Language

English

Publication Date

10-1-2024

Journal

Epilepsia

DOI

10.1111/epi.18094

PMID

39190322

PMCID

PMC11495992

PubMedCentral® Posted Date

10-1-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Objective: The CDKL5 Clinical Severity Assessment (CCSA) is a comprehensive, content-validated measurement tool capturing the diverse challenges of cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD), a genetically caused developmental epileptic encephalopathy (DEE). The CCSA is divided into clinician-reported (CCSA-Clinician) and caregiver-reported (CCSA-Caregiver) assessments. The aim of this study was to evaluate the factor structure of these measures through confirmatory factor analysis (CFA) and evaluate their validity and reliability.

Methods: Participants were recruited from the International CDKL5 Clinical Research Network to take part in an in-clinic CCSA-Clinician evaluation (n = 148) and/or complete the CCSA-Caregiver questionnaire (n = 198). CFA was used to determine domains, and factor loadings and validity were assessed. For the CCSA-Clinician, inter-rater reliability was assessed by nine CDD experienced clinicians via 14 pre-recorded evaluations. Eight clinicians re-viewed and re-scored the videos after 4 weeks to evaluate intra-rater reliability. The CCSA-Caregiver was completed on a second occasion by 34 caregivers after 2-4 weeks to assess test-retest reliability.

Results: CFA resulted in three domains for the CCSA-Clinician (motor and movement, communication, vision) and four domains for the CCSA-Caregiver (seizures, behavior, alertness, feeding), with good item loadings across both measures. Structural statistics, internal consistency, discriminant validity, and reliability were satisfactory for both measures, and scores were consistent between known groups.

Significance: This study provides strong evidence that the CCSA measures are suitable to assess the clinical severity of individuals with CDD, supporting their use in clinical trials. Further evaluation of responsiveness to change in a longitudinal assessment is planned. Use may also be appropriate in similar DEEs but would require validation in those populations.

Keywords

Adolescent, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Caregivers, Child Behavior, Epileptic Syndromes, Physicians, Psychometrics, Reproducibility of Results, Severity of Illness Index, Spasms, Infantile, Surveys and Questionnaires, Developmental epileptic encephalopathy, Clinical outcome assessment, Confirmatory factor analysis, Validity, Reliability

Published Open-Access

yes

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