Evolution and course of early life developmental encephalopathic epilepsies: Focus on Lennox-Gastaut syndrome

Epilepsia. 2018 Nov;59(11):2096-2105. doi: 10.1111/epi.14569. Epub 2018 Sep 26.

Abstract

Objectives: Developmental encephalopathic epilepsies (DEEs) are characterized by refractory seizures, disability, and early death. Opportunities to improve care and outcomes focus on West syndrome/infantile spasms (WS/IS). Lennox-Gastaut syndrome (LGS) is almost as common but receives little attention. We examined initial presentations of DEEs and their evolution over time to identify risk and indicators of developing LGS.

Methods: Data are from the Connecticut Study of Epilepsy, a prospective, longitudinal study of 613 children with newly diagnosed epilepsy recruited in 1993-1997. Central review of medical records permitted classification of epilepsy syndromes at diagnosis and at reclassification 2, 5, and 9 years later. DEEs were compared to other epilepsies for seizure and cognitive outcomes and mortality. Analyses examined the evolution of DEE syndromes after initial presentation, with specific comparisons made between WS/IS and LGS. Statistical analyses were performed with t tests and chi-square tests.

Results: Fifty-eight children (9.4%) had DEEs, median onset age = 1.1 years (interquartile range ([IQR] 0.3-1.3) in DEEs and 6.0 years (IQR 3.0-9.0) in other epilepsies (P < 0.001). DEEs vs other epilepsies had more pharmacoresistance (71% vs 18%), intellectual disability (84% vs 11%), and mortality (21% vs <1%; all P < 0.001). During follow-up, the form of epilepsy evolved in 33 children. WS/IS was the most common initial diagnosis (N = 23) and in 5 children WS/IS evolved later. LGS was diagnosed initially in 4 children (1 later revised) and in 22 by the end of follow-up, including 7 evolving from WS/IS and 12 from nonsyndromic generalized, focal, or undetermined epilepsies. Evolution to LGS took a median of 1.9 years. LGS developed in 13% of infants, including 9% of those who did not present initially with WS/IS.

Significance: DEEs account for disproportionate amounts of pharmacoresistance, disability, and early mortality. LGS often has a window between initial presentation and full expression. LGS should become targeted for early detection and prevention.

Keywords: West syndrome; infantile spasms; prevention; prognosis.

Publication types

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

MeSH terms

  • Age of Onset
  • Brain Diseases / complications*
  • Child
  • Child, Preschool
  • Cognition Disorders / etiology
  • Cohort Studies
  • Developmental Disabilities / etiology*
  • Electroencephalography
  • Epilepsy / complications*
  • Female
  • Humans
  • Infant
  • Lennox Gastaut Syndrome / epidemiology
  • Lennox Gastaut Syndrome / physiopathology*
  • Male