Severe Communication Delays Are Independent of Seizure Burden and Persist Despite Contemporary Treatments in SCN1A+ Dravet Syndrome: Insights from the ENVISION Natural History Study.

Data de publicació: 04/12/2023 Data Ahead of Print: 04/12/2023

Autors de IIS La Fe

• Patricia Smeyers Dura

  Autor

Autors aliens a IIS La Fe

• Perry, M. Scott
• Scheffer, Ingrid E.
• Sullivan, Joseph
• Brunklaus, Andreas
• Boronat, Susana
• Wheless, James W.
• Laux, Linda
• Patel, Anup D.
• Roberts, Colin M.
• Dlugos, Dennis
• Holder, Deborah
• Knupp, Kelly G.
• Lallas, Matt
• Phillips, Steven
• Segal, Eric
• Lal, Dennis
• Wirrell, Elaine
• Zuberi, Sameer
• Brunger, Tobias
• Wojnaroski, Mary
• Maru, Benit
• O'Donnell, Penrose
• Morton, Magda
• James, Emma
• Vila, Maria Candida
• Huang, Norman
• Gofshteyn, Jacqueline S.
• Rico, Salvador

Abstract

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 <5years. 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 (BSID-III) and the parent-reported Vineland Adaptive Behavior Scales 3rd Edition (VABS-III). We report data from the first year of observation, including analyses stratified by age at Baseline: 0:6-2:0years:months (youngest), 2:1-3:6years:months (middle) and 3:7-5:0years:months (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: 0.0-24.0), with 54/58 (93.1%) followed for at least 6 months and 51/58 (87.9%) for 12 months. Monthly countable seizure frequency (MCSF) increased with age (median [min-max]: 1.0 in the youngest [1.0-70.0] and middle [1.0-242.0] age groups and 4.5 [0.0-2647.0] 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 2years with both instruments. In predictive modeling, chronologic age was the only significant covariate of seizure frequency (effect size 0.52, P=0.024). 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 the optimal therapeutic window to prevent language/communication delay is before 3years of age.

© 2023 Encoded Therapeutics. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.

Keywords

• Dravet syndrome; ENVISION; communication/language delays; developmental and epileptic encephalopathy; natural history study