Abstracts

Rationale:
Epilepsies disproportionately affect young children. Early childhood epilepsies are frequently resistant to therapy and associated with cognitive and behavioural comorbidity. It is hoped that precision therapy approaches, targeted at addressing underlying aetiology, will play a major role in closing the treatment gap. Epidemiological data utilising modern diagnostic techniques including next generation sequencing genetics and neuroimaging should inform diagnostic strategies and therapeutic trials.
Method:
A three-year multi-centre prospective cohort study, involving all children in the Scottish universal health care system presenting with epilepsies between May 2014 and May 2017. Capture-recapture methodology was used utilising two independent sources. Socio-demographic and clinical details were obtained at presentation, and again 24 months after presentation.  Epilepsy syndrome was classified 24 months after presentation. Children were extensively investigated for aetiology, including whole genome sequencing for unresolved cases. A multivariate logistic regression model was used to determine associations between clinical features, aetiology, and outcome.
Results:
Three hundred and ninety children were recruited. The incidence of epilepsy < 3 years was 240 per 100,000 live births (95% confidence intervals 216-265), or 1 per 417 live births. Mortality was 3% by 24 months (13 deaths). There was a socio-economic gradient to the incidence of epilepsies. Incidence in the most deprived quintile of the population was 338 per 100,000 (95% CI 284-403) and in the least deprived quintile was 203 per 100,000 (95% CI 156-261). Etiology was determined in 54% of children, and epilepsy syndrome classified in 41%. Overall, 133 patients (34%) had a monogenic epilepsy, and 72 (18%) had a structural epilepsy. The overall incidence of monogenic epilepsies was 178 per 100,000 (95% CI 66-93), or 1 per 952 live births. Sixty-seven (66%) of all single gene diagnoses involved one of the nine most frequently implicated genes. We provide incidence estimates for the more common epilepsy syndromes of childhood. The incidence of early infantile developmental and epileptic encephalopathy (DEE) was 10.0 per 100,000 (95% CI 5.8-16.0), Dravet syndrome was 6.5 per 100,000 (95% CI 3.2-10.0), and infantile spasms syndrome was 30.7 per 100,000 (95% CI 22.9-40.2). By 24 months after presentation, 36% of children had drug-resistant epilepsy (DRE), and 49% had global developmental delay (GDD). Identification of etiology strongly correlated with both DRE and GDD. Etiology was determined in 83% with DRE, and 76% with GDD.
Conclusion:
Early childhood epilepsies are at least 30% more common than previously reported. Etiology can be identified in a high proportion of cases, encouraging development of precision therapies.  More deprived communities will require greater epilepsy-related resources.
Funding:
:This research was supported by grants from Dravet Syndrome UK, Epilepsy Research UK, Glasgow Children’s Hospital Charity, and UCB Pharma.