Screening of attention and executive functions in pediatric patients at a tertiary epilepsy center.

OBJECTIVE: Executive dysfunction is prevalent in children with epilepsy, and associated with poor psychosocial outcome. Sensitive and time effective tools are needed, which capture executive dysfunction across a wide range of impairment. The present study evaluates the applicability of EpiTrack Junior® (EpiTrackJr) as a screening tool at a tertiary epilepsy center, and explore how EpiTrackJr in combination with a subjective measure of everyday attention and executive functions (EFs) may provide clinically important information. METHODS: Retrospective study including 235 pediatric patients admitted to the Norwegian National Centre for Epilepsy. EpiTrackJr and Behavioral Rating Inventory of Executive Functioning (BRIEF) were used to assess attention and EFs. RESULTS: 27,7% obtained a score categorized as "average/unimpaired", 23% as "mildly impaired", and 47.7% as "significantly impaired" on EpiTrackJr. The distribution of age-corrected EpiTrackJr scores was satisfactory. Performance was related to numbers of anti-seizure medication (ASM load), comorbidity and IQ. We found a significant, but weak correlation between EpiTrackJr performance and the BRIEF Metacognitive Index (r = -0.236, n = 108, p=.014), but no significant correlation with the Behavioral Regulation Index (r = -0.178, n = 108, p=.065). SIGNIFICANCE: Our results indicate that EpiTrackJr is applicable as a screening tool for attention and EFs in pediatric patients at a tertiary epilepsy center. Impaired test performance was associated with greater ASM load, comorbidity and lower IQ. Performance based measures and behavior ratings likely capture different aspects of EFs. In combination, the two provide important and nonredundant information about the child's EFs in different settings.

Changes in the use of antiseizure medications in children and adolescents in Norway, 2009-2018.

BACKGROUND: The use of antiseizure medications (ASMs) in the pediatric population is poorly studied. The purpose of this study was to investigate changes in the use of ASMs in children and adolescents compared to adults, and to elucidate safety considerations of certain drugs. METHOD: In this population-based pharmacoepidemiological study we used the Norwegian Prescription Database (NorPD), 2009-2018. The use of ASMs is presented as 1-year prevalence per 1000: number of ASM users in a year * 1000 / number of inhabitants that year. Variables included predetermined 5-year age groups, gender, ASMs, diagnosis-specific reimbursement codes, user, and population numbers. Selected ASMs used for specific indications or subgroups included ethosuximide, sulthiame, rufinamide, stiripentol, and clobazam. Gender differences in the use of valproate was examined due to safety considerations in girls/women. RESULTS: The total number of ASM users (all indications) for the age groups 0-19 and 20-59 years was 5807 and 47,481 respectively in 2009, and 5906 and 61,447 respectively in 2018. The 1-year prevalence for children/adolescents (0-19 years) using ASMs in epilepsy remained stable from 2008 to 2018, 4.3-4.2/1000 inhabitants, as compared to 8.2-7.6/1000 in adults (20-59 years). Valproate, lamotrigine, and levetiracetam were the three most used ASMs in epilepsy in children/adolescents, similar to adults. The selected ASMs were mainly used in children/ adolescents, accounting for 0.74/1000 in 2018 versus 0.17/1000 in adults. A significant increase was seen for sulthiame (8-fold), ethosuximide (4-fold), clobazam (3-fold), and stiripentol (2-fold). The use of ASMs in non-epilepsy indications was limited and stable (17% in 2018); mainly lamotrigine in psychiatry in adolescents (15-19 years). This finding was in contrast to extensive non-epilepsy use in adults (71% in 2018). CONCLUSION: Changes in the use of ASMs in children/adolescents differ as compared to adults, most notably extensive and increasing use of selected ASMs and limited non-epilepsy. This is an important part of pharmacovigilance and patient safety evaluations.

Childhood seizures after prenatal exposure to maternal influenza infection: a population-based cohort study from Norway, Australia and Canada.

OBJECTIVE: To assess whether clinical and/or laboratory-confirmed diagnosis of maternal influenza during pregnancy increases the risk of seizures in early childhood. DESIGN: Analysis of prospectively collected registry data for children born between 2009 and 2013 in three high-income countries. We used Cox regression to estimate country-level adjusted HRs (aHRs); fixed-effects meta-analyses were used to pool adjusted estimates. SETTING: Population-based. PARTICIPANTS: 1 360 629 children born between 1 January 2009 and 31 December 2013 in Norway, Australia (New South Wales) and Canada (Ontario). EXPOSURE: Clinical and/or laboratory-confirmed diagnosis of maternal influenza infection during pregnancy. MAIN OUTCOME MEASURES: We extracted data on recorded seizure diagnosis in secondary/specialist healthcare between birth and up to 7 years of age; additional analyses were performed for the specific seizure outcomes 'epilepsy' and 'febrile seizures'. RESULTS: Among 1 360 629 children in the study population, 14 280 (1.0%) were exposed to maternal influenza in utero. Exposed children were at increased risk of seizures (aHR 1.17, 95% CI 1.07 to 1.28), and also febrile seizures (aHR 1.20, 95% CI 1.07 to 1.34). There was no strong evidence of an increased risk of epilepsy (aHR 1.07, 95% CI 0.81 to 1.41). Risk estimates for seizures were higher after influenza infection during the second and third trimester than for first trimester. CONCLUSIONS: In this large international study, prenatal exposure to influenza infection was associated with increased risk of childhood seizures.

Comorbidities in cerebral palsy: a patient registry study.

AIM: To describe the total burden of disease in individuals with cerebral palsy (CP) in Norway. METHOD: A comprehensive set of disorder categories were extracted from the Norwegian Patient Registry using International Statistical Classification of Diseases, 10th Revision diagnosis codes for individuals born between 1996 and 2010 who received specialist healthcare between 2008 and 2017 (0-21y). Individuals with CP were identified through a validation study in cooperation with the Cerebral Palsy Registry of Norway. Risk differences (proportions of individuals recorded with each disorder) were used to compare individuals with CP with the general population without CP. RESULTS: The study included 966 760 individuals. Among these, 2302 (0.24%) had CP (1330 males, 972 females). Of the individuals with CP, 95.0% were recorded with one or more comorbidity, and the risks of medical, neurological, and mental/behavioural disorders were higher compared with the risks in the general population. The most common neurological and mental/behavioural disorders were cocausal, i.e. attributed to the same injury to the developing brain that caused CP, while medical disorders were most often complications of CP or coincidentally co-occurring with CP. INTERPRETATION: Individuals with CP have a considerably higher burden of medical, neurological, and mental/behavioural disorders compared with the general population, including disorders that are not directly caused by, or complications to, the brain injury. WHAT THIS PAPER ADDS: Nearly all individuals with cerebral palsy (CP) had one or more comorbidity. Fifty-two per cent had at least one comorbidity attributed to the same cause as CP, complications of CP, and coincidentally co-occurring with CP. Risks of medical, neurological, and mental/behavioural disorders were considerably higher than in the general population.

Epilepsy in Children After Pandemic Influenza Vaccination.

OBJECTIVES: To determine if pandemic influenza vaccination was associated with an increased risk of epilepsy in children. METHODS: Information from Norwegian registries from 2006 through 2014 on all children <18 years living in Norway on October 1, 2009 was used in Cox regression models to estimate hazard ratios for incident epilepsy after vaccination. A self-controlled case series analysis was used to estimate incidence rate ratios in defined risk periods after pandemic vaccination. RESULTS: In Norway, the main period of the influenza A subtype H1N1 pandemic was from October 2009 to December 2009. On October 1, 2009, 1 154 113 children <18 years of age were registered as residents in Norway. Of these, 572 875 (50.7%) were vaccinated against pandemic influenza. From October 2009 through 2014 there were 3628 new cases of epilepsy (incidence rate 6.09 per 10 000 person-years). The risk of epilepsy was not increased after vaccination: hazard ratio: 1.07; 95% confidence interval: 0.94-1.23. Results from the self-controlled case series analysis supported the finding of no association between vaccination and subsequent epilepsy. CONCLUSIONS: Pandemic influenza vaccination was not associated with increased risk of epilepsy. Concerns about pandemic vaccination causing epilepsy in children seem to be unwarranted.

Discontinuation of antiepileptic drugs in seizure-free patients - when and how? / Seponering av antiepileptika ved anfallsfrihet ­ når og hvordan?

In seizure-free patients with epilepsy, the question of whether, and if so when, it is acceptable to withdraw treatment may be difficult to answer. A thorough risk-benefit assessment should be undertaken with the patient and next of kin, during which the consequences of a relapse must be weighed against the disadvantages of continued administration of the drug. As a main rule, adult patients should have been seizure-free for at least two years before discontinuation is considered. In children with epilepsy with a known good prognosis, discontinuation may be considered even earlier.

Comorbidities treated in primary care in children with chronic fatigue syndrome / myalgic encephalomyelitis: A nationwide registry linkage study from Norway.

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a complex condition. Causal factors are not established, although underlying psychological or immunological susceptibility has been proposed. We studied primary care diagnoses for children with CFS/ME, with children with another hospital diagnosis (type 1 diabetes mellitus [T1DM]) and the general child population as comparison groups. METHODS: All Norwegian children born 1992-2012 constituted the study sample. Children with CFS/ME (n = 1670) or T1DM (n = 4937) were identified in the Norwegian Patient Register (NPR) (2008-2014). Children without either diagnosis constituted the general child population comparison group (n = 1337508). We obtained information on primary care diagnoses from the Norwegian Directorate of Health. For each primary care diagnosis, the proportion and 99 % confidence interval (CI) within the three groups was calculated, adjusted for sex and age by direct standardization. RESULTS: Children with CFS/ME were more often registered with a primary care diagnosis of weakness/general tiredness (89.9 % [99 % CI 88.0 to 91.8 %]) than children in either comparison group (T1DM: 14.5 % [99 % CI: 13.1 to 16.0 %], general child population: 11.1 % [99 % CI: 11.0 to 11.2 %]). Also, depressive disorder and anxiety disorder were more common in the CFS/ME group, as were migraine, muscle pain, and infections. In the 2 year period prior to the diagnoses, infectious mononucleosis was registered for 11.1 % (99 % CI 9.1 to 13.1 %) of children with CFS/ME and for 0.5 % (99 % CI (0.2 to 0.8 %) of children with T1DM. Of children with CFS/ME, 74.6 % (1292/1670) were registered with a prior primary care diagnosis of weakness / general tiredness. The time span from the first primary care diagnosis of weakness / general tiredness to the specialist health care diagnosis of CFS/ME was 1 year or longer for 47.8 %. CONCLUSIONS: This large nationwide registry linkage study confirms that the clinical picture in CFS/ME is complex. Children with CFS/ME were frequently diagnosed with infections, supporting the hypothesis that infections may be involved in the causal pathway. The long time span often observed from the first diagnosis of weakness / general tiredness to the diagnosis of CFS/ME might indicate that the treatment of these patients is sometimes not optimal.

'North Sea' progressive myoclonus epilepsy: phenotype of subjects with GOSR2 mutation.

We previously identified a homozygous mutation in the Golgi SNAP receptor complex 2 gene (GOSR2) in six patients with progressive myoclonus epilepsy. To define the syndrome better we analysed the clinical and electrophysiological phenotype in 12 patients with GOSR2 mutations, including six new unrelated subjects. Clinical presentation was remarkably similar with early onset ataxia (average 2 years of age), followed by myoclonic seizures at the average age of 6.5 years. Patients developed multiple seizure types, including generalized tonic clonic seizures, absence seizures and drop attacks. All patients developed scoliosis by adolescence, making this an important diagnostic clue. Additional skeletal deformities were present, including pes cavus in four patients and syndactyly in two patients. All patients had elevated serum creatine kinase levels (median 734 IU) in the context of normal muscle biopsies. Electroencephalography revealed pronounced generalized spike and wave discharges with a posterior predominance and photosensitivity in all patients, with focal EEG features seen in seven patients. The disease course showed a relentless decline; patients uniformly became wheelchair bound (mean age 13 years) and four had died during their third or early fourth decade. All 12 cases had the same variant (c.430G>T, G144W) and haplotype analyses confirmed a founder effect. The cases all came from countries bounding the North Sea, extending to the coastal region of Northern Norway. 'North Sea' progressive myoclonus epilepsy has a homogeneous clinical presentation and relentless disease course allowing ready identification from the other progressive myoclonus epilepsies.