The severe epilepsy syndromes of infancy: A population-based study
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Updated: Nov 20, 2025
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Published on: September 20, 2024
Katherine B Howell1,2,3, Jeremy L Freeman1,3, Mark T Mackay2,3
1Department of Neurology, Royal Children's Hospital, Melbourne, Vic, Australia.
Insights
Severe infantile epilepsies are often diagnosed as specific syndromes, guiding early treatment and prognosis. West syndrome and West syndrome-like epilepsy are most common, with significant developmental delays and mortality in affected infants.
Area of Science:
- Pediatric Neurology
- Epileptology
- Developmental Neuroscience
Background:
- Severe epilepsies in infancy present diagnostic and therapeutic challenges.
- Accurate classification of epilepsy syndromes is crucial for understanding disease trajectory.
Purpose of the Study:
- To investigate the incidence, etiologies, and outcomes of severe epilepsy syndromes in infants.
- To assess the utility of syndrome diagnosis in early infantile epilepsies.
Main Methods:
- Population-based cohort study in Victoria, Australia, of infants with epilepsy onset before 18 months.
- Diagnosis of International League Against Epilepsy epilepsy syndromes by two epileptologists using clinical data, videos, and EEGs.
- Determination of incidence, etiologies, and 2-year outcomes.
Main Results:
- 64% of infants met criteria for epilepsy syndromes, with 14% having variants.
- West syndrome and West syndrome-like epilepsy were most common (32.7/100,000 live births/year).
- Structural etiologies were frequent in some syndromes, while genetic disorders predominated in others; 16% mortality and 42% severe-profound developmental delay by age 2.
Conclusions:
- A significant majority of severe infantile epilepsies can be classified into syndromes or variant syndromes.
- Syndrome diagnosis at presentation is clinically valuable for guiding etiological investigations, treatment, and prognosis, even with advanced diagnostics.
- Early identification of epilepsy syndromes aids in predicting outcomes and tailoring interventions for infants.
Objective:
To study the epilepsy syndromes among the severe epilepsies of infancy and assess their incidence, etiologies, and outcomes.
Methods:
A population-based cohort study was undertaken of severe epilepsies with onset before age 18 months in Victoria, Australia. Two epileptologists reviewed clinical features, seizure videos, and electroencephalograms to diagnose International League Against Epilepsy epilepsy syndromes. Incidence, etiologies, and outcomes at age 2 years were determined.
Results:
Seventy-three of 114 (64%) infants fulfilled diagnostic criteria for epilepsy syndromes at presentation, and 16 (14%) had "variants" of epilepsy syndromes in which there was one missing or different feature, or where all classical features had not yet emerged. West syndrome (WS) and "WS-like" epilepsy (infantile spasms without hypsarrhythmia or modified hypsarrhythmia) were the most common syndromes, with a combined incidence of 32.7/100 000 live births/year. The incidence of epilepsy of infancy with migrating focal seizures (EIMFS) was 4.5/100 000 and of early infantile epileptic encephalopathy (EIEE) was 3.6/100 000. Structural etiologies were common in "WS-like" epilepsy (100%), unifocal epilepsy (83%), and WS (39%), whereas single gene disorders predominated in EIMFS, EIEE, and Dravet syndrome. Eighteen (16%) infants died before age 2 years. Development was delayed or borderline in 85 of 96 (89%) survivors, being severe-profound in 40 of 96 (42%). All infants with EIEE or EIMFS had severe-profound delay or were deceased, but only 19 of 64 (30%) infants with WS, "WS-like," or "unifocal epilepsy" had severe-profound delay, and only two of 64 (3%) were deceased.
Significance:
Three quarters of severe epilepsies of infancy could be assigned an epilepsy syndrome or "variant syndrome" at presentation. In this era of genomic testing and advanced brain imaging, diagnosing epilepsy syndromes at presentation remains clinically useful for guiding etiologic investigation, initial treatment, and prognostication.
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