目的:本研究旨在通过回顾性研究验证一组癫痫发作易感性的候选生物标志物,多点病例对照研究,并确定从常规收集的脑电图(EEG)中大量队列(包括癫痫和常见的替代疾病,例如非癫痫发作障碍)中得出的这些生物标志物的稳健性。
方法:数据库由来自648名受试者的814个脑电图记录组成,从英国八个国家卫生服务机构收集。临床非贡献脑电图记录由经验丰富的临床科学家鉴定(N=281;152替代条件,129癫痫)。八个计算标记(光谱[n=2],基于网络的[n=4],和基于模型的[n=2])在每个记录中计算。使用两层交叉验证方法开发了基于集成的分类器。我们使用标准回归方法来评估潜在的混杂变量(例如,年龄,性别,治疗状态,合并症)影响模型性能。
结果:我们发现,在具有临床非贡献性正常脑电图的队列中,平衡准确率为68%(灵敏度=61%,特异性=75%,阳性预测值=55%,阴性预测值=79%,诊断比值比=4.64,接受者操作特征曲线下面积=0.72)。小组水平分析发现,没有证据表明任何潜在的混杂变量显着影响整体绩效。
结论:这些结果提供了证据,表明该组生物标志物可以为临床决策提供额外价值,为减少诊断延迟和误诊率的决策支持工具提供基础。因此,未来的工作应该评估在精心设计的前瞻性研究中利用这些生物标志物时诊断产量和诊断时间的变化。
OBJECTIVE: This study was undertaken to validate a set of candidate biomarkers of seizure susceptibility in a retrospective, multisite
case-control study, and to determine the robustness of these biomarkers derived from routinely collected electroencephalography (EEG) within a large cohort (both epilepsy and common alternative conditions such as nonepileptic attack disorder).
METHODS: The database consisted of 814 EEG recordings from 648 subjects, collected from eight National Health Service sites across the UK. Clinically noncontributory EEG recordings were identified by an experienced clinical scientist (N = 281; 152 alternative conditions, 129 epilepsy). Eight computational markers (spectral [n = 2],
network-based [n = 4], and model-based [n = 2]) were calculated within each recording. Ensemble-based classifiers were developed using a two-tier cross-validation approach. We used standard regression methods to assess whether potential confounding variables (e.g., age, gender, treatment status, comorbidity) impacted model performance.
RESULTS: We found levels of balanced accuracy of 68% across the cohort with clinically noncontributory normal EEGs (sensitivity =61%, specificity =75%, positive predictive value =55%, negative predictive value =79%, diagnostic odds ratio =4.64, area under receiver operated characteristics curve =.72). Group level analysis found no evidence suggesting any of the potential confounding variables significantly impacted the overall performance.
CONCLUSIONS: These results provide evidence that the set of biomarkers could provide additional value to clinical decision-making, providing the foundation for a decision support tool that could reduce diagnostic delay and misdiagnosis rates. Future work should therefore assess the change in diagnostic yield and time to diagnosis when utilizing these biomarkers in carefully designed prospective studies.