{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:46:08Z","timestamp":1787204768692,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["3K23NS107646\u201005S1"],"award-info":[{"award-number":["3K23NS107646\u201005S1"]}],"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":["5K23NS107646"],"award-info":[{"award-number":["5K23NS107646"]}],"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"}]},{"DOI":"10.13039\/501100020265","name":"Stan Perron Charitable Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Background<\/jats:bold>\n                    : CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy (DEE) associated with multiple impairments and comorbidities. Outcome measures for disease\u2010modifying clinical trials for DEEs should measurably capture a spectrum of caregiver priorities and be externally validated.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods<\/jats:bold>\n                    : The International CDKL5 Clinical Research Network was the data source for this observational study. A Structural Equation Model was constructed with latent, exogenous variables related to observed clinical features to calculate a global severity score from the following assessments: the CDKL5 Clinical Severity Assessment\u2010Clinician and \u2010Caregiver, Communication and Symbolic Behavior Scales Developmental Profile Infant Toddler Checklist and the Sleep Disturbance Scale for Children. Quantitative EEG power was measured as a biomarker. The Quality of Life Inventory\u2014Disability measured quality of life.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    : Acceptable fit statistics for models were obtained using data from 206 subjects (median [range] age 6.8 [3 months to 40] years). Motor and communication measures were the most important weighted contributors to the global severity score which correlated well with the biomarker and quality of life to support external validation.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions<\/jats:bold>\n                    : The resultant global severity score provided evidence that the assessments formed a coherent set of measures that reliably and meaningfully captured the diversity of severity in CDD. The models illustrated how the symptoms form a measurable network of relationships which may be suitable as an outcome measure for CDD and DEEs more broadly in clinical trials.\n                  <\/jats:p>","DOI":"10.1002\/brb3.71061","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T12:01:13Z","timestamp":1763121673000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Beyond Seizures as an Outcome Measure: A Global Severity Scoring System for CDKL5 Deficiency Disorder"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5092-7697","authenticated-orcid":false,"given":"Peter","family":"Jacoby","sequence":"first","affiliation":[{"name":"Centre for Child Health Research, The Kids Research Institute Australia The University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3264-0902","authenticated-orcid":false,"given":"Eric D.","family":"Marsh","sequence":"additional","affiliation":[{"name":"Division of Child Neurology, Departments of Neurology and Pediatrics Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania Philadelphia Pennsylvania United\u00a0States"}],"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 and Neurology, School of Medicine, University of Colorado, Precision Medicine Institute Children's Hospital Colorado Aurora Colorado United\u00a0States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4638-6589","authenticated-orcid":false,"given":"Jacinta M.","family":"Saldaris","sequence":"additional","affiliation":[{"name":"Centre for Child Health Research, The Kids Research Institute Australia The University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6405-5834","authenticated-orcid":false,"given":"Helen","family":"Leonard","sequence":"additional","affiliation":[{"name":"Centre for Child Health Research, The Kids Research Institute Australia The University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5385-0119","authenticated-orcid":false,"given":"Heather E.","family":"Olson","sequence":"additional","affiliation":[{"name":"Division of Epilepsy and Clinical Neurophysiology and Epilepsy Genetics Program, Department of Neurology Boston Children's Hospital Boston Massachusetts United\u00a0States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joni N.","family":"Saby","sequence":"additional","affiliation":[{"name":"Division of Child Neurology, Departments of Neurology and Pediatrics Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania Philadelphia Pennsylvania United\u00a0States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9068-4167","authenticated-orcid":false,"given":"Elia","family":"Pestana\u2010Knight","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Neurological Department Epilepsy Center Cleveland Ohio United\u00a0States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9685-7118","authenticated-orcid":false,"given":"Rajsekar","family":"Rajaraman","sequence":"additional","affiliation":[{"name":"UCLA Mattel Children's Hospital Los Angeles California United\u00a0States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3969-6394","authenticated-orcid":false,"given":"Dana","family":"Price","sequence":"additional","affiliation":[{"name":"NYU Langone Health and Department of Neurology New York University New York New York United\u00a0States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2031-7278","authenticated-orcid":false,"given":"Judith","family":"Weisenberg","sequence":"additional","affiliation":[{"name":"St. Louis Children's Hospital and Washington University School of Medicine St Louis Missouri United\u00a0States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0127-7322","authenticated-orcid":false,"given":"Bernhard","family":"Suter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics &amp; Neurology Baylor College of Medicine Houston Texas 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