testis had severe oligozoospermia (