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1.
Neurology ; 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35577577

RESUMO

BACKGROUND AND OBJECTIVES: Women with epilepsy treated with antiseizure medication (ASM) have increased risk of pregnancy complications including preterm birth, fetal growth restriction and preeclampsia. We aimed to investigate whether folic acid supplementation is associated with these pregnancy complications in women with epilepsy using ASM. METHODS: Singleton pregnancies in the prospective Norwegian Mother and Child Cohort Study (MoBa) (1999-2008) were included. Information on maternal epilepsy, ASM, folic acid supplementation, and pregnancy outcomes was obtained from MoBa questionnaires and the Norwegian Medical Birth Registry. The main exposure, periconceptional folic acid supplementation, was defined as intake between 4 weeks before pregnancy and 12 weeks into pregnancy, retrospectively collected by recall of the mothers in week 17-19. The primary outcomes were preterm birth (gestational age <37 weeks at birth), small for gestational age (SGA), and preeclampsia. RESULTS: The study included 100,105 pregnancies; 99,431 without maternal epilepsy, 316 with maternal epilepsy and ASM exposure in pregnancy, and 358 with untreated maternal epilepsy. Among ASM-treated women with epilepsy, the risk of preterm birth was higher in those who did not use periconceptional folic acid (n=64) compared to those who did (n=245, the reference) (adjusted odds ratio (aOR) 3.3, 95% confidence interval (CI) 1.2-9.2), while the risk of preterm birth among the reference was similar to the risk among women without epilepsy using folic acid periconceptionally (aOR 0.9, 95% CI 0.5-1.6). ASM-treated women with epilepsy starting folic acid after the first trimester had a higher risk compared to women without epilepsy with similar timing of folic acid (aOR 2.6, 95% CI 1.1-6.5), and even higher if not using folic acid (aOR 9.4, 95% CI 2.6-34.8). Folic acid was not associated with risk of preterm birth among women with epilepsy without ASM or among women without epilepsy. Folic acid was not associated with risk of preeclampsia or SGA among women with epilepsy. DISCUSSION: In women with epilepsy using ASM, periconceptional folic acid was associated with a lower risk of preterm birth. This finding supports the recommendation that ASM-treated women with epilepsy of childbearing potential should use folic acid supplementation on a regular basis. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for women with epilepsy using ASM, periconceptional folic acid supplementation decreases the risk of preterm birth.

2.
Clin Epidemiol ; 14: 445-452, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35418783

RESUMO

Objective: The Danish National Patient Registry (DNPR) is a valuable resource for medical and epidemiological Research. However, not all research articles fully described procedures they used to identify events. In this study, we compared two approaches in identifying persons with a disease diagnosis using neonatal jaundice and epilepsy as examples. Methods: A cohort of singletons born alive between the 1st January 1997 and the 30th November 2016 in Denmark was used for this purpose. Diagnostic information for a hospital contact in the registry included a primary diagnosis, secondary diagnoses, referral diagnoses, and additional information to a diagnosis (associated diagnoses), if any. Approach 1 identified patients of interest by considering all diagnostic information with exclusion of referral diagnoses only. Approach 2 identified patients of interest by additionally excluding diagnoses from a hospital contact that were coded with Z00 - Z99 of ICD-10 (for health service on examination and reproduction, etc.) as the main reason of the hospital contact. We presented the proportion of people with a diagnosis of neonatal jaundice and epilepsy by the two approaches and explored the potential explanations for the difference. Results: For the example of neonatal jaundice, the study population included N=1,186,683 persons. The proportion of children with a diagnosis of neonatal jaundice was 5.5% (n=66,736) by approach 1 and 3.9% (n=45,928) by approach 2. For the example of epilepsy, the study population included N=1,183,273 persons. The proportion of children with a diagnosis of epilepsy were 1.2% (n=14,604) by approach 1 and 0.9% (n=10,441) by approach 2. Discussion: This study demonstrated that the two approaches identified different proportion of persons with a diagnosis of neonatal jaundice and epilepsy. We advocated researchers report complete procedures of identifying patients for making research findings reproducible and comparable.

3.
Eur J Neurol ; 2022 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-35340074

RESUMO

BACKGROUND AND PURPOSE: This position paper makes recommendations following an audit of care provided to people presenting with a seizure to emergency departments (EDs) in Europe. METHODS: Participating countries were asked to include five hospitals agreeing to identify 50 consecutive seizure patients presenting to their ED between 1 August 2016 and 31 August 2017. Anonymous data were collected to a web database. Where quoted, percentages are mean site values and ranges are the 10th-90th centile. RESULTS: Data were collected on 2204 ED visits (47 sites, up to six per country, across 15 countries): 1270 (58%) known epilepsy, 299 (14%) previous blackouts but no epilepsy diagnosis, 634 (29%) with a first seizure. Wide variability was identified for most variables. Of those with known epilepsy, 41.2% (range 26.2%-59.6%) attended the ED in the previous 12 months, but only 64.7% (range 37.2%-79.8%) had seen an epilepsy specialist in the previous 12 months. 67.7% (range 34.0%-100%) were admitted, 53.1% to a neurology ward (range 0.0%-88.9%). Only 37.5% first seizure patients (range 0.0%-71.4%) were given advice about driving. CONCLUSIONS AND RECOMMENDATIONS: It is recommended that in Europe guidance is agreed on the management and onward referral of those presenting to the ED with a seizure; a referral process is created that can be easily implemented; it is ensured that the seizure services receive referrals and see the patients within a short time period; and a simple system is developed and implemented to allow continuous monitoring of key indices of epilepsy care.

4.
Acta Neurol Scand ; 145(6): 721-729, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35243615

RESUMO

OBJECTIVES: Traumatic brain injury (TBI) and perinatal adversities such as low gestational age at birth, low birth weight, low Apgar, and being born small for gestational age are well-established risk factors for epilepsy. We examined whether perinatal adversities modified the risk of epilepsy after TBI in a nationwide cohort study of Danish singletons born from 1982 to 2011. MATERIALS AND METHODS: We categorized perinatal adversities as a composite measure of preterm delivery, low birth weight, low Apgar score, or being born small for gestational age. Cox regression and competing risk regression were used to estimate the risk of epilepsy after TBI according to such perinatal adversities. The study included 1,715,095 singletons (51.1% males). The mean age at end of follow-up was 19.3 years (Interquartile range [IQR] = 12.1-26.3). During follow-up, 85,636 persons (58.2% males) sustained a TBI and 18,064 developed epilepsy (50.7% males), of whom 1329 persons had a preceding TBI. RESULTS: The hazard ratio (HR) of epilepsy in persons with perinatal adversities was 1.19 (95% confidence interval [CI] 1.15-1.24), compared to persons without. The HR of epilepsy in persons with TBI was 2.31 (95% CI 2.18-2.45) compared to persons without TBI, but this risk was not modified by perinatal adversities (p = 0.2460). CONCLUSIONS: Perinatal adversities and TBI both increased the risk of epilepsy, but the risk of epilepsy after TBI was not modified by these perinatal adversities.


Assuntos
Lesões Encefálicas Traumáticas , Epilepsia , Adulto , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/epidemiologia , Estudos de Coortes , Dinamarca/epidemiologia , Epilepsia/epidemiologia , Epilepsia/etiologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Gravidez , Adulto Jovem
5.
Brain ; 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35234848

RESUMO

Mortality rates are 2-3 times higher in people with epilepsy than in the general population. This study aimed to quantify how this increased mortality translates into reduced life expectancy and to identify the underlying causes of deaths, thereby offering suggestions for how to reduce mortality associated with epilepsy. In this population-based cohort study, we included all individuals aged 0-94 years who were living in Denmark between 2000 and 2015. Using the nationwide registers, we identified persons diagnosed with epilepsy and estimated the excess of life years lost due to 13 overall and 9 specific causes of death. Among 6,022,160 persons, we identified 129,598 persons with epilepsy (52.6% males), with a mean age of epilepsy onset of 36.5 years (standard deviation = 26.3 years). During the 16 years of follow-up, 851,087 individuals died, and of these 36,923 had been diagnosed with epilepsy. The average reduction in life expectancy in persons with epilepsy was 11.84 years in males (95% confidence interval: 11.66-12.00) and 10.91 years in females (95% confidence interval: 10.70-11.11) compared to the general population. Life expectancy was reduced irrespective of epilepsy etiology (symptomatic approximately 14 years; idiopathic approximately 8-10 years), and in particular in persons with epilepsy and psychiatric comorbidity (approximately 13-16 years). Excess mortality was evident across all causes of death including cardiovascular disorders, accidents, and suicide. People with epilepsy experience a substantial reduction in lifespan that can only partly be explained by underlying conditions. Prevention of epilepsy-related deaths should focus on the consequences of psychiatric comorbidity and on modifiable risk factors associated with preventable causes of death such as accidents, neurological and cardiovascular disorders.

6.
Am J Hum Genet ; 109(3): 417-432, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-35139346

RESUMO

Genome-wide association studies (GWASs) have revolutionized human genetics, allowing researchers to identify thousands of disease-related genes and possible drug targets. However, case-control status does not account for the fact that not all controls may have lived through their period of risk for the disorder of interest. This can be quantified by examining the age-of-onset distribution and the age of the controls or the age of onset for cases. The age-of-onset distribution may also depend on information such as sex and birth year. In addition, family history is not routinely included in the assessment of control status. Here, we present LT-FH++, an extension of the liability threshold model conditioned on family history (LT-FH), which jointly accounts for age of onset and sex as well as family history. Using simulations, we show that, when family history and the age-of-onset distribution are available, the proposed approach yields statistically significant power gains over LT-FH and large power gains over genome-wide association study by proxy (GWAX). We applied our method to four psychiatric disorders available in the iPSYCH data and to mortality in the UK Biobank and found 20 genome-wide significant associations with LT-FH++, compared to ten for LT-FH and eight for a standard case-control GWAS. As more genetic data with linked electronic health records become available to researchers, we expect methods that account for additional health information, such as LT-FH++, to become even more beneficial.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Idade de Início , Estudos de Casos e Controles , Estudo de Associação Genômica Ampla/métodos , Humanos , Anamnese
7.
Ann Neurol ; 91(4): 455-465, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35148430

RESUMO

OBJECTIVE: We examined how maternal epilepsy and use of antiseizure medications in pregnancy was associated with offspring mortality. METHODS: This population-based cohort study included all live- and stillborn singletons in Denmark between 1981 and 2016. We used nation-wide registers to retrieve information on pregnancy characteristics, epilepsy diagnoses, use of antiseizure medications, and mortality. Adjusted mortality rate ratios (MRR) were estimated using log-linear Poisson regression. RESULTS: The cohort consisted of 1,862,474 children. In total, 12,026 live-born children died during follow-up, of whom 170 (1.4%) were offspring of mothers with epilepsy. Overall mortality was increased in offspring of mothers with epilepsy compared to offspring of mothers without epilepsy (MRR = 1.46, 95% CI: 1.23-1.71), driven by an excess mortality only in the first year of life. Mortality was increased for natural deaths (MRR = 1.50, 95% CI: 1.25-1.78) but not from unnatural deaths (MRR = 1.38, 95% CI: 0.84-2.14), and only in offspring of women with epilepsy who used antiseizure medications during pregnancy (MRR = 1.51, 95% CI: 1.00-2.17), but not in offspring of women with epilepsy who did not use antiseizure medications while pregnant (MRR = 0.97, 95% CI: 0.69-1.31). When analyses were restricted to children born from 2000 and onwards, the excess mortality that was observed in the first year of life among children of mothers with epilepsy, was no longer evident. INTERPRETATION: During the 1981 to 1999 epoch, offspring of women with epilepsy were at increased risk of dying in the first year of life. However, this risk did not extend to children born after 2000. Future retrospective studies of the effects of maternal epilepsy on the health of the offspring should take this difference into account. ANN NEUROL 2022;91:455-465.


Assuntos
Epilepsia , Criança , Estudos de Coortes , Epilepsia/tratamento farmacológico , Feminino , Humanos , Modelos Lineares , Mães , Gravidez , Estudos Retrospectivos
9.
Brain ; 145(2): 555-568, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35022648

RESUMO

Febrile seizures represent the most common type of pathological brain activity in young children and are influenced by genetic, environmental and developmental factors. In a minority of cases, febrile seizures precede later development of epilepsy. We conducted a genome-wide association study of febrile seizures in 7635 cases and 83 966 controls identifying and replicating seven new loci, all with P < 5 × 10-10. Variants at two loci were functionally related to altered expression of the fever response genes PTGER3 and IL10, and four other loci harboured genes (BSN, ERC2, GABRG2, HERC1) influencing neuronal excitability by regulating neurotransmitter release and binding, vesicular transport or membrane trafficking at the synapse. Four previously reported loci (SCN1A, SCN2A, ANO3 and 12q21.33) were all confirmed. Collectively, the seven novel and four previously reported loci explained 2.8% of the variance in liability to febrile seizures, and the single nucleotide polymorphism heritability based on all common autosomal single nucleotide polymorphisms was 10.8%. GABRG2, SCN1A and SCN2A are well-established epilepsy genes and, overall, we found positive genetic correlations with epilepsies (rg = 0.39, P = 1.68 × 10-4). Further, we found that higher polygenic risk scores for febrile seizures were associated with epilepsy and with history of hospital admission for febrile seizures. Finally, we found that polygenic risk of febrile seizures was lower in febrile seizure patients with neuropsychiatric disease compared to febrile seizure patients in a general population sample. In conclusion, this largest genetic investigation of febrile seizures to date implicates central fever response genes as well as genes affecting neuronal excitability, including several known epilepsy genes. Further functional and genetic studies based on these findings will provide important insights into the complex pathophysiological processes of seizures with and without fever.


Assuntos
Epilepsia , Convulsões Febris , Anoctaminas/genética , Criança , Pré-Escolar , Epilepsia/genética , Febre/complicações , Febre/genética , Estudo de Associação Genômica Ampla , Humanos , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Convulsões Febris/genética
10.
Neuroepidemiology ; 56(2): 138-146, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35051933

RESUMO

INTRODUCTION: Onset of febrile seizures varies with calendar season. However, it has not previously been assessed, how season of birth interacts with age and peak risk of febrile seizures, and whether season of birth correlates with the cumulative risk of febrile seizures at 5 years of age (i.e., when children are no longer of risk of febrile seizures). METHODS: We identified all singleton children born in Denmark between 1977 and 2011 who were alive at 3 months of age (N = 2,103,232). We used the Danish Civil Registration System to identify age and sex of the children and the Danish National Patient Register to identify children hospitalized with febrile seizures from 3 months to 5 years of age. Follow-up ended on December 31, 2016, when all children had reached 5 years of age. RESULTS: The relative risk of admission with a first febrile seizure varied with calendar month; in February (a winter month in Denmark), the risk was more than doubled (hazard ratio: 2.10 [95% confidence interval [CI]: 2.03-2.18]) compared with August (a summer month in Denmark). The age-specific incidence of a first febrile seizure by birth month identified the highest peak incidence of a first febrile seizure among children born in November (reaching a peak incidence of 350 first admissions with a febrile seizure per 100,000 person months at age 16 months) as compared to children born in July (reaching a peak incidence of 200 first admissions with a febrile seizure per 100,000 person months at age 16 months). However, the cumulative incidence of any admission with febrile seizures before 5 years was not correlated with season of birth (3.69% [95% CI: 3.64-3.74%] for winter births, 3.57% [95% CI: 3.52-3.62%] for spring births, 3.55% [95% CI: 3.50-3.59%] for summer births, and 3.64% [95% CI: 3.59-3.69%] for fall births). DISCUSSION/CONCLUSION: The study found a significant seasonal variation in onset of the first febrile seizure and in the age-specific peak incidence of febrile seizures. However, there was no correlation between season of birth and cumulative incidence of febrile seizures at 5 years of age suggesting that children who are predisposed to febrile seizures will eventually go on to experience a febrile seizure regardless of season of birth.


Assuntos
Convulsões Febris , Criança , Estudos de Coortes , Dinamarca/epidemiologia , Humanos , Incidência , Lactente , Estações do Ano , Convulsões Febris/epidemiologia , Convulsões Febris/etiologia
11.
Ugeskr Laeger ; 184(3)2022 01 17.
Artigo em Dinamarquês | MEDLINE | ID: mdl-35060475

RESUMO

Critically ill patients are at high risk of non-convulsive status epilepticus (NCSE). As clinical signs of NCSE are subtle and unspecific, EEG is necessary to make the diagnosis. This is a review of the terminology for EEG reporting and the criteria for NCSE in critically ill patients. We discuss the newly proposed ictal-interictal continuum, and how caution is needed when assessing EEG criteria in order to avoid both over- and undertreatment. Finally, we discuss how specific EEG findings, in combination with clinical information, can help infer treatment decision and need for continuous EEG monitoring.


Assuntos
Estado Terminal , Estado Epiléptico , Eletroencefalografia , Humanos , Monitorização Fisiológica , Estado Epiléptico/diagnóstico , Estado Epiléptico/tratamento farmacológico
12.
Epileptic Disord ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34859792

RESUMO

OBJECTIVE: To characterize in detail the electroclinical features of typical absence seizures and elucidate whether EEG or semiology features, alone or in combination, can predict long-term therapeutic outcome. METHODS: We analysed video-EEG recordings from 213 typical absence seizures from 61 patients with idiopathic generalized epilepsy. We extracted semiological features, in addition to hallmark manifestations (motor/behavioural arrest, non-responsiveness), their location, timing and frequency. We evaluated the duration and frequency of generalized spike-wave discharges and the presence of polyspikes. We used a supervised machine-learning approach (random forest) to search for classifier features for long-term therapeutic outcome (>one year). RESULTS: Besides the hallmark manifestations, additional semiological features were identified in 87% of patients (75% of seizures). The most common additional semiological features were automatisms and eye blinking (observed in 45% and 41.5% of seizures, respectively). Automatisms were associated with longer seizure duration, and oral automatisms occurred earlier compared to limb automatisms (4.03 vs. 6.19 seconds; p=0.005). The mean duration of the ictal spike-wave discharges was nine seconds, and the median frequency was 3 Hz. Polyspikes occurred in 46 seizures (21.6%), in 19 patients (31%). Median follow-up was five years, and 73% of the patients were seizure-free at the end of the follow-up. None of the semiological features, alone or in combination, were predictors of therapeutic outcome. The only significant classifier was the presence of polyspikes, predicting a non-seizure-free outcome with an accuracy of 73% (95% CI: 70-77%), positive predictive value of 92% (95% CI: 84-98%) and negative predictive value of 60% (95% CI: 39-81%). SIGNIFICANCE: Semiological features, in addition to behavioural arrest and non-responsiveness, are common in typical absence seizures, but they do not predict long-term therapeutic outcome. The presence of polyspikes has a high positive predictive value for unfavourable therapeutic outcome, and their presence should therefore be included when reporting EEGs in patients with typical absence seizures.

13.
JAMA ; 326(17): 1725-1735, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34726709

RESUMO

Importance: Concerns exist about long-term neurodevelopmental consequences of prenatal exposure to antidepressants. Objective: To evaluate whether maternal prescription fill for antidepressants in pregnancy was associated with performance in standardized tests among Danish schoolchildren. Design, Setting, and Participants: Population-based retrospective cohort study of children born in Denmark between January 1, 1997, and December 31, 2009, attending public primary and lower secondary school. The children included had completed a language or mathematics test as part of the Danish National Test Program between January 1, 2010, and December 31, 2018. The age range of the eligible schoolchildren was 7 to 17 years. Exposures: Maternal prescription fill for antidepressants during pregnancy, obtained from the Danish Prescription Register. Main Outcomes and Measures: The difference in standardized scores between children with and without maternal prescription fill for antidepressants in mathematics and language tests (scale, 1-100; higher scores indicate better test results) was estimated using linear regression models, adjusted for relevant confounders. Ten sensitivity analyses were performed, including a sibling-controlled analysis. Results: Among the 575 369 children included (51.1% males), 10 198 (1.8%) were born to mothers filling an antidepressant prescription during pregnancy. The mean (SD) age of children at the time of testing spanned from 8.9 (0.4) years in grade 2 to 14.9 (0.4) years in grade 8. Maternal prescription fill for antidepressants was significantly associated with a poorer performance in mathematics (mean test scores for the group exposed to maternal antidepressant fill: 52.1 [95% CI, 51.7-52.6] and for the group not exposed to maternal antidepressant fill: 57.4 [95% CI, 57.3-57.4]; adjusted difference, -2.2 [95% CI, -2.7 to -1.6]), but not in language (mean test scores for the exposed group: 53.4 [95% CI, 53.1-53.7] and for the not exposed group: 56.6 [95% CI, 56.5-56.6]; adjusted difference, -0.1 [95% CI, -0.6 to 0.3]). In the sibling-controlled analysis, the adjusted difference in mathematics (mean scores for the exposed group: 53.5 [95% CI, 52.7-54.3] and for the not exposed group: 59.0 [95% CI, 58.9-59.1]) was -2.8 (95% CI, -4.5 to -1.2) and in language (mean test scores for the exposed group: 53.9 [95% CI, 53.2-54.6] and for the not exposed group: 56.6 [95% CI, 56.5-56.7]) was -0.3 (95% CI, -1.9 to 1.2). Conclusions and Relevance: In this study of public schoolchildren in Denmark, children whose mothers had filled prescriptions for antidepressants during pregnancy, compared with children whose mothers did not fill prescriptions for antidepressants during pregnancy, had a 2-point lower standardized test score in mathematics, a difference that was statistically significant, but had no significant difference in language test scores. The magnitude of the difference in the mathematics test score was small and of uncertain clinical importance, and the findings must be weighed against the benefits of treating maternal depression during pregnancy.


Assuntos
Desempenho Acadêmico , Antidepressivos/efeitos adversos , Depressão/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal , Adolescente , Adulto , Antidepressivos/uso terapêutico , Criança , Dinamarca , Feminino , Humanos , Idioma , Masculino , Matemática , Gravidez , Estudos Retrospectivos , Adulto Jovem
14.
Epilepsia ; 62(12): 2981-2993, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34585373

RESUMO

OBJECTIVE: Prenatal exposure to the antiseizure medication (ASM) valproate is associated with an increased risk of congenital malformations, but warnings against the use of valproate in pregnancy were not issued until 2009. The objective was to study how early administrative health registers could have identified the teratogenic risk associated with valproate. METHODS: This was a population-based cohort study of individual-linked data from Danish health care and socioeconomic registers including children born in Denmark between January 1, 1997 and December 31, 2014. Information on ASM use, including valproate, in pregnancy was obtained from the Danish National Prescription Registry. Children identified with major congenital malformations from the Danish National Patient Register and the Danish Register of Causes of Death were included. Using logistic regression models, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for major congenital malformations during the first year of life in children with and without prenatal exposure to ASMs adjusted for potential confounders. RESULTS: Among the 895 507 children (males, 51.3%), 31 790 (3.6%) were diagnosed with a major congenital malformation in the first year of life. In the analyses including children born in 1997, the risk of major congenital malformations among children prenatally exposed to valproate compared with children not exposed to ASMs was increased by a fully adjusted OR (aOR) of 3.95 (95% CI = 1.65-9.47). With the addition of data from the following years, the teratogenic effect of valproate was further substantiated, as the precision of the estimate improved (1997-2014: aOR = 2.44, 95% CI = 1.80-3.30). SIGNIFICANCE: Using Danish health care data, we were able to identify a teratogenic risk associated with prenatal valproate exposure in children born in 1997, which is much earlier than prospective clinical cohorts. Health registry data represent an important tool for early identification of risk associated with drugs in pregnancy.


Assuntos
Complicações na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Anticonvulsivantes/efeitos adversos , Criança , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Gravidez , Complicações na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos Prospectivos , Sistema de Registros , Ácido Valproico/efeitos adversos
15.
Epilepsia ; 62(12): 2899-2908, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34558066

RESUMO

OBJECTIVE: Imaging activated glutamate N-methyl-D-aspartate receptor ion channels (NMDAR-ICs) using positron emission tomography (PET) has proved challenging due to low brain uptake, poor affinity and selectivity, and high metabolism and dissociation rates of candidate radioligands. The radioligand [18 F]GE-179 is a known use-dependent marker of NMDAR-ICs. We studied whether interictal [18 F]GE-179 PET would detect foci of abnormal NMDAR-IC activation in patients with refractory focal epilepsy. METHODS: Ten patients with refractory focal epilepsy and 18 healthy controls had structural magnetic resonance imaging (MRI) followed by a 90-min dynamic [18 F]GE-179 PET scan with simultaneous electroencephalography (EEG). PET and EEG findings were compared with MRI and previous EEGs. Standard uptake value (SUV) images of [18 F]GE-179 were generated and global gray matter uptake was measured for each individual. To localize focal increases in uptake of [18 F]GE-179, the individual SUV images were interrogated with statistical parametric mapping in comparison to a normal database. Additionally, individual healthy control SUV images were compared with the rest of the control database to determine their prevalence of increased focal [18 F]GE-179 uptake. RESULTS: Interictal [18 F]GE-179 PET detected clusters of significantly increased binding in eight of 10 patients with focal epilepsy but none of the controls. The number of clusters of raised [18 F]GE-179 uptake in the patients with epilepsy exceeded the focal abnormalities revealed by the simultaneously recorded EEG. Patients with extensive clusters of raised [18 F]GE-179 uptake showed the most abnormal EEGs. SIGNIFICANCE: Detection of multiple foci of abnormal NMDAR-IC activation in 80% of our patients with refractory focal epilepsy using interictal [18 F]GE-179 PET could reflect enhanced neuronal excitability due to chronic seizure activity. This indicates that chronic epileptic activity is associated with abnormal NMDAR ion channel activation beyond the initial irritative zones. [18 F]GE-179 PET could be a candidate marker for identifying pathological brain areas in patients with treatment-resistant focal epilepsy.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Epilepsia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/metabolismo , Eletroencefalografia , Epilepsias Parciais/diagnóstico por imagem , Epilepsias Parciais/metabolismo , Epilepsia/metabolismo , Fluordesoxiglucose F18/metabolismo , Humanos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons/métodos , Receptores de N-Metil-D-Aspartato/metabolismo
16.
Epilepsia ; 62(11): 2651-2666, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34472627

RESUMO

OBJECTIVE: This study aimed to determine the prevalence of epilepsy in four European countries (Austria, Denmark, Ireland, and Romania) employing a standard methodology. The study was conducted under the auspices of ESBACE (European Study on the Burden and Care of Epilepsy). METHODS: All hospitals and general practitioners serving a region of at least 50 000 persons in each country were asked to identify patients living in the region who had a diagnosis of epilepsy or experienced a single unprovoked seizure. Medical records were accessed, where available, to complete a standardized case report form. Data were sought on seizure frequency, seizure type, investigations, etiology, comorbidities, and use of antiseizure medication. Cases were validated in each country, and the degree of certainty was graded as definite, probable, or suspect cases. RESULTS: From a total population of 237 757 in the four countries, 1988 (.8%) patients were identified as potential cases of epilepsy. Due to legal and ethical issues in the individual countries, medical records were available for only 1208 patients, and among these, 113 had insufficient clinical information. The remaining 1095 cases were classified as either definite (n = 706, 64.5%), probable (n = 191, 17.4%), suspect (n = 153, 14.0%), or not epilepsy (n = 45, 4.1%). SIGNIFICANCE: Although a precise prevalence estimate could not be generated from these data, the study found a high validity of epilepsy classification among evaluated cases (95.9%). More generally, this study highlights the significant challenges facing epidemiological research methodologies that are reliant on patient consent and retrospective chart review, largely due to the introduction of data protection legislation during the study period. Documentation of the epilepsy diagnosis was, in some cases, relatively low, indicating a need for improved guidelines for assessment, follow-up, and documentation. This study highlights the need to address the concerns and requirements of recruitment sites to engage in epidemiological research.


Assuntos
Epilepsia , Epilepsia/diagnóstico , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Europa (Continente)/epidemiologia , Humanos , Prevalência , Estudos Retrospectivos , Convulsões/prevenção & controle
17.
Neurology ; 97(5): e464-e475, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34031196

RESUMO

OBJECTIVE: Knowledge regarding psychiatric disorders in children and adolescents with psychogenic nonepileptic seizures (PNES) is limited. This study outlines the spectrum and risk of psychiatric disorders in childhood-onset PNES. METHODS: We performed a nationwide matched cohort study of children and adolescents with PNES 5 to 17 years of age at the time of diagnosis between January 1, 1996, and December 31, 2014. Two matched comparison groups were included: children and adolescents with epilepsy (ES) and children and adolescents without PNES or epilepsy, called healthy controls (HC). Outcomes were prevalent psychiatric disorders before index (i.e., date of diagnosis or corresponding date for HC) and incident psychiatric disorders 2 years after index. Relative risks (RRs) were calculated and adjusted for potential confounders. RESULTS: We included 384 children and adolescents with validated PNES, 1,152 with ES, and 1,920 HC. Among the cases of PNES, 153 (39.8%) had prevalent psychiatric disorders and 150 (39.1%) had incident psychiatric disorders. Compared to the ES and HC groups, children and adolescents with PNES had elevated risks of both prevalent psychiatric disorders (adjusted RRPNES/ES 1.87, 95% confidence interval [CI] 1.59-2.21, adjusted RRPNES/HC 5.54, 95% CI 4.50-6.81) and incident psychiatric disorders (adjusted RRPNES/ES 2.33, 95% CI 1.92-2.83, adjusted RRPNES/HC 8.37, 95% CI 6.31-11.11). A wide spectrum of specific psychiatric disorders displayed elevated RRs. CONCLUSIONS: Children and adolescents with PNES are at higher risk of a wide range of psychiatric disorders compared to children and adolescents with ES and HC. A careful psychiatric evaluation is warranted to optimize and individualize treatment.


Assuntos
Transtornos Dissociativos/complicações , Transtornos Dissociativos/psicologia , Transtornos Mentais/complicações , Transtornos Mentais/psicologia , Convulsões/complicações , Convulsões/psicologia , Adolescente , Sintomas Afetivos/complicações , Sintomas Afetivos/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Dinamarca/epidemiologia , Eletroencefalografia , Feminino , Humanos , Incidência , Classificação Internacional de Doenças , Masculino , Transtornos Mentais/epidemiologia , Pais , Prevalência , Sistema de Registros , Medição de Risco
18.
Acta Neurol Scand ; 144(1): 51-57, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33822360

RESUMO

OBJECTIVE: Febrile seizure is a common childhood disorder that affects 2-5% of all children, and is associated with later development of epilepsy and psychiatric disorders. This study determines how the incidence of febrile seizures correlates with birth characteristics, age, sex and brain development. METHODS: This is a cohort study of all children born Denmark between 1977 and 2011 who were alive at 3 months of age (N = 2,103,232). The Danish National Patient Register was used to identify children with febrile seizures up to 5 years of age. Follow-up ended on 31 December 2016 when all cohort members had potentially reached 5 years of age. RESULTS: In total, 75,593 (3.59%, 95% CI: 3.57-3.62%) were diagnosed with febrile seizures. Incidence peaked at 16.7 months of age (median: 16.7 months, interquartile range: 12.5-24.0). The 5-year cumulative incidence of febrile seizures increased with decreasing birth weight (<1500 g; 5.42% (95% CI: 4.98-5.88% vs. 3,000-4,000 g; 3.53% (95% CI: 3.50-3.56%)) and with decreasing gestational age at birth (31-32 weeks; 5.90% (95% CI: 5.40-6.44%) vs. 39-40 weeks; 3.56% (95% CI: 3.53-3.60)). Lower gestational age at birth was associated with higher age at onset of a first febrile seizure; an association that essentially disappeared when correcting for age from conception. CONCLUSIONS: The risk of febrile seizures increased with decreasing birth weight and gestational age at birth. The association between low gestational age at birth and age at first febrile seizure suggests that onset of febrile seizures is associated with the stage of brain development.


Assuntos
Peso ao Nascer/fisiologia , Desenvolvimento Infantil/fisiologia , Idade Gestacional , Convulsões Febris/diagnóstico , Convulsões Febris/epidemiologia , Pré-Escolar , Estudos de Coortes , Dinamarca/epidemiologia , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Sistema de Registros , Fatores de Risco , Convulsões Febris/fisiopatologia , Fatores Sexuais
19.
Epilepsia ; 62(5): 1158-1169, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33734434

RESUMO

OBJECTIVE: To investigate social outcome and psychiatric comorbidity of patients with idiopathic/genetic generalized epilepsies (IGEs) and its subtypes (epilepsy with generalized tonic-clonic seizures alone [EGTCS], juvenile absence epilepsy [JAE], and juvenile myoclonic epilepsy [JME]). METHODS: A cohort of 402 adult patients with IGE from the Danish island Funen was matched with 4020 randomly selected geography-, age-, and sex-matched controls via the Danish Civil Registration System. Based on register data, we compared social status measured by cohabitant status, educational attainment, income, affiliation to labor market, and psychiatric comorbidity. RESULTS: As compared to controls, patients with IGE had similar cohabitant status but fewer children (no children: 59.0% vs 50.9%), and lower educational level (primary school only: 46.0% vs 37.3%), employment rate (outside of workforce: 56.7% vs 46.5%), and income (low income: 32.6% vs 24.9%) (P < 0.001 for all comparisons). Having IGE was associated with higher a proportion of psychiatric comorbidity (IGE, 22.6%; controls, 13.0%) (P < 0.001). Seizure-free patients did not differ from controls; patients with persistent seizures had lower incomes and employment rates. In the IGE subgroup analyses, JME was associated with worse social status in all parameters studied (eg, 65.9% of JME patients were outside the workforce vs 44.5% of matched controls; P < 0.001), whereas no adverse social status was identified in patients with EGTCS and JAE. SIGNIFICANCE: Patients with IGE in general and JME in particular have poorer social status and more psychiatric comorbidity than matched population controls without epilepsy. Poor seizure control was associated with social status and may contribute to negative socioeconomic consequences associated with IGE.


Assuntos
Epilepsia Generalizada/psicologia , Transtornos Mentais/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Epilepsia Generalizada/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distância Psicológica , Fatores Sociais , Adulto Jovem
20.
Brain ; 144(3): 875-884, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33439977

RESUMO

Traumatic brain injury is associated with increased risk of epilepsy, but the importance of repeated traumatic brain injuries has not yet been established. We performed a nationwide population-based cohort study of 2 476 905 individuals born in Denmark between 1977 and 2016. We estimated hazard ratios (HRs) and the cumulative incidence of epilepsy following traumatic brain injury using Cox and competing risk regression, respectively. To estimate the cumulative incidence of epilepsy in the population without traumatic brain injury, we matched 10 controls for each subject with traumatic brain injury on year of birth, sex, and date of brain insult in the index person. In the cohort, traumatic brain injury was sustained by 167 051 subjects (71 162 females and 95 889 males), and 37 200 individuals developed epilepsy (17 905 females and 19 295 males). Compared with subjects without traumatic brain injury, the relative risk of epilepsy increased after a first traumatic brain injury [HR 2.04, 95% confidence interval (CI) 1.96-2.13] and even more after a second traumatic brain injury (HR 4.45, 95% CI 4.09-4.84). The risk increased with the severity of the first and the second traumatic brain injury, most notably after severe traumatic brain injuries. Females were more likely than males to develop epilepsy after mild traumatic brain injury (HR 2.13, 95% CI 2.00-2.28 versus HR 1.77, 95% CI 1.66-1.88; P < 0.0001); in contrast, males were more likely than females to develop epilepsy after severe traumatic brain injury (HR 5.00, 95% CI 4.31-5.80 versus 3.21, 95% CI 2.56-4.03; P = 0.0012). The risk remained increased for decades after the traumatic brain injury. This knowledge may inform efforts to prevent the development of post-traumatic epilepsy.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Epilepsia/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Fatores de Risco , Adulto Jovem
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