Current state of hemispherectomy and callosotomy for pediatric refractory epilepsy in Denmark.

OBJECTIVE: To evaluate outcomes from hemispherectomy and callosotomy related to the need for anti-seizure medication (ASM), seizure frequency, and cognition. METHODS: A review of the medical charts of all Danish pediatric patients who underwent hemispherectomy or callosotomy from January 1996 to December 2019 for preoperative and postoperative ASM use, seizure frequency, and cognitive data. RESULTS: The median age of epilepsy onset was two years (interquartile range (IQR): 0.0-5.3) for the hemispherectomy patients (n = 16) and one year (IQR: 0.6-1.7) for callosotomy patients (n = 5). Median time from onset to final surgery was 3.4 years for hemispherectomy and 10.2 years for callosotomy, while the median follow-up time was 6.9 years and 9.0 years, respectively. Preoperatively, all patients had daily seizures and were treated with ≥ 2 ASM. Hemispherectomy resulted in a reduction in seizure frequency in 87.5 % of patients, with 78.6 % achieving seizure freedom. Furthermore, 81.3 % experienced a reduction in ASM use and 56.3 % stopped all ASM. Median IQ/developmental quotient (IQ/DQ) was low preoperatively (44.0 [IQR: 40.0-55.0]) and remained unchanged postoperatively (IQ change: 0.0 [IQR: -10.0-+4.0]). Callosotomy resulted in a seizure reduction of 86-99 % in four patients, and ASM could be reduced in three patients. Median IQ/DQ was 20.0 preoperatively (IQR: 20.0-30.0) and remained unchanged postoperatively (IQ change: 0.0 [IQR: 0.0]). CONCLUSION: Hemispherectomy and callosotomy result in a substantial reduction in seizure frequency and ASM use without deterioration of IQ. Extensive epilepsy surgery should be considered early in children with drug-resistant epilepsy.

School performance and psychiatric comorbidity in childhood absence epilepsy: A Danish cohort study.

The aim was to determine school performance and psychiatric comorbidity in children with childhood absence epilepsy (CAE). We reviewed the medical records in children with ICD-10 codes for idiopathic generalized epilepsy before 18 years of age, and pediatric neurologists confirmed the International League Against Epilepsy criteria for CAE were met. Control groups were the general pediatric population or children with non-neurological chronic disease. Outcomes were from nationwide and population-based registers on school performance and psychiatric comorbidity. We compared the mean grade point average using linear regression and estimated hazard ratios (HR) using Cox regression for the other outcomes. Analyses were adjusted for the child's sex, and year of birth, and parental highest education, receipt of cash benefits or early disability pension. We included 114 children with CAE with a median age at onset of 5.9 years (interquartile range = 4.5-7.3 years). Compared with both population controls and non-neurological chronically ill children, children with CAE had increased hazard of special needs education (HR = 2.7, 95% confidence interval (CI) = 1.8-4.1, p < 0.0001), lower grade point average at 9th grade by 1.7 grade points (95% CI = -2.5 to -1.0, p < 0.001), increased ADHD medicine use (HR = 4.4, 95% CI = 2.7-7.2, p < 0.001), increased sleep medicine use (HR = 2.7, 95% CI = 1.7-4.3, p < 0.001), and increased psychiatry visits (HR = 2.1, 95% CI = 1.1-4.0, p = 0.03). In conclusion, children with CAE have increased psychiatric comorbidity and a considerable proportion of these children receive special needs education in primary/secondary school, albeit insufficient to normalize their considerably lower grade point average in the 9th grade.

School performance and psychiatric comorbidity in juvenile absence epilepsy and juvenile myoclonic epilepsy: a Danish population-based cohort study.

BACKGROUND: We aimed to determine school performance and psychiatric comorbidity in juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and generalized tonic-clonic seizures (GTCS) alone. METHODS: All children (< 18 years) fulfilled International League Against Epilepsy criteria after review of their medical records. Control groups were the pediatric background population or children with non-neurological chronic disease. Outcomes were on school performance and psychiatric comorbidity. We compared mean grade point averages using linear regression and estimated hazard ratios using Cox regression in the remaining analyses. We adjusted for the child's sex, age, and year of birth; and parental highest education, receipt of cash benefits or early retirement. RESULTS: We included 92 JAE, 190 JME, 27 GTCS alone, 15,084 non-neurological chronic disease controls, and population controls. JAE had two times increased hazard for special needs education compared with age-matched population controls (hazard ratio 2.2, 95% CI = 1.1‒4.6, p = 0.03); this was not seen in JME. Compared with population controls, both JAE and JME had lower grade point average in secondary and high school (JME: 9th grade: - 0.5 points, 95% CI = -0.9 to -0.06, p = 0.03; high school: - 0.6 points, 95% CI = -1.3 to -0.1, p = 0.04), and 8% fewer JME and 15% fewer JAE attended high school. Both JME and JAE had higher hazard for redeeming sleep medication compared with non-neurological chronic disease; additionally, JAE had increased hazard for ADHD medicine redemptions. CONCLUSIONS: Both JAE and JME had marginally poorer school performance; performance seemed worse in JAE than in JME. Both JAE and JME had increased use of sleep medication.

Validation of Pediatric Idiopathic Generalized Epilepsy Diagnoses from the Danish National Patient Register During 1994‒2019.

Objective: To identify pediatric idiopathic generalized epilepsy (IGE) during 1994-2019 using ICD-10 codes in the Danish National Patient Register and anti-seizure prescriptions in the Danish Prescription Database. Study Design and Setting: We reviewed the medical records in children with ICD-10 codes for IGE before 18 years of age, and pediatric neurologists confirmed that the International League Against Epilepsy criteria were met. We estimated positive predictive values (PPV) and sensitivity for ICD-10 alone, including combinations of codes, anti-seizure prescription, and age at first code registration using medical record-validated diagnoses as gold standard. Results: We validated the medical record in 969 children with an ICD-10 code of IGE, and 431 children had IGE (115 childhood absence epilepsy, 97 juvenile absence epilepsy, 192 juvenile myoclonic epilepsy, 27 generalized tonic-clonic seizures alone). By combining ICD-10 codes with antiseizure prescription and age at epilepsy code registration, we found a PPV for childhood absence epilepsy at 44% (95% confidence interval [CI]=34%‒54%) and for juvenile absence epilepsy at 44% (95% CI=36%-52%). However, ethosuximide prescription, age at ethosuximide code registration before age 8 years and a combination of ICD-10 codes yielded a PPV of 59% (95% CI=42%‒75%) for childhood absence epilepsy but the sensitivity was only 17% (20/115 children identified). For juvenile myoclonic epilepsy the highest PPV was 68% (95% CI=62%‒74%) using the code G40.3F plus antiseizure prescription and age at epilepsy code registration after age 8 years, with sensitivity of 85% (164/192 children identified). For generalized tonic-clonic seizures alone the highest PPV was 31% (95% CI=15%‒51%) using G40.3G during 2006-2019 plus antiseizure prescription and age at code registration after age 5 years. Conclusion: The Danish National Patient Register and the Danish Prescription Database are not suitable for identifying children with IGE subtypes, except for juvenile myoclonic epilepsy which can be identified with caution.

First-trimester biomarkers and the risk of cerebral palsy.

BACKGROUND: Cerebral palsy (CP) is the most common severe motor disability and a manifestation of early brain damage. AIMS: To analyze if abnormal levels of first-trimester biomarkers were associated with CP. Furthermore, to investigate their clinical applicability in early predicting of CP. STUDY DESIGN: Nationwide cohort study. SUBJECTS: We included 258.057 singleton live births, born during 2008-2013 with completed first-trimester assessments. OUTCOME MEASURES: Data on beta subunit of human chorionic gonadotropin (beta-hCG), pregnancy-associated plasma protein-A (PAPP-A), nuchal translucency thickness, and biparietal diameter (BPD) were converted to multiple of the medians (MoM). Associations were analyzed by comparing mean and extreme levels between pregnancies with and without CP. All CP diagnoses were validated by trained neuropediatricians. Logistic regression was used to create an early prediction model. RESULTS: The mean beta-hCG value was significantly lower in pregnancies with CP (0.96MoM [95% CI 0.91-1.02] vs 1.04MoM [1.04-1.04], p = 0.01) and the mean PAPP-A value tended to be lower (0.96MoM [0.91-1.01] vs 1.01MoM [1.00-1.01], p = 0.07). Moreover, fetuses that developed CP more likely had a BPD measurement below the fifth percentile (7.5% vs 5%, p = 0.045). The final prediction model had poor discrimination. CONCLUSIONS: Pregnancies with CP tend to have lower values of beta-hCG and PAPP-A in the first trimester, however, the associations are mediated differently. Nonetheless, abnormal levels of the most common first-trimester biomarkers only have weak associations with CP; resulting in inadequate predictive abilities when included in an early prediction model.

Employment, health visits, mental health, and mortality in parents with a chronically ill child: a Danish nationwide population-based cohort study.

Chronic diseases in children can impact their parents; this may be overlooked in a clinical setting. Our aim was to investigate associations of chronic diseases in children with their parents' employment, health care utilization, mental health, and mortality. In a matched cohort study using nationwide and population-based data in Denmark, we included parents to children (< 18 years) with acute disseminated encephalomyelitis, multiple sclerosis, type 1 diabetes, inflammatory bowel disease, and rheumatoid arthritis/juvenile idiopathic arthritis during 2008-2015. The reference group was parents to unaffected children. Outcomes were parental employment (early retirement, cash benefits, income), health care utilization (e.g., general practitioner, or hospital visits), mental health (visits to psychiatry/psychology clinics, antidepressant drug redemptions), and mortality. We included 13,769 parents with a chronically ill child and 138,606 control parents. Annual income was unaffected for two-parent families after the child's disease onset, but two-parent families had increased hazard of early retirement of 25% (95% CI = 1.01-1.54; p = 0.04). Parents with a chronically ill child had (a) increased rate of antidepressant drug redemptions or psychology/psychiatry visits (hazard ratio 1.37; 95% CI = 1.28-1.46 at 1-year follow-up); (b) increased health care utilization, with an increased marginal mean in primary care of 1% (95% CI = 1.00-1.02; p = 0.005), hospital-affiliated visits of 19% (95% CI = 1.14-1.24; p < 0.0001), and hospital admissions of 14% (95% CI = 1.09-1.20; p < 0.0001); and (c) 69% increased mortality hazard (95% CI = 1.30-2.18; p < 0.0001) in parents younger than 50 years with no comorbidities, albeit small in absolute numbers. CONCLUSION: Pediatric chronic diseases were negatively associated with parental employment, mental health, and mortality, and increased health care utilization. WHAT IS KNOWN: • Studies on the impact of pediatric chronic diseases on parental health are qualitative. • Knowledge is unavailable regarding the impact on parental work, health care utilization, and mortality. WHAT IS NEW: • Among 13,769 parents with a chronically ill child and 138,606 control parents, parents with a chronically ill child had 37% increased antidepressant drug redemptions, and these parents <50 years without comorbidities had 69% increased mortality hazard. • Medical doctors should consider the parental health condition and societal challenges related to having child with a chronic disease.

Glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with differences in uncinate fasciculus microstructure.

BACKGROUND: Evidence suggests that fronto-limbic brain regions and connecting white matter fibre tracts in the left hemisphere are more sensitive to glucocorticoids than in the right hemisphere. It is unknown whether treatment with glucocorticoids in childhood is associated with microstructural differences of the uncinate fasciculus and cingulum bundle, which connect fronto-limbic brain regions. Here, we tested the hypothesis that prior glucocorticoid treatment would be associated with differences in fractional anisotropy (FA) of the left relative to right uncinate fasciculus and cingulum bundle. METHODS: We performed diffusion-weighted imaging in 28 children and adolescents aged 7-16 years previously treated with glucocorticoids for nephrotic syndrome or rheumatic disease and 28 healthy controls. RESULTS: Patients displayed significantly different asymmetry in the microstructure of uncinate fasciculus with higher left but similar right uncinate fasciculus FA and axial diffusivity compared to controls. No apparent differences were observed for the cingulum. Notably, higher cumulative glucocorticoid doses were significantly associated with higher uncinate fasciculus FA and axial diffusivity bilaterally. CONCLUSIONS: Our findings indicate that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in the microstructure of the uncinate fasciculi, and that higher cumulative glucocorticoid doses have a proportional impact on the microstructure. IMPACT: It is unknown if treatment with glucocorticoids in childhood have long-term effects on fronto-limbic white matter microstructure. The study examined if children and adolescents previously treated with glucocorticoids for nephrotic syndrome or rheumatic disorder differed in fronto-limbic white matter microstructure compared to healthy controls. The nephrotic and rheumatic patients had higher left but similar right uncinate fasciculus FA and axial diffusivity. Higher bilateral uncinate fasciculus FA and axial diffusivity was associated with higher cumulative glucocorticoid doses. We revealed new evidence suggesting that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in uncinate fasciculi microstructure.

Maternal intake of folate during pregnancy and risk of cerebral palsy in the MOBAND-CP cohort.

BACKGROUND: Folate prevents neural tube defects and may play a role in some neurodevelopmental disorders. OBJECTIVES: We investigated whether higher intakes of periconceptional or midpregnancy folate, as recommended, were associated with a reduced risk of offspring cerebral palsy (CP). METHODS: We included participants from the Nordic collaboration cohort consisting of mother-child dyads in the Danish National Birth Cohort and the Norwegian Mother, Father, and Child Cohort Study [combined as MOthers and BAbies in Norway and Denmark (MOBAND-CP)]. A total of 190,989 live-born children surviving the first year of life were included. Missing covariate data were multiply imputed. Our exposures were defined as any or no folic acid supplementation in gestational weeks (GWs) -4 to 8 (periconceptional), 9 to 12, and -4 to 12, and supplemental, dietary, and total folate during midpregnancy (GWs 22-25). CP overall and the unilateral and bilateral spastic subtypes, as well as CP with low or moderate/high gross motor function impairments, were our outcomes of interest. RESULTS: Periconceptional folic acid supplementation was not associated with CP [adjusted odds ratio (aOR), 1.02; 95% CI: 0.82-1.28]. However, supplementation in GWs 9 to 12 was associated with a reduced risk of CP (aOR, 0.74; 95% CI: 0.57-0.96), and inverse associations were indicated for both the unilateral (aOR, 0.68; 95% CI: 0.46-1.02) and bilateral (aOR, 0.70; 95% CI: 0.49-1.02) spastic subtypes, although the associations were not statistically significant. Supplemental or dietary folate in midpregnancy alone were not associated with CP. Strong inverse associations were observed with low gross motor function impairment (aOR, 0.49; 95% CI: 0.29-0.83), while for unilateral CP the aOR was 0.63 (95% CI: 0.34-1.22) for intakes of ≥500 compared to ≤199 dietary folate equivalents/day during midpregnancy. CONCLUSIONS: Our findings suggest that folate intakes in GWs 9 to 12 and midpregnancy were associated with lower risks of CP, while no association was observed for periconceptional supplementation.

Using both electromyography and movement disorder assessment improved the classification of children with dyskinetic cerebral palsy.

AIM: Children with dyskinetic cerebral palsy (CP) are often severely affected and effective treatment is difficult, due to different underlying disease mechanisms. Comprehensive systematic movement disorder evaluations were carried out on patients with this disorder. METHODS: Patients born from 1995 to 2007 were identified from the Danish Cerebral Palsy Register and referrals to the neuropaediatric centre, Rigshospitalet, Copenhagen. They were classified by gross motor function, manual functional ability, communication ability, dystonia and spasticity. Electromyography was carried out on the upper and lower limbs. Magnetic resonance imaging scans were revised, and aetiological searches for underlying genetic disorders were performed. RESULTS: We investigated 25 patients with dyskinetic CP at a mean age of 11.7 years. Dystonia, spasticity and rigidity were found in the upper limbs of 21, four and six children, respectively, and in the lower limbs of 18, 18 and three children. The mean total Burke-Fahn-Marsden score for dystonia was 45.02, and the mean Disability Impairment Scale level was 38% for dystonia and 13% for choreoathetosis. Sustained electromyography activity was observed in 20/25 children. Stretching increased electromyography activity more in children with spasticity. There were 10 re-classifications. CONCLUSION: The children had heterogenic characteristics, and 40% were reclassified after systematic movement disorder evaluation.

Epilepsy-Related Mortality in Children and Young Adults in Denmark: A Nationwide Cohort Study.

BACKGROUND AND OBJECTIVES: Mortality is increased in epilepsy, but the important issue is that a proportion of epilepsy-related death is potentially preventable by optimized therapy and therefore needs to be identified. A new systematic classification of epilepsy-related mortality has been suggested to identify these preventable deaths. We applied this classification to an analysis of premature mortality in persons with epilepsy who were <50 years of age. METHODS: The study was a population-based retrospective cohort of all Danish citizens with and without epilepsy 1 to 49 years of age during 2007 to 2009. Information on all deaths was retrieved from the Danish Cause of Death Registry, autopsy reports, death certificates, and the Danish National Patient Registry. The primary cause of death in persons with epilepsy was evaluated independently by 3 neurologist, 1 neuro-pediatrician, and 2 cardiologists. In case of uncertainty, a pathologist was consulted. All deaths were classified as either epilepsy related or not epilepsy related, and the underlying causes or modes of death were compared between persons with and without epilepsy. RESULTS: During the study period, 700 deaths were identified in persons with epilepsy, and 440 (62.9%) of these were epilepsy related, 169 (38%) directly related to seizures and 181 (41%) due to an underlying neurologic disease. Sudden unexpected death in epilepsy accounted for 80% of deaths directly related to epilepsy. Aspiration pneumonia was the cause of death in 80% of cases indirectly related to epilepsy. Compared with the background population, persons with epilepsy had a nearly 4-fold increased all-cause mortality (adjusted mortality hazard ratio 3.95 [95% confidence interval [CI] 3.64-4.27], p < 0.0001) and a higher risk of dying of various underlying causes, including alcohol-related conditions (hazard ratio 2.91 [95% CI 2.23-3.80], p < 0.0001) and suicide (hazard ratio 2.10 [95% CI 1.18-3.73], p = 0.01). DISCUSSION: The newly proposed classification for mortality in persons with epilepsy was useful in an unselected nationwide cohort. It helped in classifying unnatural causes of death as epilepsy related or not and in identifying potentially preventable deaths. The leading causes of premature mortality in persons <50 years of age were related to epilepsy and were thus potentially preventable by good seizure control.

Declining prevalence of cerebral palsy in children born at term in Denmark.

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.

Comparing Seizure-Related Death and Suicide in Younger Adults with Epilepsy.

Younger adults with epilepsy have an increased mortality. Some deaths are seizure-related, for example, sudden unexpected death in epilepsy (SUDEP), whereas others, for example, suicide, have multiple causes, including adverse effects of the treatment on mood. In this retrospective population-based study of all Danish persons with epilepsy aged 18 to 49 years during 2007 to 2009 we evaluated the risk of death from seizures and suicide. SUDEP comprised 82.7% of all seizure-related death. Younger adults with epilepsy had an 8.3-fold increased risk of death from seizure-related causes compared with suicide. This underpins the importance of effective seizure control in preventing premature death. ANN NEUROL 2021;90:983-987.

Sudden unexpected death in epilepsy in persons younger than 50 years: A retrospective nationwide cohort study in Denmark.

OBJECTIVE: Persons with epilepsy have an increased mortality including a high risk of sudden unexplained death (SUD), also referred to as sudden unexpected death in epilepsy (SUDEP). We aimed to evaluate the risk of SUDEP in comparison to other causes of death and the risk of SUD in persons with and without epilepsy. METHODS: We undertook a retrospective population-based cohort study of all Danish citizens with and without epilepsy aged 1-49 years during 2007-2009. All deaths in the population were evaluated, and all cases of SUD identified. Primary causes of death in persons with epilepsy were evaluated independently by three neurologists and one neuropediatrician, using the unified SUDEP criteria. RESULTS: The three most frequent causes of death in persons with epilepsy were cancer (2.38 per 1000 person-years), SUDEP (1.65 per 1000 person-years), and pneumonia (1.09 per 1000 person-years) compared with cancer (.17 per 1000 person-years), accident-related deaths (.14 per 1000 person-years), and cardiovascular disease (.09 per 1000 person-years) in persons without epilepsy. Considering definite, definite plus, and probable cases, the SUDEP incidence was .27 per 1000 person-years (95% confidence interval [CI] = .11-.64) in children aged 1-17 years and 1.21 per 1000 person-years (95% CI = .96-1.51) in adults aged 18-49 years. Adjusted for age and sex, persons with epilepsy younger than 50 years had a 10.8-fold (95% CI = 9.97-11.64, p < .0001) increased all-cause mortality and a 34.4-fold (95% CI = 23.57-50.28, p < .0001) increased risk of SUD compared with persons without epilepsy. SUDEP accounted for 23.3% of all SUD. SIGNIFICANCE: This nationwide study of all deaths in persons with epilepsy younger than 50 years found a lower SUDEP risk in children compared with adults, and that epilepsy was a major risk factor for SUD in the background population. This underlines the importance of addressing risk factors for SUDEP to prevent premature death.

Increase in cognitive function is seen in many single-operated pediatric patients after epilepsy surgery.

PURPOSE: The recurrent seizures of pediatric drug-resistant epilepsy (DRE) are known to impair brain development and can lead to a loss in cognitive functioning. Surgery is increasingly being used to treat children with DRE. This study investigates the pre- and postoperative cognitive function in a pediatric epilepsy surgery cohort as well as predictive determinants of change in intelligence quotient (IQ) following surgery. METHODS: A consecutive series of 91 Danish children who underwent focal resective epilepsy surgery between January 1996 and December 2016 were included. All underwent preoperative cognitive evaluation and were reevaluated at 1-year and/or 2-year follow-up. Single-operated and multi-operated patients were examined separately. RESULTS: 79 of 91 patients were single-operated. Single-operated patients received less anti-epileptic drugs (AED) and experienced a decrease in seizure frequency postoperatively, p < 0.001. IQ increased postoperatively (IQ change ± standard deviation: 3.3 ± 14.0), p < 0.05. High preoperative seizure frequency was a significant predictor for decreased IQ, p < 0.01. Multi-operated patients did not experience a reduction in AED treatment. Surgery and continued AED treatment did, however, result in significantly better seizure control, p < 0.01. IQ remained unchanged in multi-operated patients. CONCLUSION: Epilepsy surgery allowed for IQ gains in single-operated patients. Preoperative seizure frequency was a significant predictor of IQ change following surgery. Interactions between other, not included, possible predictors remain to be examined. Single-operated patients had the best cognitive outcome. The inclusion of a non-surgical control group is needed to assess the extent of the beneficial effects of surgery on cognitive ability.

Navigating being a young adult with cerebral palsy: a qualitative study.

OBJECTIVES: Young adults with cerebral palsy (CP) face potential challenges. The transition to young adulthood is characterized by significant changes in roles and responsibilities. Furthermore, young adults with chronic conditions face a transfer from pediatric care to adult healthcare. This study explores how living with CP affects young adults in general, and specifically which psychosocial, medical and healthcare needs are particularly important during this phase of life. METHODS: A qualitative study with data from individual, semi-structured, in-depth interviews with six young adults with CP (ages 21-31 years) were transcribed verbatim and analyzed. The participants were selected to provide a maximum variation in age, gender, Gross Motor Function Classification System score and educational background. A descriptive thematic analysis was used to explore patterns and identify themes. RESULTS: Three themes were identified: "Being a Young Adult", "Development in Physical Disability and New Challenges in Adulthood" and "Navigating the Healthcare System". The three themes emerged from 15 sub-themes. Our findings emphasized that young adults with CP faced psychosocial challenges in social relationships, participation in education and work settings and striving towards independence. The transition to young adulthood led to a series of new challenges that the young adults were not prepared for. Medical challenges included managing CP-related physical and cognitive symptoms and navigating adult health care services, where new physicians with insufficient knowledge regarding CP were encountered. CONCLUSION: The young adults with CP were not prepared for the challenges and changes they faced during their transition into adulthood. They felt that they had been abandoned by the healthcare system and lacked a medical home. Better transitional care is urgently needed to prepare them for the challenges in young adulthood.

Ambient Exposure to Agricultural Pesticides during Pregnancy and Risk of Cerebral Palsy: A Population-Based Study in California.

Cerebral palsy (CP) is the most common neuro-motor disability in young children. Disruptions of maternal hormone function during pregnancy have been linked to CP risk. We investigated whether prenatal exposure to pesticide compounds with endocrine-disrupting action affect CP risk. We conducted a case-control study of 3905 CP cases and 39,377 controls born between 1998 and 2010 in California to mothers who lived in proximity (within 2 km) to any agricultural pesticide application recorded in the California Pesticide Use Reporting (PUR) system. We focused on 23 pesticides considered endocrine disruptors that are frequently used, and we found that exposure to any of the 23 pesticides in the first trimester was associated with elevated CP risks in female offspring (OR = 1.19; 95% CI: 1.05-1.35) but not males (OR = 0.99; 95% CI: 0.89-1.09) compared to the unexposed offspring. Positive associations were estimated for 15 pesticides suspected to affect the estrogen and 7 pesticides suspected to affect the thyroid hormone system. Our study suggests that first trimester exposure to pesticides that are suspected endocrine disruptors are associated with CP risk in female offspring. Pesticide exposures in early pregnancy may have sex-specific influences on the neuro-motor development of the fetus by interfering with endocrine systems.

A methodological perspective on the cognitive outcome of epilepsy surgery in children and adolescents.

PURPOSE: The purpose of the study was to explore the impact of timing and test specificity of cognitive outcome measures after pediatric epilepsy surgery. METHODS: A consecutive national cohort of 114 children with medically resistant epilepsy having had resective epilepsy surgery were screened for children tested with a complete age-appropriate Wechsler Intelligence test at two or three time-points. This provided 43 children for analyses. Composite subscale scores were assessed in comparison to index and intelligence quotient (IQ) scores. RESULTS: We found a main effect of time in seizure-free children for full-scale IQ (FSIQ); F(2, 42) = 6.49 with higher T2 measures compared with T1 (MDiff = 5.46, p = .006). There was a difference in FSIQ scores between seizure-free and nonseizure-free children at T2; M = 7.31, 95% confidence interval (CI) [0.05 to 14.57], t(38) = 2.04, p = .049, favoring seizure-free children. A statistical difference between composite scale scores and index scores was found with medium to large effect. The correlation of medical treatment (anti-epileptic drug (AED)) change and score differences in FSIQ outcome was significant (p = .041), with less AED correlated with a higher FSIQ. All children with left-temporal surgery had a stable or improved verbal comprehension composite subscale score outcome at T2 regardless of seizure status. CONCLUSION: Our results correspond to some longitudinal studies with outcome measures >2 years, in contrast to short-term studies ≤2 years with a stable outcome. Our study supports the fact that the specificity of the used tests and the timing of assessments after pediatric epilepsy surgery are essential factors for the clinical validity of outcome measures. However, there are further needs of extensive longitudinal studies to provide a better understanding of life-long cognitive development and impact after childhood epilepsy surgery.

Prevalence of mental disorders in children and adolescents with cerebral palsy: Danish nationwide follow-up study.

AIM: To compare the prevalence of mental disorders (MDs) in a cohort of children and adolescents with and without cerebral palsy (CP) and to explore whether there is an association between MDs and the Gross Motor Function Classification System (GMFCS) level. METHOD: A register-linkage follow-up study of 10- to 16-year children with CP (identified in the Danish National Cerebral Palsy Registry, n = 893), and 2627 children without CP, matched by gender and age. Information on MDs was obtained from the National Patient Registry in Denmark and based on ICD-10-codes. Conditional logistic regression was performed in order to compare the prevalence of MDs. RESULTS: The prevalence of MDs was significantly higher in children and adolescents with CP (22.4%, CI 19.8-25.2%) compared with controls (6.3%, CI 5.5-7.3%). Intellectual disability was statistically significantly associated with motor function (odds ratio (OR) 4.55, CI 2.81-7.36 for GMFCS levels IV-V compared to GMFCS level I), but there were no statistically significant association between motor function and autism spectrum disorders, ADHD or affective disorders. INTERPRETATION: Our findings emphasize that follow-up of children with CP should include screening for both cognitive dysfunction and other mental disorders. The motor function does not predict the risk of other mental disorders than intellectual disability in children and adolescents with CP.

Continuing decline in the prevalence of cerebral palsy in Denmark for birth years 2008-2013.

AIM: To quantify and analyse the prevalence and clinical features of cerebral palsy (CP) in Denmark for birth years 2008-2013 and compare results with previous periods. METHOD: A nationwide register-based study covering all children with a confirmed diagnosis of CP born in Denmark. Information about CP subtype, aetiology and severity was collected from the Cerebral Palsy Follow-up Program and supplemented from medical files. Data from the Danish Medical Birth Register was included, and the results were compared to previous data from the Danish National Cerebral Palsy Register. Prevalence per 1000 live births and proportions were analysed using the Cochran-Armitage test for trend. RESULTS: The period covered 368,618 live births and 636 children with CP, making the overall prevalence for the period 1.73 per 1000 live births. This was significantly lower than the prevalence of 1.99 for the previous period 1999-2007 (p = 0.004). The decline in prevalence between the two periods was mainly due to a decrease in children with bilateral spastic and dyskinetic CP born after 37 gestational weeks. The decline in prevalence was accompanied by a smaller proportion of children with associated impairment. CONCLUSION: We found a decrease in prevalence and severity in CP among Danish children. The decline was most pronounced in children born after 37 gestational weeks with severe subtypes of CP. National guidelines that recommend induction of labour before the completion of week 42 and therapeutic hypothermia for term neonates with hypoxic-ischaemic encephalopathy, may have contributed to the decline.