Leonard Helen, Junaid Mohammed, Wong Kingsley, Aimetti Alex A, Pestana Knight Elia, Downs Jenny
Telethon Kids Institute, University of Western Australia, Nedlands, Western Australia, Australia.
Faculty of Health and Medical Sciences, Centre of Child Health Research, University of Western Australia, Nedlands, Western Australia, Australia.
Epilepsia. 2022 Feb;63(2):352-363. doi: 10.1111/epi.17125. Epub 2021 Nov 27.
The study investigated the effect of seizure and medication burden at initial contact with the International CDKL5 Disorder Database on subsequent development and clinical severity and compared quality of life among those whose development progressed, remained stable, or regressed between baseline and follow-up.
The effects of seizure and medication burden at baseline (high or low) on the CDKL5 Disorder Severity Scores and CDKL5 Developmental Score (CDS) at follow-up were assessed using linear and negative binomial regressions, respectively, with adjustment for age at baseline, gender, and follow-up duration with and without genotype. Seizure and medication burden were defined by average daily seizure count (high, ≥5/day; low, <5/day) and number of antiseizure medications (high, ≥3/day; low, <3/day), respectively. The effects of change in CDS over time (improved, stable, or deteriorated) on Quality of Life Inventory-Disability (QI-Disability) total and domain scores at follow-up were assessed in those aged at least 3 years at follow-up using linear regression models with adjustment for baseline CDS, gender, and follow-up duration.
The expected follow-up CDS was lower for individuals with high compared to low seizure burden at baseline (β = -.49, 95% confidence interval [CI] = -.84 to -.13). The average total QI-Disability score was 5.6 (95% CI = -.2 to 11.5) points higher among those with improved compared with stable or deteriorating CDS and 8.5 (95% CI = 3.1-13.8) points lower for those with deteriorating compared to stable or improved CDS.
Our finding that later development showed slight improvement in those with better earlier seizure control even after adjustment for genotype suggests that the trajectory for an individual child is not necessarily predetermined and could possibly be influenced by optimal seizure management. This has implications for children's quality of life.
本研究调查了初次接触国际CDKL5障碍数据库时的癫痫发作和药物负担对后续发育及临床严重程度的影响，并比较了在基线和随访期间发育进展、保持稳定或倒退的患者的生活质量。
分别采用线性回归和负二项回归评估基线时（高或低）癫痫发作和药物负担对随访时CDKL5障碍严重程度评分和CDKL5发育评分（CDS）的影响，并对基线年龄、性别以及有无基因型的随访时间进行校正。癫痫发作和药物负担分别由平均每日癫痫发作次数（高，≥5次/天；低，<5次/天）和抗癫痫药物数量（高，≥3种/天；低，<3种/天）定义。在随访时年龄至少3岁的患者中，采用线性回归模型评估随访时CDS随时间的变化（改善、稳定或恶化）对生活质量量表-残疾（QI-残疾）总分及各领域得分的影响，并对基线CDS、性别和随访时间进行校正。
与基线时癫痫发作负担低的个体相比，癫痫发作负担高的个体预期随访CDS更低（β = -0.49，95%置信区间[CI] = -0.84至-0.13）。与CDS稳定或恶化的患者相比，CDS改善的患者平均QI-残疾总分高5.6分（95%CI = -0.2至11.5），与CDS稳定或改善的患者相比，CDS恶化的患者平均QI-残疾总分低8.5分（95%CI = 3.1 - 13.8）。
我们的研究发现，即使在对基因型进行校正后，早期癫痫控制较好的个体后期发育仍有轻微改善，这表明个体儿童的发育轨迹不一定是预先确定的，可能会受到最佳癫痫管理的影响。这对儿童的生活质量具有重要意义。
