Early childhood epilepsies: epidemiology, classification, aetiology, and socio-economic determinants.

Autor:	Symonds JD; Paediatric Neurosciences Research Group, Royal Hospital for Children, Glasgow G51 4TF, UK.; Institute of Health and Wellbeing, University of Glasgow, Glasgow G12 8QQ, UK., Elliott KS; Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK., Shetty J; Department of Paediatric Neurosciences, Royal Hospital for Sick Children, Sciennes Road, Edinburgh EH9 1LF, UK., Armstrong M; UCB Pharma, Braine l'Alleud, Belgium., Brunklaus A; Paediatric Neurosciences Research Group, Royal Hospital for Children, Glasgow G51 4TF, UK.; Institute of Health and Wellbeing, University of Glasgow, Glasgow G12 8QQ, UK., Cutcutache I; UCB Pharma, Slough, UK., Diver LA; West of Scotland Regional Genetics Service, Queen Elizabeth University Hospitals, Glasgow G51 4TF, UK., Dorris L; Paediatric Neurosciences Research Group, Royal Hospital for Children, Glasgow G51 4TF, UK.; Institute of Health and Wellbeing, University of Glasgow, Glasgow G12 8QQ, UK., Gardiner S; West of Scotland Regional Genetics Service, Queen Elizabeth University Hospitals, Glasgow G51 4TF, UK., Jollands A; Paediatric Neurology, Tayside Children's Hospital, Dundee DD1 9SY, UK., Joss S; West of Scotland Regional Genetics Service, Queen Elizabeth University Hospitals, Glasgow G51 4TF, UK., Kirkpatrick M; Paediatric Neurology, Tayside Children's Hospital, Dundee DD1 9SY, UK.; School of Medicine, University of Dundee DD1 9SY, UK., McLellan A; Department of Paediatric Neurosciences, Royal Hospital for Sick Children, Sciennes Road, Edinburgh EH9 1LF, UK., MacLeod S; Paediatric Neurosciences Research Group, Royal Hospital for Children, Glasgow G51 4TF, UK., O'Regan M; Paediatric Neurosciences Research Group, Royal Hospital for Children, Glasgow G51 4TF, UK.; Paediatric Neurology, Crumlin Children's Hospital, Cooley Rd, Crumlin, Dublin D12 N512, Ireland., Page M; UCB Pharma, Braine l'Alleud, Belgium., Pilley E; Department of Paediatric Neurosciences, Royal Hospital for Sick Children, Sciennes Road, Edinburgh EH9 1LF, UK.; Paediatric Neurology, Tayside Children's Hospital, Dundee DD1 9SY, UK., Pilz DT; West of Scotland Regional Genetics Service, Queen Elizabeth University Hospitals, Glasgow G51 4TF, UK., Stephen E; Paediatric Neurology, Royal Aberdeen Children's Hospital, Aberdeen AB25 2ZG, UK., Stewart K; West of Scotland Regional Genetics Service, Queen Elizabeth University Hospitals, Glasgow G51 4TF, UK., Ashrafian H; Division of Cardiovascular Medicine, John Radcliffe Hospital, Oxford, UK.; Department of Experimental Therapeutics, Radcliffe Department of Medicine, John Radcliffe Hospital, Oxford, UK., Knight JC; Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK., Zuberi SM; Paediatric Neurosciences Research Group, Royal Hospital for Children, Glasgow G51 4TF, UK.; Institute of Health and Wellbeing, University of Glasgow, Glasgow G12 8QQ, UK.
Jazyk:	angličtina
Zdroj:	Brain : a journal of neurology [Brain] 2021 Oct 22; Vol. 144 (9), pp. 2879-2891.
DOI:	10.1093/brain/awab162
Abstrakt:	Epilepsies of early childhood are frequently resistant to therapy and often associated with cognitive and behavioural comorbidity. Aetiology focused precision medicine, notably gene-based therapies, may prevent seizures and comorbidities. Epidemiological data utilizing modern diagnostic techniques including whole genome sequencing and neuroimaging can inform diagnostic strategies and therapeutic trials. We present a 3-year, multicentre prospective cohort study, involving all children under 3 years of age in Scotland presenting with epilepsies. We used two independent sources for case identification: clinical reporting and EEG record review. Capture-recapture methodology was then used to improve the accuracy of incidence estimates. Socio-demographic and clinical details were obtained at presentation, and 24 months later. Children were extensively investigated for aetiology. Whole genome sequencing was offered for all patients with drug-resistant epilepsy for whom no aetiology could yet be identified. Multivariate logistic regression modelling was used to determine associations between clinical features, aetiology, and outcome. Three hundred and ninety children were recruited over 3 years. The adjusted incidence of epilepsies presenting in the first 3 years of life was 239 per 100 000 live births [95% confidence interval (CI) 216-263]. There was a socio-economic gradient to incidence, with a significantly higher incidence in the most deprived quintile (301 per 100 000 live births, 95% CI 251-357) compared with the least deprived quintile (182 per 100 000 live births, 95% CI 139-233), χ2 odds ratio = 1.7 (95% CI 1.3-2.2). The relationship between deprivation and incidence was only observed in the group without identified aetiology, suggesting that populations living in higher deprivation areas have greater multifactorial risk for epilepsy. Aetiology was determined in 54% of children, and epilepsy syndrome was classified in 54%. Thirty-one per cent had an identified genetic cause for their epilepsy. We present novel data on the aetiological spectrum of the most commonly presenting epilepsies of early childhood. Twenty-four months after presentation, 36% of children had drug-resistant epilepsy (DRE), and 49% had global developmental delay (GDD). Identification of an aetiology was the strongest determinant of both DRE and GDD. Aetiology was determined in 82% of those with DRE, and 75% of those with GDD. In young children with epilepsy, genetic testing should be prioritized as it has the highest yield of any investigation and is most likely to inform precision therapy and prognosis. Epilepsies in early childhood are 30% more common than previously reported. Epilepsies of undetermined aetiology present more frequently in deprived communities. This likely reflects increased multifactorial risk within these populations. (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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