{"doi":"10.1111/epi.17850","title":"Severe communication delays are independent of seizure burden and persist despite contemporary treatments in <i>SCN1A</i>+ Dravet syndrome: Insights from the <scp>ENVISION</scp> natural history study","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 ≤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.","journal":"Epilepsia","year":2023,"id":328185,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9684,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":154477,"name":"Ingrid E Scheffer","orcid":"0000-0002-2311-2174","position":1,"is_corresponding":false},{"id":724727,"name":"Joseph Sullivan","orcid":"0000-0003-2081-8988","position":2,"is_corresponding":false},{"id":844294,"name":"Andreas Brunklaus","orcid":"0000-0002-7728-6903","position":3,"is_corresponding":false},{"id":1049555,"name":"Susana Boronat","orcid":"0000-0001-7096-5578","position":4,"is_corresponding":false},{"id":451168,"name":"James W. Wheless","orcid":"0000-0002-4735-3431","position":5,"is_corresponding":false},{"id":463262,"name":"Linda Laux","orcid":"0000-0002-1429-2206","position":6,"is_corresponding":false},{"id":317102,"name":"Anup D. Patel","orcid":"0000-0001-9313-1541","position":7,"is_corresponding":false},{"id":1050127,"name":"Colin Roberts","orcid":null,"position":8,"is_corresponding":false},{"id":297275,"name":"Dennis Dlugos","orcid":"0000-0003-3088-7645","position":9,"is_corresponding":false},{"id":892614,"name":"Deborah Holder","orcid":"0000-0001-5532-4764","position":10,"is_corresponding":false},{"id":864883,"name":"Kelly G. Knupp","orcid":"0000-0002-1967-0827","position":11,"is_corresponding":false},{"id":1050128,"name":"Matt Lallas","orcid":null,"position":12,"is_corresponding":false},{"id":1049556,"name":"Steven Phillips","orcid":"0009-0007-4704-2258","position":13,"is_corresponding":false},{"id":311439,"name":"Eric Segal","orcid":"0000-0002-9986-6394","position":14,"is_corresponding":false},{"id":1050129,"name":"Patricia Smeyers","orcid":null,"position":15,"is_corresponding":false},{"id":297266,"name":"Dennis Lal","orcid":"0000-0002-5173-9636","position":16,"is_corresponding":false},{"id":154990,"name":"Elaine C Wirrell","orcid":"0000-0003-3015-8282","position":17,"is_corresponding":false},{"id":236855,"name":"Sameer M. Zuberi","orcid":"0000-0002-4489-4697","position":18,"is_corresponding":false},{"id":324678,"name":"Tobias Brünger","orcid":null,"position":19,"is_corresponding":false},{"id":1049557,"name":"Mary Wojnaroski","orcid":"0009-0006-5595-0419","position":20,"is_corresponding":false},{"id":1050130,"name":"B. Maru","orcid":null,"position":21,"is_corresponding":false},{"id":1050131,"name":"Penrose O'Donnell","orcid":null,"position":22,"is_corresponding":false},{"id":1050132,"name":"Magda F. Morton","orcid":null,"position":23,"is_corresponding":false},{"id":1049558,"name":"Emma S. James","orcid":"0000-0003-2672-9652","position":24,"is_corresponding":false},{"id":1049559,"name":"Maria Candida Vila","orcid":"0000-0003-4593-5822","position":25,"is_corresponding":false},{"id":299946,"name":"Norman Huang","orcid":null,"position":26,"is_corresponding":false},{"id":449137,"name":"Jacqueline S. Gofshteyn","orcid":"0000-0003-3354-6176","position":27,"is_corresponding":false},{"id":1049560,"name":"Salvador Rico","orcid":"0000-0002-1508-8717","position":28,"is_corresponding":false},{"id":154465,"name":"M. Scott Perry","orcid":"0000-0002-1825-846X","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T01:08:52.196069Z","pmid":"38049202","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}