TY - JOUR
T1 - Severe communication delays are independent of seizure burden and persist despite contemporary treatments in SCN1A+ Dravet syndrome
T2 - Insights from the ENVISION natural history study
AU - Perry, M. Scott
AU - Scheffer, Ingrid E.
AU - Sullivan, Joseph
AU - Brunklaus, Andreas
AU - Boronat, Susana
AU - Wheless, James W.
AU - Laux, Linda
AU - Patel, Anup D.
AU - Roberts, Colin M.
AU - Dlugos, Dennis
AU - Holder, Deborah
AU - Knupp, Kelly G.
AU - Lallas, Matt
AU - Phillips, Steven
AU - Segal, Eric
AU - Smeyers, Patricia
AU - Lal, Dennis
AU - Wirrell, Elaine
AU - Zuberi, Sameer
AU - Brünger, Tobias
AU - Wojnaroski, Mary
AU - Maru, Benit
AU - O'Donnell, Penrose
AU - Morton, Magda
AU - James, Emma
AU - Vila, Maria Candida
AU - Huang, Norman
AU - Gofshteyn, Jacqueline S.
AU - Rico, Salvador
N1 - Publisher Copyright:
© 2023 Encoded Therapeutics. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
PY - 2024/2
Y1 - 2024/2
N2 - 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.
AB - 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.
KW - communication/language delays
KW - developmental and epileptic encephalopathy
KW - Dravet syndrome
KW - ENVISION
KW - natural history study
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U2 - 10.1111/epi.17850
DO - 10.1111/epi.17850
M3 - Article
C2 - 38049202
AN - SCOPUS:85180661831
SN - 0013-9580
VL - 65
SP - 322
EP - 337
JO - Epilepsia
JF - Epilepsia
IS - 2
ER -