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  • 1
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    Accidental deaths in young people with epilepsy and psychiatric comorbidity—A Danish nationwide cohort study
    Wiley ; 2020
    In:  Epilepsia Vol. 61, No. 3 ( 2020-03), p. 479-488
    Details
    In: Epilepsia, Wiley, Vol. 61, No. 3 ( 2020-03), p. 479-488
    Abstract: The objective of this study was to investigate the accident‐related mortality among people younger than 55 years of age with epilepsy compared with the general population and to study how psychiatric comorbidity influences this risk. Methods This is a population‐based cohort study of individuals born in Denmark between 1960 and 2015 (n = 3, 665 616). Persons diagnosed with epilepsy and psychiatric disorders were identified in the Danish National Patient Register and the Danish Central Psychiatric Central Register. We estimated the hazard ratio (HR) with 95% confidence intervals (CIs) of accidental death in people with epilepsy compared with persons without epilepsy. Results We identified 61 330 persons (1.7%) diagnosed with epilepsy. Median age at end of follow‐up was 27.8 years. In people with epilepsy, 5253 died during follow‐up, 480 (9%) of whom died from accidents. Among people without epilepsy, 52 588 died during follow‐up, of whom 1280 (2.4%) died from accidents. People with epilepsy had a 3.7‐fold (95% CI 3.4‐4.1) increased risk of accidental death compared with persons without epilepsy. When we adjusted for psychiatric disorders, the risk remained significantly elevated in people with epilepsy compared to people without epilepsy (adjusted HR [aHR] 2.44, 95% CI 2.22‐2.69). When stratifying the analyses on epilepsy and psychiatric disorders, people with epilepsy and psychiatric disorders had an aHR of 4.95 (95% CI 3.82‐6.41) when compared with persons without epilepsy and psychiatric disorders. Significance The risk of accidental death was increased in people with epilepsy and was particularly high among people with epilepsy with psychiatric comorbidity. The findings highlight the need for awareness and prevention strategies in people with epilepsy, especially in people with comorbid psychiatric disorders.
    Type of Medium: Online Resource
    ISSN: 0013-9580 , 1528-1167
    URL: Issue
    URL: Article
    DOI: 10.1111/epi.v61.3
    DOI: 10.1111/epi.16453
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2002194-X
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  • 2
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    Traumatic brain injury, stroke, and epilepsy: A mediation study in a Danish nationwide cohort
    Wiley ; 2023
    In:  Epilepsia Vol. 64, No. 3 ( 2023-03), p. 718-727
    Details
    In: Epilepsia, Wiley, Vol. 64, No. 3 ( 2023-03), p. 718-727
    Abstract: Traumatic brain injury (TBI) and stroke are well‐known causes of acquired epilepsy. TBI is also a risk factor for stroke, and injury‐induced stroke may indirectly convey a proportion of the epilepsy risk following TBI. We studied the extent to which the effect of TBI on epilepsy operated through intermediary stroke. Methods We analyzed a nationwide, matched, register‐based cohort of adults 40 years of age whose first TBI at Danish hospitals was recorded between 2004 and 2016. A matched reference population was sampled for comparison. During follow‐up, we recorded all acute strokes. Cox proportional hazard models and the difference method were used to estimate the total and controlled direct effect hazard ratios (HRs) of TBI on epilepsy and the indirect effect HRs of TBI on epilepsy operating through stroke, and to calculate the proportion eliminated. Analyses were stratified by severity of, age at, and time since TBI. Results We followed 57 900 persons with TBI (48.6% males) from median age 61 years (interquartile range = 51–75), and 561 977 age‐ and sex‐matched references. The total effect of TBI on epilepsy was higher for persons aged 40–59 years (HR = 5.15, 95% confidence interval [CI] = 4.65–5.72) than for persons aged 60 years (HR = 4.55, 95% CI = 4.19–4.95). In contrast, the indirect effect of TBI mediated by stroke was lower for persons aged 40–59 years (HR = 1.02, 95% CI = 1.02–1.03) than for persons aged 60 years (HR = 1.05, 95% CI = 1.04–1.06). We estimated 2.3% and 5.6% of the risk of epilepsy after TBI to operate through stroke for these age groups, respectively. Significance Less than 6% of the risk of epilepsy following TBI operated through intermediary stroke. However, this mechanism seems to play an increasing role with age and for late onset epilepsies. This warrants further investigation.
    Type of Medium: Online Resource
    ISSN: 0013-9580 , 1528-1167
    URL: Article
    DOI: 10.1111/epi.17497
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 3
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    Parental age and risk of epilepsy: A nationwide register‐based study
    Wiley ; 2018
    In:  Epilepsia Vol. 59, No. 7 ( 2018-07), p. 1334-1343
    Details
    In: Epilepsia, Wiley, Vol. 59, No. 7 ( 2018-07), p. 1334-1343
    Abstract: This study aims to examine the association between maternal age, paternal age, and parental age difference at the time of birth and the risk of epilepsy in the offspring. Methods We carried out a prospective population‐based register study of all singletons born in Denmark between 1981 and 2012. Cox regression was used to estimate hazard ratios ( HR s) of epilepsy and their corresponding 95% confidence intervals ( CI s), adjusted for relevant confounders. Results We followed 1 587 897 individuals for a total of ~25 million person‐years and identified 21 797 persons with epilepsy during the study period. An excess risk of epilepsy was found in individuals born to mothers younger than 20 years ( HR = 1.17, 95% CI = 1.07‐1.29) and born to parental couples where paternal age exceeded maternal age by at least 5 years. The risk of epilepsy increased with increasing parental age gap and was highest when the father was ≥15 years older than the mother (adjusted HR = 1.28, 95% CI = 1.16‐1.41). In contrast to maternal age, we found that paternal age did not independently contribute to offspring epilepsy risk, once we accounted for the parental age difference ( P  = .1418). The observed associations with maternal age and parental age gap were invariant to epilepsy subtypes, but were modified by age of epilepsy onset, with the effect being most pronounced in the first 10 years of the child's life. Significance Maternal age and parental age gap, but not paternal age, were associated with the offspring's risk of epilepsy. Our results do not support the hypothesis that de novo mutations associated with advanced paternal age increase the risk of epilepsy in the offspring.
    Type of Medium: Online Resource
    ISSN: 0013-9580 , 1528-1167
    URL: Issue
    URL: Article
    DOI: 10.1111/epi.2018.59.issue-7
    DOI: 10.1111/epi.14453
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2018
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  • 4
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    Birth characteristics and risk of febrile seizures
    Hindawi Limited ; 2021
    In:  Acta Neurologica Scandinavica Vol. 144, No. 1 ( 2021-07), p. 51-57
    Details
    In: Acta Neurologica Scandinavica, Hindawi Limited, Vol. 144, No. 1 ( 2021-07), p. 51-57
    Type of Medium: Online Resource
    ISSN: 0001-6314 , 1600-0404
    URL: Issue
    URL: Article
    DOI: 10.1111/ane.v144.1
    DOI: 10.1111/ane.13420
    RVK:
    XA 10000
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2001898-8
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  • 5
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    Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes
    Oxford University Press (OUP) ; 2022
    In:  Brain Vol. 145, No. 2 ( 2022-04-18), p. 555-568
    Details
    In: Brain, Oxford University Press (OUP), Vol. 145, No. 2 ( 2022-04-18), p. 555-568
    Abstract: 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 & lt; 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.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awab260
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 6
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    Antiepileptic Drugs and Suicide: Role of Prior Suicidal Behavior and Parental Psychiatric Disorder
    Wiley ; 2019
    In:  Annals of Neurology Vol. 86, No. 6 ( 2019-12), p. 951-961
    Details
    In: Annals of Neurology, Wiley, Vol. 86, No. 6 ( 2019-12), p. 951-961
    Abstract: To examine whether prior suicidal behavior and familial predisposition to psychiatric disorders modify the association between antiepileptic drug use and completed suicide. Methods Using the Danish National Prescription Register, we identified all incident users of antiepileptic drugs aged 15 years or older in Denmark between July 1997 and December 2015. We carried out a nested case–control study and defined exposure to antiepileptic drugs at the index date (ie, time of suicide). Conditional logistic regressions were used to estimate mortality rate ratios (MRRs) of suicide in current versus previous users of antiepileptic drugs. We also analyzed suicide risk associated with the 9 most commonly used antiepileptic drugs. Results We identified 1,759 individuals completing suicide. Current versus previous use of any antiepileptic drug was associated with an increased risk of suicide (MRR = 1.26, 95% confidence interval [CI] = 1.13–1.40). This excess risk was observed in individuals with a history of suicidal behavior (MRR = 1.28, 95% CI = 1.07–1.54) and in those without (MRR = 1.26, 95% CI = 1.11–1.43), and in individuals with a familial predisposition to psychiatric disorders (MRR = 1.48, 95% CI = 1.18–1.87) and in those without (MRR = 1.21, 95% CI = 1.07–1.35). Interpretation Use of antiepileptic drugs was associated with an increased risk of suicide. The findings do not support that the risk of suicide following treatment with antiepileptic drugs identified in randomized trials is explained by prior suicidality or familial predisposition to psychiatric disorders. The additional risk of suicide associated with use of antiepileptic drugs was generally low and should be balanced against benefits of treatment. ANN NEUROL 2019;86:951–961
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    URL: Article
    DOI: 10.1002/ana.v86.6
    DOI: 10.1002/ana.25623
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2037912-2
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  • 7
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    Epilepsy risk in offspring of affected parents; a cohort study of the “maternal effect” in epilepsy
    Wiley ; 2021
    In:  Annals of Clinical and Translational Neurology Vol. 8, No. 1 ( 2021-01), p. 153-162
    Details
    In: Annals of Clinical and Translational Neurology, Wiley, Vol. 8, No. 1 ( 2021-01), p. 153-162
    Abstract: To assess whether the risk of epilepsy is higher in offspring of mothers with epilepsy than in offspring of fathers with epilepsy. Methods In a prospective population‐based register study, we considered all singletons born in Denmark between 1981 and 2016 ( N  = 1,754,742). From the Danish National Patient Register since 1977, we identified epilepsy diagnoses in all study participants and their family members. Cox regression models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CI), adjusted for relevant confounders. Results We included 1,754,742 individuals contributing 〉  30 million person‐years of follow‐up. The incidence rate of epilepsy in offspring of unaffected parents was 78.8 (95% CI: 77.8–79.8) per 100,000 person‐years, while the corresponding rate in offspring with an affected father was 172 per 100,000 person‐years (95% CI: 156–187) and in offspring with an affected mother was 260 per 100,000 person‐years (95% CI: 243–277). Having an affected mother was associated with a 1.45‐fold (95% CI: 1.30–1.63) higher risk of epilepsy in the offspring, compared to having an affected father. This maternal effect was found both in male (HR = 1.39, 95% CI: 1.19–1.62) and female offspring (HR = 1.53, 95% CI: 1.30–1.80), and across various ages at onset in the offspring. The maternal effect was also found in familial epilepsies (i.e. where the affected parent had an affected sibling; HR = 1.50, 95% CI: 1.04−2.16). Interpretation We found a clear maternal effect on offspring risk of epilepsy in this nationwide cohort study.
    Type of Medium: Online Resource
    ISSN: 2328-9503 , 2328-9503
    URL: Issue
    URL: Article
    DOI: 10.1002/acn3.v8.1
    DOI: 10.1002/acn3.51258
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2740696-9
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  • 8
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    Repeated traumatic brain injury and risk of epilepsy: a Danish nationwide cohort study
    Oxford University Press (OUP) ; 2021
    In:  Brain Vol. 144, No. 3 ( 2021-04-12), p. 875-884
    Details
    In: Brain, Oxford University Press (OUP), Vol. 144, No. 3 ( 2021-04-12), p. 875-884
    Abstract: 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  & lt; 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.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awaa448
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 9
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    73. ACCOUNTING FOR FAMILY HISTORY AND AGE OF ONSET IMPROVES POWER IN GENOME-WIDE ASSOCIATION STUDIES
    Elsevier BV ; 2021
    In:  European Neuropsychopharmacology Vol. 51 ( 2021-10), p. e80-
    Details
    In: European Neuropsychopharmacology, Elsevier BV, Vol. 51 ( 2021-10), p. e80-
    Type of Medium: Online Resource
    ISSN: 0924-977X
    URL: Article
    DOI: 10.1016/j.euroneuro.2021.07.161
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2019305-1
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  • 10
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    Seasonal Variation and Risk of Febrile Seizures: A Danish Nationwide Cohort Study
    S. Karger AG ; 2022
    In:  Neuroepidemiology Vol. 56, No. 2 ( 2022), p. 138-146
    Details
    In: Neuroepidemiology, S. Karger AG, Vol. 56, No. 2 ( 2022), p. 138-146
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 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). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We identified all singleton children born in Denmark between 1977 and 2011 who were alive at 3 months of age ( 〈 i 〉 N 〈 /i 〉 = 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. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 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). 〈 b 〉 〈 i 〉 Discussion/Conclusion: 〈 /i 〉 〈 /b 〉 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.
    Type of Medium: Online Resource
    ISSN: 0251-5350 , 1423-0208
    URL: Article
    DOI: 10.1159/000522065
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2022
    detail.hit.zdb_id: 1483032-2
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