Telethon Kids Institute, Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia.
Curtin School of Allied Health, Curtin University, Perth, Western Australia, Australia.
Epilepsia. 2024 Oct;65(10):3064-3075. doi: 10.1111/epi.18094. Epub 2024 Aug 27.
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.
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.
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.
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.
CDKL5 临床严重程度评估（CCSA）是一种全面、内容验证的测量工具，可捕捉细胞周期蛋白依赖性激酶样 5（CDKL5）缺乏症（CDD）的各种挑战，CDD 是一种遗传性发育性癫痫性脑病（DEE）。CCSA 分为临床医生报告（CCSA-临床医生）和护理人员报告（CCSA-护理人员）评估。本研究的目的是通过验证性因子分析（CFA）评估这些测量方法的因子结构，并评估其有效性和可靠性。
参与者从国际 CDKL5 临床研究网络招募，参与门诊 CCSA-临床医生评估（n=148）和/或完成 CCSA-护理人员问卷（n=198）。CFA 用于确定领域，评估因子负荷和有效性。对于 CCSA-临床医生，9 位具有 CDD 经验的临床医生通过 14 个预先录制的评估来评估内部评估者信度。8 位临床医生在 4 周后重新查看和重新评分视频，以评估内部评估者信度。34 位护理人员在 2-4 周后再次完成 CCSA-护理人员，以评估测试-重测信度。
CCSA-临床医生的 CFA 结果为三个领域（运动和运动、沟通、视力）和 CCSA-护理人员的四个领域（癫痫发作、行为、警觉、喂养），两个测量结果的项目负荷都很好。结构统计数据、内部一致性、判别有效性和可靠性在两个测量结果中均令人满意，并且在已知组之间得分一致。
本研究为 CCSA 测量方法适合评估 CDD 个体的临床严重程度提供了有力证据，支持其在临床试验中的使用。计划进一步评估在纵向评估中对变化的反应性。在其他类似的 DEE 中也可能适用，但需要在这些人群中验证。
