Homerton University Hospital, NHS Foundation Trust, London, UK.
Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.
Cochrane Database Syst Rev. 2023 Jan 23;1(1):CD013847. doi: 10.1002/14651858.CD013847.pub2.
BACKGROUND: Epilepsy is clinically defined as two or more unprovoked epileptic seizures more than 24 hours apart. Given that, a diagnosis of epilepsy can be associated with significant morbidity and mortality, it is imperative that clinicians (and people with seizures and their relatives) have access to accurate and reliable prognostic estimates, to guide clinical practice on the risks of developing further unprovoked seizures (and by definition, a diagnosis of epilepsy) following single unprovoked epileptic seizure. OBJECTIVES: 1. To provide an accurate estimate of the proportion of individuals going on to have further unprovoked seizures at subsequent time points following a single unprovoked epileptic seizure (or cluster of epileptic seizures within a 24-hour period, or a first episode of status epilepticus), of any seizure type (overall prognosis). 2. To evaluate the mortality rate following a first unprovoked epileptic seizure. SEARCH METHODS: We searched the following databases on 19 September 2019 and again on 30 March 2021, with no language restrictions. The Cochrane Register of Studies (CRS Web), MEDLINE Ovid (1946 to March 29, 2021), SCOPUS (1823 onwards), ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). CRS Web includes randomized or quasi-randomized, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups including Epilepsy. In MEDLINE (Ovid) the coverage end date always lags a few days behind the search date. SELECTION CRITERIA: We included studies, both retrospective and prospective, of all age groups (except those in the neonatal period (< 1 month of age)), of people with a single unprovoked seizure, followed up for a minimum of six months, with no upper limit of follow-up, with the study end point being seizure recurrence, death, or loss to follow-up. To be included, studies must have included at least 30 participants. We excluded studies that involved people with seizures that occur as a result of an acute precipitant or provoking factor, or in close temporal proximity to an acute neurological insult, since these are not considered epileptic in aetiology (acute symptomatic seizures). We also excluded people with situational seizures, such as febrile convulsions. DATA COLLECTION AND ANALYSIS: Two review authors conducted the initial screening of titles and abstracts identified through the electronic searches, and removed non-relevant articles. We obtained the full-text articles of all remaining potentially relevant studies, or those whose relevance could not be determined from the abstract alone and two authors independently assessed for eligibility. All disagreements were resolved through discussion with no need to defer to a third review author. We extracted data from included studies using a data extraction form based on the checklist for critical appraisal and data extraction for systematicreviews of prediction modelling studies (CHARMS). Two review authors then appraised the included studies, using a standardised approach based on the quality in prognostic studies (QUIPS) tool, which was adapted for overall prognosis (seizure recurrence). We conducted a meta-analysis using Review Manager 2014, with a random-effects generic inverse variance meta-analysis model, which accounted for any between-study heterogeneity in the prognostic effect. We then summarised the meta-analysis by the pooled estimate (the average prognostic factor effect), its 95% confidence interval (CI), the estimates of I² and Tau² (heterogeneity), and a 95% prediction interval for the prognostic effect in a single population at three various time points, 6 months, 12 months and 24 months. Subgroup analysis was performed according to the ages of the cohorts included; studies involving all ages, studies that recruited adult only and those that were purely paediatric. MAIN RESULTS: Fifty-eight studies (involving 54 cohorts), with a total of 12,160 participants (median 147, range 31 to 1443), met the inclusion criteria for the review. Of the 58 studies, 26 studies were paediatric studies, 16 were adult and the remaining 16 studies were a combination of paediatric and adult populations. Most included studies had a cohort study design with two case-control studies and one nested case-control study. Thirty-two studies (29 cohorts) reported a prospective longitudinal design whilst 15 studies had a retrospective design whilst the remaining studies were randomised controlled trials. Nine of the studies included presented mortality data following a first unprovoked seizure. For a mortality study to be included, a proportional mortality ratio (PMR) or a standardised mortality ratio (SMR) had to be given at a specific time point following a first unprovoked seizure. To be included in the meta-analysis a study had to present clear seizure recurrence data at 6 months, 12 months or 24 months. Forty-six studies were included in the meta-analysis, of which 23 were paediatric, 13 were adult, and 10 were a combination of paediatric and adult populations. A meta-analysis was performed at three time points; six months, one year and two years for all ages combined, paediatric and adult studies, respectively. We found an estimated overall seizure recurrence of all included studies at six months of 27% (95% CI 24% to 31%), 36% (95% CI 33% to 40%) at one year and 43% (95% CI 37% to 44%) at two years, with slightly lower estimates for adult subgroup analysis and slightly higher estimates for paediatric subgroup analysis. It was not possible to provide a summary estimate of the risk of seizure recurrence beyond these time points as most of the included studies were of short follow-up and too few studies presented recurrence rates at a single time point beyond two years. The evidence presented was found to be of moderate certainty. AUTHORS' CONCLUSIONS: Despite the limitations of the data (moderate-certainty of evidence), mainly relating to clinical and methodological heterogeneity we have provided summary estimates for the likely risk of seizure recurrence at six months, one year and two years for both children and adults. This provides information that is likely to be useful for the clinician counselling patients (or their parents) on the probable risk of further seizures in the short-term whilst acknowledging the paucity of long-term recurrence data, particularly beyond 10 years.
背景:癫痫在临床上被定义为两次或两次以上无诱因的癫痫发作,间隔超过 24 小时。鉴于此,癫痫的诊断可能与显著的发病率和死亡率相关,因此临床医生(以及有癫痫发作和亲属的人)必须能够获得准确和可靠的预后估计,以指导临床实践,了解在单次无诱因癫痫发作后进一步发生无诱因癫痫发作(并由此定义为癫痫)的风险。
目的:1. 提供在单次无诱因癫痫发作(或 24 小时内的癫痫发作群,或首次癫痫持续状态)后,任何类型癫痫发作(总体预后)的个体在随后的时间点进一步发生无诱因癫痫发作的比例的准确估计。2. 评估首次无诱因癫痫发作后的死亡率。
检索方法:我们于 2019 年 9 月 19 日和 2021 年 3 月 30 日在以下数据库中进行了搜索,没有语言限制。Cochrane 对照试验注册中心(CRS Web)、MEDLINE Ovid(1946 年至 2021 年 3 月 29 日)、SCOPUS(1823 年起)、ClinicalTrials.gov、世界卫生组织(WHO)国际临床试验注册平台(ICTRP)。CRS Web 包括来自 PubMed、Embase、ClinicalTrials.gov、世界卫生组织国际临床试验注册平台(ICTRP)、Cochrane 中心对照试验注册(CENTRAL)和包括癫痫在内的 Cochrane 综述组的专门登记册的随机或准随机对照试验。在 MEDLINE(Ovid)中,覆盖结束日期总是滞后于搜索日期几天。
选择标准:我们纳入了所有年龄段(新生儿期(<1 个月)除外)的研究,这些研究包括单次无诱因发作的人群,随访时间至少 6 个月,无随访上限,研究终点为发作复发、死亡或失访。为了被纳入,研究必须至少包含 30 名参与者。我们排除了那些因急性诱发因素或急性神经损伤而发生的癫痫发作的研究,因为这些在病因上不属于癫痫(急性症状性癫痫发作)。我们还排除了情境性癫痫发作(如热性惊厥)的患者。
数据收集和分析:两名综述作者对通过电子搜索确定的标题和摘要进行了初步筛选,并删除了不相关的文章。我们获得了所有剩余的潜在相关研究的全文文章,或那些仅从摘要无法确定其相关性的文章,并由两名作者独立评估其纳入性。所有分歧都通过讨论解决,无需提交给第三位综述作者。我们使用基于预测模型研究的关键评估和数据提取清单(CHARMS)的数据集提取表,从纳入的研究中提取数据。然后,两名综述作者使用基于质量预后研究(QUIPS)工具的标准化方法,根据纳入研究的预后效果进行评估,该方法适用于总体预后(癫痫发作复发)。我们使用 Review Manager 2014 进行了荟萃分析,采用随机效应通用逆方差荟萃分析模型,该模型考虑了研究之间预后效果的任何异质性。然后,我们根据三个不同的时间点(6 个月、12 个月和 24 个月),使用单个人群的汇总估计值(平均预后因素效果)、其 95%置信区间(CI)、I²和 Tau²(异质性)以及 95%预测区间,总结了荟萃分析的结果。根据纳入的队列年龄进行了亚组分析;包括所有年龄的队列、仅招募成年人的队列和完全是儿科的队列。
主要结果:58 项研究(涉及 54 个队列),共 12160 名参与者(中位数 147,范围 31 至 1443)符合综述纳入标准。58 项研究中,26 项为儿科研究,16 项为成人研究,其余 16 项为儿科和成人混合人群研究。大多数纳入的研究为队列研究设计,其中 29 项为病例对照研究,1 项为嵌套病例对照研究。32 项研究(29 个队列)报告了前瞻性纵向设计,15 项研究为回顾性设计,其余研究为随机对照试验。9 项研究报告了首次无诱因癫痫发作后的死亡率。为了纳入荟萃分析,一项研究必须在特定时间点给出比例死亡率(PMR)或标准化死亡率(SMR)。为了纳入荟萃分析,研究必须在 6 个月、12 个月或 24 个月时明确报告癫痫发作复发数据。46 项研究被纳入荟萃分析,其中 23 项为儿科研究,13 项为成人研究,10 项为儿科和成人混合研究。对所有年龄、儿科和成人研究分别进行了 6 个月、1 年和 2 年的荟萃分析。我们发现所有纳入研究在 6 个月时的总体癫痫发作复发率为 27%(95%CI 24%至 31%),1 年时为 36%(95%CI 33%至 40%),2 年时为 43%(95%CI 37%至 44%),成人亚组分析的估计值略低,儿科亚组分析的估计值略高。由于大多数纳入的研究随访时间较短,而且很少有研究在两年后报告复发率,因此无法提供超过这些时间点的复发风险的汇总估计。目前提供的证据被认为是中等确定性的。
作者结论:尽管数据存在局限性(证据的中等确定性),主要与临床和方法学异质性有关,但我们已经为儿童和成人提供了 6 个月、1 年和 2 年时癫痫复发风险的汇总估计值。这提供了在短期内可能有用的信息,以便临床医生在向患者(或其父母)提供咨询时,了解在短期内发生进一步癫痫发作的可能性,同时认识到长期复发数据的缺乏,特别是超过 10 年的复发数据。
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