Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
Epilepsy Behav. 2022 Mar;128:108586. doi: 10.1016/j.yebeh.2022.108586. Epub 2022 Feb 11.
Developmental and epileptic encephalopathies (DEE) entail moderate to profound communication and other impairments that are poorly measured by typical clinical outcomes assessments (COA). We examined the potential of alternative approaches, specifically, the use of raw scores and COAs outside of their intended age ranges.
In a cross-sectional survey, 120 parents of children with Dravet Syndrome, Lennox-Gastaut syndrome, KCNQ2-DEE, KCNB1-DEE, and SCN2A-DEE (ages 1-35 years) completed the Adaptive Behavior Assessment System-3 for ages 0-5 years, modified checklist for autism (mCHAT), communication and social behavior scales (CSBS), communication matrix (CM), and several parent-reported classifiers of communication. Adaptive Behavior Assessment System communication and social raw scores were the primary and adjunctive outcomes. Floor and ceiling effects, dispersion and convergence with related measures were assessed with appropriate parametric and nonparametric statistical techniques.
Median chronological age (CA) was 8.7 years (Interquartile range (IQR): 5.3-13.5). Adaptive Behavior Assessment Systemcommunication and social age equivalents were 12.5 months (IQR 7.5-28) and 16.5 months (IQR 9-31). Most raw scores corresponded to standardized scores indicating performance <3 standard deviations below the general population mean. Adaptive Behavior Assessment System raw scores demonstrated minimal floor and ceiling effects (<1-2.5%). In linear regression models, scores correlated with age under 6 years (communication, p = 0.001; social, p = 0.003) but significantly flattened out thereafter. Scores varied substantially by DEE group (both p < 0.001) and decreased with higher convulsive seizure frequency (communication, p = 0.01, social, p = 0.02). There was good convergence with mCHAT, CSBS, and CM scores (all r > 0.8).
Raw scores and out-of-range COAs may provide measures that are sensitive at the very limited levels of functioning typical of profoundly impaired, older patients with DEEs. To ensure that targeted trial outcomes are responsive to meaningful change, development of these approaches will be essential to clinical trial readiness for novel therapies for rare DEEs.
发育性和癫痫性脑病（DEE）需要中度至重度的交流和其他障碍，这些障碍用典型的临床结果评估（COA）很难衡量。我们研究了替代方法的潜力，特别是在其预期年龄范围之外使用原始分数和 COA。
在一项横断面调查中，120 名患有德拉维特综合征、 Lennox-Gastaut 综合征、KCNQ2-DEE、KCNB1-DEE 和 SCN2A-DEE 的儿童的父母（年龄 1-35 岁）完成了适用于 0-5 岁的适应性行为评估系统-3、改良自闭症检查表（mCHAT）、沟通和社会行为量表（CSBS）、沟通矩阵（CM）以及几个家长报告的沟通分类器。适应性行为评估系统沟通和社会原始分数是主要和辅助结果。使用适当的参数和非参数统计技术评估地板和天花板效应、与相关测量值的离散度和收敛性。
中位年龄（CA）为 8.7 岁（四分位距（IQR）：5.3-13.5）。适应性行为评估系统沟通和社会年龄等价物分别为 12.5 个月（IQR 7.5-28）和 16.5 个月（IQR 9-31）。大多数原始分数与标准化分数相对应，表明表现低于一般人群平均值 3 个标准差以下。适应性行为评估系统原始分数显示出最小的地板和天花板效应（<1-2.5%）。在线性回归模型中，得分与 6 岁以下的年龄相关（沟通，p=0.001；社交，p=0.003），但此后明显趋于平缓。得分因 DEE 组而异（均 p<0.001），且随着癫痫发作频率的增加而降低（沟通，p=0.01，社交，p=0.02）。与 mCHAT、CSBS 和 CM 评分具有良好的一致性（均 r>0.8）。
原始分数和超出范围的 COA 可能提供敏感的测量值，适用于功能严重受损的 DEE 患者的非常有限的水平。为确保靶向试验结果对有意义的变化做出反应，开发这些方法对于针对罕见 DEE 的新型疗法的临床试验准备至关重要。
