{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:08:23Z","timestamp":1789632503975,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T00:00:00Z","timestamp":1684108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100010091","name":"International Foundation for CDKL5 Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010091","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["1K23 NS107646\u201005"],"award-info":[{"award-number":["1K23 NS107646\u201005"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["U01NS114312"],"award-info":[{"award-number":["U01NS114312"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>We aimed to assess the treatment response of infantile\u2010onset epileptic spasms (ES) in CDKL5 deficiency disorder (CDD) vs other etiologies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated patients with ES from the CDKL5 Centers of Excellence and the National Infantile Spasms Consortium (NISC), with onset from 2\u2009months to 2\u2009years, treated with adrenocorticotropic hormone (ACTH), oral corticosteroids, vigabatrin, and\/or the ketogenic diet. We excluded children with tuberous sclerosis complex, trisomy 21, or unknown etiology with normal development because of known differential treatment responses. We compared the two cohorts for time to treatment and ES remission at 14\u2009days and 3\u2009months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We evaluated 59 individuals with CDD (79% female, median ES onset 6\u2009months) and 232 individuals from the NISC database (46% female, median onset 7\u2009months). In the CDD cohort, seizures prior to ES were common (88%), and hypsarrhythmia and its variants were present at ES onset in 34%. Initial treatment with ACTH, oral corticosteroids, or vigabatrin started within 1\u2009month of ES onset in 27 of 59 (46%) of the CDD cohort and 182 of 232 (78%) of the NISC cohort (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001). Fourteen\u2010day clinical remission of ES was lower for the CDD group (26%, 7\/27) than for the NISC cohort (58%, 106\/182, <jats:italic>p<\/jats:italic>\u2009=\u2009.0002). Sustained ES remission at 3\u2009months occurred in 1 of 27 (4%) of CDD patients vs 96 of 182 (53%) of the NISC cohort (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001). Comparable results were observed with longer lead time (\u22651\u2009month) or prior treatment. Ketogenic diet, used within 3\u2009months of ES onset, resulted in ES remission at 1\u2009month, sustained at 3\u2009months, in at least 2 of 13 (15%) individuals with CDD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Compared to the broad group of infants with ES, children with ES in the setting of CDD often experience longer lead time to treatment and respond poorly to standard treatments. Development of alternative treatments for ES in CDD is needed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17630","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T12:13:07Z","timestamp":1682683987000},"page":"1821-1832","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Epileptic spasms in CDKL5 deficiency disorder: Delayed treatment and poor response to first\u2010line therapies"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5385-0119","authenticated-orcid":false,"given":"Heather E.","family":"Olson","sequence":"first","affiliation":[{"name":"Division of Epilepsy and Clinical Neurophysiology and Epilepsy Genetics Program, Department of Neurology Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4544-3724","authenticated-orcid":false,"given":"Scott","family":"Demarest","sequence":"additional","affiliation":[{"name":"Department of Pediatrics School of Medicine, Children's Hospital Colorado, University of Colorado  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elia","family":"Pestana\u2010Knight","sequence":"additional","affiliation":[{"name":"Epilepsy Center, Neurological Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3123-5713","authenticated-orcid":false,"given":"Ahsan N.","family":"Moosa","sequence":"additional","affiliation":[{"name":"Epilepsy Center, Neurological Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Epilepsy Center, Neurological Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 R.","family":"P\u00e9rez\u2010P\u00e9rez","sequence":"additional","affiliation":[{"name":"Epilepsy Center, Neurological Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Weisenberg","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"O\u2019Connor\u00a0Prange","sequence":"additional","affiliation":[{"name":"Division of Child Neurology, Children's Hospital of Philadelphia, Departments of Neurology and Pediatrics, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric D.","family":"Marsh","sequence":"additional","affiliation":[{"name":"Division of Child Neurology, Children's Hospital of Philadelphia, Departments of Neurology and Pediatrics, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajsekar R.","family":"Rajaraman","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology David Geffen School of Medicine and UCLA Mattel Children's Hospital  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Suter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Neurology Baylor College of Medicine, Texas Children's Hospital, Houston  Houston Texas 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