Severe communication delays are independent of seizure burden and persist despite contemporary treatments in SCN1A+ Dravet syndrome: Insights from the ENVISION natural history study.

Autor: Perry MS; Cook Children's Medical Center, Fort Worth, Texas, USA., Scheffer IE; University of Melbourne, Austin Health, Melbourne, Victoria, Australia., Sullivan J; University of California, San Francisco, San Francisco, California, USA., Brunklaus A; School of Health & Wellbeing, University of Glasgow, Glasgow, UK., Boronat S; Hospital de la Santa Creu i Sant Pau, Barcelona, Spain., Wheless JW; Le Bonheur Children's Hospital, Memphis, Tennessee, USA., Laux L; Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA., Patel AD; Nationwide Children's Hospital, Columbus, Ohio, USA., Roberts CM; Doernbecher Children's Hospital, Portland, Oregon, USA., Dlugos D; Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Holder D; Cedars-Sinai Medical Center, Los Angeles, California, USA., Knupp KG; Children's Hospital Colorado, Aurora, Colorado, USA., Lallas M; Nicklaus Children's Hospital, Miami, Florida, USA., Phillips S; Multicare Health System, Tacoma, Washington, USA., Segal E; Northeast Regional Epilepsy Group & Hackensack University Medical Center, Hackensack Meridian School of Medicine, Hackensack, New Jersey, USA., Smeyers P; Hospital Universitari i Politècnic la Fe, Valencia, Spain., Lal D; UTHealth Houston, Houston, Texas, USA., Wirrell E; Mayo Clinic, Rochester, Minnesota, USA., Zuberi S; School of Health & Wellbeing, University of Glasgow, Glasgow, UK., Brünger T; UTHealth Houston, Houston, Texas, USA., Wojnaroski M; Nationwide Children's Hospital, Columbus, Ohio, USA., Maru B; SSI Strategy, London, UK., O'Donnell P; Encoded Therapeutics, South San Francisco, California, USA., Morton M; Encoded Therapeutics, South San Francisco, California, USA., James E; Encoded Therapeutics, South San Francisco, California, USA., Vila MC; Encoded Therapeutics, South San Francisco, California, USA., Huang N; Encoded Therapeutics, South San Francisco, California, USA., Gofshteyn JS; Encoded Therapeutics, South San Francisco, California, USA., Rico S; Encoded Therapeutics, South San Francisco, California, USA.
Jazyk: angličtina
Zdroj: Epilepsia [Epilepsia] 2024 Feb; Vol. 65 (2), pp. 322-337. Date of Electronic Publication: 2023 Dec 22.
DOI: 10.1111/epi.17850
Abstrakt: Objective: Dravet syndrome (DS) is a developmental and epileptic encephalopathy characterized by high seizure burden, treatment-resistant epilepsy, and developmental stagnation. Family members rate communication deficits among the most impactful disease manifestations. We evaluated seizure burden and language/communication development in children with DS.
Methods: ENVISION was a prospective, observational study evaluating children with DS associated with SCN1A pathogenic variants (SCN1A+ DS) enrolled at age ≤5 years. Seizure burden and antiseizure medications were assessed every 3 months and communication and language every 6 months with the Bayley Scales of Infant and Toddler Development 3rd edition and the parent-reported Vineland Adaptive Behavior Scales 3rd edition. We report data from the first year of observation, including analyses stratified by age at Baseline: 0:6-2:0 years:months (Y:M; youngest), 2:1-3:6 Y:M (middle), and 3:7-5:0 Y:M (oldest).
Results: Between December 2020 and March 2023, 58 children with DS enrolled at 16 sites internationally. Median follow-up was 17.5 months (range = .0-24.0), with 54 of 58 (93.1%) followed for at least 6 months and 51 of 58 (87.9%) for 12 months. Monthly countable seizure frequency (MCSF) increased with age (median [minimum-maximum] = 1.0 in the youngest [1.0-70.0] and middle [1.0-242.0] age groups and 4.5 [.0-2647.0] in the oldest age group), and remained high, despite use of currently approved antiseizure medications. Language/communication delays were observed early, and developmental stagnation occurred after age 2 years with both instruments. In predictive modeling, chronologic age was the only significant covariate of seizure frequency (effect size = .52, p = .024). MCSF, number of antiseizure medications, age at first seizure, and convulsive status epilepticus were not predictors of language/communication raw scores.
Significance: In infants and young children with SCN1A+ DS, language/communication delay and stagnation were independent of seizure burden. Our findings emphasize that the optimal therapeutic window to prevent language/communication delay is before 3 years of age.
(© 2023 Encoded Therapeutics. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
Databáze: MEDLINE
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