撤药后复发癫痫患者的预后及其影响因素研究

Prognosis and its influencing factors of patients with seizure recurrence after anti-epileptic drug withdrawal

目的探讨撤药后复发癫痫患者的二次复发和预后不良的影响因素。方法收集2009年12月至2018年8月就诊于南京医科大学附属脑科医院癫痫专科门诊确诊为癫痫、达至少3年无发作且经规范化撤药后复发的患者,自撤药后初次复发开始至少随访18个月,前瞻性观察患者的二次复发和预后情况。采用卡普兰-迈耶法对撤药后复发患者二次复发和至少1年无发作的时间进行生存分析;至随访终点,根据撤药后复发患者是否达至少1年无发作,将其分为预后好组和预后差组;采用多因素分析方法分析影响患者二次复发和预后不良的危险因素。结果共收集56例撤药后复发的癫痫患者。自撤药后复发开始平均随访46.23个月(18~120个月),二次复发患者21例(37.5%)。其中撤药后初次复发未立即用药患者的二次复发风险高于立即重建药物治疗患者[9/16比30.0%(12/40)],但两者差异无统计学意义(χ^(2)=2.220,P=0.071)。单因素分析结果显示:局灶性发作、缓解前发作频率>1次/月、撤药前多药联合治疗与二次复发相关;多因素分析结果显示:多药联合治疗是撤药后复发患者二次复发的独立危险因素(HR=3.383,95%CI 1.257~9.105)。在56例撤药后复发的癫痫患者中,47例患者(83.9%)达至少1年无发作;在随访时间≥3年的33例患者中,26例(78.8%)达至少2年无发作。在撤药后初次复发后立即用药的40例患者中,35例预后好(87.5%),在初次复发后未立即用药16例患者中,12例预后好,两者差异也无统计学意义(χ^(2)=2.333,P=0.258)。单因素分析结果显示,初始治疗前癫痫病程>6个月、缓解前发作频率>1次/月、症状性癫痫、多种药物联合治疗与撤药后复发患者的不良预后相关;多因素分析未显示上述因素是该类患者预后不良的独立危险因素。结论首次撤药后复发的癫痫患者总体预后较好,2/3撤药后复发的患者不会二次复发。撤药前多种药物联合治疗是撤药后复发患者二次复发的独立危险因素。

Objective To explore the seizure recurrence and prognosis of epilepsy in relapse after anti-epileptic drugs(AEDs)withdrawal,and the influencing factors for these conditions.Methods From December 2009 to August 2018,patients from the Affiliated Brain Hospital of Nanjing Medical University who relapsed after AEDs withdrawal were collected and followed up for at least 18 months.The seizure recurrence and prognosis of these patients were prospectively observed.The Kaplan-Meier method was used for survival analysis.The associated risk factors of the second relapse in the enrolled patients were analyzed by multivariate Cox analysis.The included patients were divided into good prognosis group and poor prognosis group according to whether they had achieved seizure freedom for at least one year after the first relapse.A multivariate Cox regression model was used to analyze the independent risk factors affecting their prognosis.Results A total of 56 patients with epilepsy in relapse after AEDS withdrawal were collected.The average follow-up period was 46.23 months(18-120 months)from the initial time of seizure recurrence,and 21 patients(37.5%)had the second seizure recurrence.The relapsing risk in patients who continued to be observed without adding AEDs was higher than those who were treated immediately with drugs[9/16vs 30.0%(12/40)],but without statistically significant difference(χ^(2)=2.220,P=0.071).The results of univariate analysis showed that focal seizures,seizure frequency more than once per month before remission and poly-drug therapy before AEDs withdrawal were associated with high risk of the second relapse.Poly-drug therapy was an independent risk factor for the second relapse by multivariate Cox analysis(HR=3.383,95%CI 1.257-9.105).Of the 56 patients with epilepsy in relapse after AEDs withdrawal,47 patients(83.9%)had a good prognosis without seizure for at least one year,and of 33 patients who were followed up for three years or more,26(78.8%)had no seizure for at least two years.Between the group retreated immediately after the first recurrence and the group without immediate treatment[87.5%(35/40)vs 12/16],there were no statistically significant differences on the proportions of good prognosis(χ^(2)=2.333,P=0.258).Univariate analysis showed that the course of epilepsy>6 months before initial treatment,the frequency of seizures>1/month before remission,symptomatic epilepsy and poly-drug therapy were associated with the poor prognosis.However,none of independent risk factors was found for the poor prognosis through the multivariate analysis.Conclusions The prognosis of patients with epilepsy in relapse after AEDs withdrawal is well,and about 2/3 patients with epilepsy in relapse after AEDs withdrawal have no more seizure recurrences.The poly-drug therapy before AEDs withdrawal may be an independent risk factor for the second seizure relapse.