Epilepsy Is Heterogeneous in Early-Life Tuberous Sclerosis Complex

Pediatr Neurol. 2021 Oct:123:1-9. doi: 10.1016/j.pediatrneurol.2021.06.012. Epub 2021 Jul 6.


Background: Epilepsy in tuberous sclerosis complex (TSC) typically presents with early onset, multiple seizure types, and intractability. However, variability is observed among individuals. Here, detailed individual data on seizure characteristics collected prospectively during early life were used to define epilepsy profiles in this population.

Methods: Children aged zero to 36 months were followed longitudinally. Caregivers kept daily seizure diaries, including onset and daily counts for each seizure type. Patients with >70% seizure diary completion and >365 diary days were included. Developmental outcomes at 36 months were compared between subgroups.

Results: Epilepsy was seen in 124 of 156 (79%) participants. Seizure onset occurred from zero to 29.5 months; 93% had onset before age 12 months. Focal seizures and epileptic spasms were most common. Number of seizures (for median 897 days) ranged from 1 to 9128. Hierarchical clustering based on six metrics of seizure burden (age of onset, total seizures, ratio of seizure days to nonseizure days, seizures per seizure day, and worst seven- and 30-day stretches) revealed two distinct groups with broadly favorable and unfavorable epilepsy profiles. Subpopulations within each group showed clinically meaningful differences in seizure burden. Groups with higher seizure burden had worse developmental outcomes at 36 months.

Conclusions: Although epilepsy is highly prevalent in TSC, not all young children with TSC have the same epilepsy profile. At least two phenotypic subpopulations are discernible based on seizure burden. Early and aggressive treatments for epilepsy in TSC may be best leveraged by targeting specific subgroups based on phenotype severity.

Keywords: Epilepsy in infancy; Epilepsy phenotype; Epileptic spasms; Focal seizures; Seizure burden; Seizure diary; Tubers.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age of Onset
  • Child, Preschool
  • Epilepsies, Partial / etiology
  • Epilepsies, Partial / physiopathology
  • Epilepsy / etiology*
  • Epilepsy / physiopathology*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Longitudinal Studies
  • Male
  • Spasms, Infantile / etiology
  • Spasms, Infantile / physiopathology
  • Tuberous Sclerosis / complications*