Nonseizure consequences of Dravet syndrome, KCNQ2-DEE, KCNB1-DEE, Lennox–Gastaut syndrome, ESES: A functional framework

Anne T. Berg*, Deborah Gaebler-Spira, Greta Wilkening, Frank Zelko, Kelly Knupp, Tracy Dixon-Salazar, Nicole Villas, Mary Anne Meskis, Vinez Harwell, Tina Thompson, Scotty Sims, Gerry Nesbitt

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Rationale: Developmental epilepsies and encephalopathies (DEEs) are characterized by many severe developmental impairments, which are not well-described. A functional framework could facilitate understanding of their nature and severity and guide the selection instruments to measure improvements in therapeutic trials. Methods: An online survey administered through several parent-organized foundations utilized accepted functional classifications and questionnaires derived from common instruments to determine levels of mobility, fine motor, communication, and feeding functions. Statistical analyses focused on overall levels of function and across-group comparisons adjusted for age. Results: From 6/2018 to 2/2020, 252 parents provided information for one or more functional domains. Median age was 7.2 years (interquartile range (IQR): 3.9 to 11.8), and 128 (51%) were females. DEE groups were Dravet syndrome (N = 72), KCNQ2-DEE (N = 80), KCNB1-DEE, (N = 33), Lennox–Gastaut syndrome (LGS; N = 26), electrographic status epilepticus in sleep (ESES; N = 15), and others (N = 26). Overall, functional hand grasp was absent in 48 (20%). Of children ≥ 2 years old, 60/214 (28%) could not walk independently, 85 (40%) were dependent on someone else for feeding, and 153 (73%) did not effectively communicate with unfamiliar people. Impairments entailing absence or near absence of independent function (profound impairment) were observed in 0, 1, 2, 3, and 4 domains for 58 (25%), 78 (34%), 40 (17%), 33 (14%), and 22 (10%) children, respectively. After adjustment for age, impairment levels varied substantially across DEE group for mobility (p < 0.0001), feeding (p < 0.0001), communication (p < 0.0001), hand grasp (p < 0.0001), and number of profoundly impaired domains (p < 0.0001). Three or four profoundly affected domains were reported in 44% of KCNQ2-DEE participants, followed by LGS (29%), KCNB1-DEE (27%), ESES (7%), and Dravet syndrome (6%). Conclusions: Many children with DEEs experience severe functional impairments, and few children have typical function. As precision therapies will emphasize nonseizures consequences of DEEs, understanding the nature of abilities and impairments will be critical to selecting appropriate outcome measures in therapeutic trials.

Original languageEnglish (US)
Article number107287
JournalEpilepsy and Behavior
Volume111
DOIs
StatePublished - Oct 2020

Keywords

  • Epilepsy
  • Functional ability
  • Outcome measures
  • Precision medicine

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Behavioral Neuroscience

Fingerprint Dive into the research topics of 'Nonseizure consequences of Dravet syndrome, KCNQ2-DEE, KCNB1-DEE, Lennox–Gastaut syndrome, ESES: A functional framework'. Together they form a unique fingerprint.

Cite this