Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; O'Brien Institute for Public Health, University of Calgary, Calgary, AB, Canada; Centre for Health Informatics, University of Calgary, Calgary, AB, Canada.
UCL Institute of Health Informatics, London, UK; Health Data Research (HDR) UK, London, UK.
Seizure. 2023 Oct;111:58-67. doi: 10.1016/j.seizure.2023.07.016. Epub 2023 Jul 29.
Late-onset epilepsy is a heterogenous entity associated with specific aetiologies and an elevated risk of premature mortality. Specific multimorbid-socioeconomic profiles and their unique prognostic trajectories have not been described. We sought to determine if specific clusters of late onset epilepsy exist, and whether they have unique hazards of premature mortality.
We performed a retrospective observational cohort study linking primary and hospital-based UK electronic health records with vital statistics data (covering years 1998-2019) to identify all cases of incident late onset epilepsy (from people aged ≥65) and 1:10 age, sex, and GP practice-matched controls. We applied hierarchical agglomerative clustering using common aetiologies identified at baseline to define multimorbid-socioeconomic profiles, compare hazards of early mortality, and tabulating causes of death stratified by cluster.
From 1,032,129 people aged ≥65, we identified 1048 cases of late onset epilepsy who were matched to 10,259 controls. Median age at epilepsy diagnosis was 68 (interquartile range: 66-72) and 474 (45%) were female. The hazard of premature mortality related to late-onset epilepsy was higher than matched controls (hazard ratio [HR] 1.73; 95% confidence interval [95%CI] 1.51-1.99). Ten unique phenotypic clusters were identified, defined by 'healthy' males and females, ischaemic stroke, intracerebral haemorrhage (ICH), ICH and alcohol misuse, dementia and anxiety, anxiety, depression in males and females, and brain tumours. Cluster-specific hazards were often similar to that derived for late-onset epilepsy as a whole. Clusters that differed significantly from the base late-onset epilepsy hazard were 'dementia and anxiety' (HR 5.36; 95%CI 3.31-8.68), 'brain tumour' (HR 4.97; 95%CI 2.89-8.56), 'ICH and alcohol misuse' (HR 2.91; 95%CI 1.76-4.81), and 'ischaemic stroke' (HR 2.83; 95%CI 1.83-4.04). These cluster-specific risks were also elevated compared to those derived for tumours, dementia, ischaemic stroke, and ICH in the whole population. Seizure-related cause of death was uncommon and restricted to the ICH, ICH and alcohol misuse, and healthy female clusters.
Late-onset epilepsy is an amalgam of unique phenotypic clusters that can be quantitatively defined. Late-onset epilepsy and cluster-specific comorbid profiles have complex effects on premature mortality above and beyond the base rates attributed to epilepsy and cluster-defining comorbidities alone.
迟发性癫痫是一种与特定病因学相关的异质实体，且具有较高的过早死亡风险。目前尚未描述特定的多病种-社会经济特征及其独特的预后轨迹。我们试图确定迟发性癫痫是否存在特定的聚类，以及它们是否具有独特的过早死亡风险。
我们进行了一项回顾性观察性队列研究，将英国初级保健和医院的电子健康记录与生命统计数据（涵盖 1998-2019 年）相关联，以确定所有年龄在 65 岁及以上的新发迟发性癫痫病例（从年龄在 65 岁及以上的人群中），并按照年龄、性别和全科医生实践进行 1:10 的匹配，以确定对照组。我们应用基于基线确定的常见病因的分层聚集聚类来定义多病种-社会经济特征，比较早期死亡率的风险，并按聚类分层列出死因。
从 1032129 名年龄在 65 岁及以上的人群中，我们确定了 1048 例迟发性癫痫病例，并与 10259 名对照进行了匹配。癫痫诊断时的中位年龄为 68 岁（四分位距：66-72 岁），474 例（45%）为女性。与迟发性癫痫相关的过早死亡风险高于匹配对照组（风险比[HR] 1.73；95%置信区间[95%CI] 1.51-1.99）。确定了 10 个独特的表型聚类，这些聚类由“健康”男性和女性、缺血性中风、脑出血（ICH）、ICH 和酒精滥用、痴呆和焦虑、焦虑、男性和女性的抑郁以及脑瘤定义。各聚类的风险比通常与整体迟发性癫痫相似。与基础迟发性癫痫风险差异显著的聚类包括“痴呆和焦虑”（HR 5.36；95%CI 3.31-8.68）、“脑瘤”（HR 4.97；95%CI 2.89-8.56）、“ICH 和酒精滥用”（HR 2.91；95%CI 1.76-4.81）和“缺血性中风”（HR 2.83；95%CI 1.83-4.04）。与人群中肿瘤、痴呆、缺血性中风和 ICH 相关的风险比相比，这些聚类特异性风险也有所升高。与 ICH、ICH 和酒精滥用以及健康女性聚类相关的癫痫相关死因并不常见，仅限于这些聚类。
迟发性癫痫是一种独特的表型聚类的混合体，可以进行定量定义。迟发性癫痫和聚类特异性合并症特征对过早死亡的影响复杂，超过了单纯归因于癫痫和聚类定义的合并症的基础发生率。
