Risk of epilepsy in neonates with seizures

Abstract

Seizures occur more frequently during the neonatal period than in any other time of life. Neonates with seizures have an increased risk of mortality and neurodevelopmental sequalae such as epilepsy, cognitive and motor disability, sleep, and behavioural dysfunction. The clinical conundrum of accurate diagnosis of neonatal seizures and optimal interventional packages persists.¹

There are wide variations (6%–56%) in estimates of neurodevelopmental sequelae in survivors of neonatal seizures due to varying methods of identification of seizures, size of population, case series versus population-based studies, socioeconomic status, geographical location, duration of follow-up, and type of assessments undertaken. Accurate diagnosis of seizures in the neonate is the first essential step to assess efficacy of therapies and to prognosticate with confidence.

In this useful, large, well conducted register-based cohort study of all children born in Denmark between 1997 and 2018,² Tinggaard et al. confirm the increased risk of epilepsy among survivors of neonatal seizures, with a cumulative risk of about 20%. The majority of those who had postneonatal epilepsy had onset in the first year of life, and those with structural abnormalities in the brain had a higher risk, confirming previous reports. The reported persistence of the increased risk of epilepsy into adolescence and young adulthood, will be useful for counselling. An interesting and surprising finding from the study is the increased risk of febrile seizures in survivors of neonatal seizures who did not have postneonatal epilepsy.

Neonates with seizures may have electrographic-only seizures, electroclinical-only seizures, or both.³ It is well known that underestimation and overdiagnosis of seizures may occur in neonates.⁴ Correct identification of neonates with seizures and estimation of seizure burden is an essential first step for meaningful interventional and follow-up studies. The modification for neonates of the International League Against Epilepsy classification of seizures and the epilepsies⁵ clearly recognize conventional video electroencephalogram (EEG) as the criterion standard for diagnosis and monitoring of seizures in the neonate. However, conventional EEG monitoring is not available in most parts of the world. The authors acknowledge that the identification of many neonates with seizures in their cohort may have been based on clinical features (most probably had amplitude-integrated EEG or conventional EEG confirmation), and thus a limitation of the study.²

Most neonatal seizures are provoked or symptomatic in nature. However, a small number are of genetic origin and an early aetiological diagnosis may guide personalized therapy and influence aetiological classifications and outcomes.¹

It is important for the global health community to harness resources to facilitate good clinical care with early accurate diagnosis of seizures in the neonate, identification of aetiology, development of tailored treatment packages, evaluation of therapies, assessment of epilepsy, and other neurodevelopmental and health outcomes over an extended period of follow-up, as well as precise prognostication. This study by Tinggaard et al. is a good addition to the literature in this area.