癫痫无发作患者撤药后的长期结局及复发的危险因素分析
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摘要
目的探讨癫痫无发作患者撤药后的长期结局及影响复发的危险因素。方法本研究包含141例至少3年无发作的癫痫患者,自撤药开始随访至少3年或直到癫痫复发;根据是否复发分为无发作组和复发组;对连续变量和分类变量分别采用t检验和卡方检验。用多元回归分析复发危险因素。Kaplan-Meier生存曲线用来计算累积复发率。结果 141例患者中63例(44.7%)复发,78例(55.3%)在随访结束时仍无发作。平均复发时间是撤药后14个月,大多数复发在24个月内(81.0%);撤药后的累积复发率在第6、12、24、36、48、60个月分别为19.1%、29.8%、36.2%、42.6%、43.4%、43.4%。单因素分析显示早期3个月内药物未控制发作组复发率高于早期3个月内药物控制发作组;围产期损伤组复发率高于无围产期损伤组、需多药控制者组复发率高于单药控制组。进一步多因素回归分析发现有围产期损伤[风险比(HR)=5.000,95%置信区间(CI)=1.428～17.544]和需多药控制(HR=3.509,95%CI=1.545～8.000)是复发的独立危险因素。结论癫痫复发主要发生在开始撤药后的前24个月,撤药后3年的无发作保留率为57.4%。撤药后复发的独立危险因素是有围产期损伤史和需多药控制。
Objective To investigate the long-term outcome in seizure-free patients and the risk factors of seizure relapse following antiepileptic drug(AED)withdrawal.Methods This study included 141 patients who had been seizure-free for at least 3 years.These patients were monitored over a follow-up period of at least3 years,or until seizure relapse,after AED withdrawal.Patients were grouped into a seizure-free group and a relapse group.The Student's t test was used to compare continuous variables and the chi-squared test was used to compare categorical variables.Multiple logistic regression was used to analyze the prognostic predictors that were significantly different between groups through univariate analysis.Kaplan-Meier survival analysis was used to calculate the recurrence rates.Results Sixty-three patients(44.7%)relapsed and 78 of the 141 patients(55.3%)did not suffer a relapse at the end of the study period.The average time of relapse was 14 months after the initiation of AEDs withdrawal and majority of cases occurred within the first 24 months(81.0%).The cumulative probability of seizure recurrence following AEDs withdrawal was 19.1%,29.8%,36.2%,42.6%,43.4%,43.4% at 6,12,24,36,48,60 months,respectively.Univariate analysis showed that the likelihood of relapse was higher in patients with uncontrolled seizures beyond the first 3 months of AED therapy initiation,patients with a history of perinatal injury,and patients that had been treated with a combination of AEDs.Multiple logistic regression analysis revealed that a history of perinatal injury and AED combination therapy were independent risk factors of seizure relapse.Conclusion Epilepsy relapse occurred mainly in the first two years after the initiation of AEDs withdrawal,and seizure-free reservation rate in the third year was 57.4%.The independent risk factors of seizure relapse were a history of perinatal injury and AED combination treatment.
Objective To investigate the long-term outcome in seizure-free patients and the risk factors of seizure relapse following antiepileptic drug(AED)withdrawal.Methods This study included 141 patients who had been seizure-free for at least 3 years.These patients were monitored over a follow-up period of at least3 years,or until seizure relapse,after AED withdrawal.Patients were grouped into a seizure-free group and a relapse group.The Student's t test was used to compare continuous variables and the chi-squared test was used to compare categorical variables.Multiple logistic regression was used to analyze the prognostic predictors that were significantly different between groups through univariate analysis.Kaplan-Meier survival analysis was used to calculate the recurrence rates.Results Sixty-three patients(44.7%)relapsed and 78 of the 141 patients(55.3%)did not suffer a relapse at the end of the study period.The average time of relapse was 14 months after the initiation of AEDs withdrawal and majority of cases occurred within the first 24 months(81.0%).The cumulative probability of seizure recurrence following AEDs withdrawal was 19.1%,29.8%,36.2%,42.6%,43.4%,43.4% at 6,12,24,36,48,60 months,respectively.Univariate analysis showed that the likelihood of relapse was higher in patients with uncontrolled seizures beyond the first 3 months of AED therapy initiation,patients with a history of perinatal injury,and patients that had been treated with a combination of AEDs.Multiple logistic regression analysis revealed that a history of perinatal injury and AED combination therapy were independent risk factors of seizure relapse.Conclusion Epilepsy relapse occurred mainly in the first two years after the initiation of AEDs withdrawal,and seizure-free reservation rate in the third year was 57.4%.The independent risk factors of seizure relapse were a history of perinatal injury and AED combination treatment.
引文
[1]Duncan JS,Sander JW.Sisodiya SM and walker MC.Adult epilepsy[J].Lancet,367(9516):1087-1100.
[2]Kwan P,Brodie MJ.Early identification of refractory epilepsy[J].N Engl J Med,2000,342(5):314-319.
[3]Britton JW.Antiepileptic drug withdrawal:literature review[J].Mayo Clinic Proceedings,2002,77(12):1378-1388.
[4]Lossius ML,Hessen E,Mowinckel P,et al.Consequences of antiepileptic drug withdrawal:a randomized,double-blind study(Akershus Study)[J].Epilepsia,2008,49(3):455-463.
[5]Strozzi I,Nolan SJ,Sperling MR.,et al.Early versus late antiepileptic drug withdrawal for people with epilepsy in remission[Z].Cochrane Database Syst Rev,2015:CD001902.
[6]Lamberink HJ,Wm O,Geerts AT,et al.Individualised prediction model of seizure recurrence and long-term outcomes after withdrawal of antiepileptic drugs in seizure-free patients:a systematic review and individual participant data meta-analysis[J].Lancet Neurol,2017,16(7):523-531.
[7]Berg AT,Shinnar S.Relapse following discontinuation of antiepileptic drugs:a meta-analysis[J].Neurology,1994,44(4):601-608.
[8]Specchio LM,Beghi E.Should antiepileptic drugs be withdrawn in seizure-free patients?[J].CNS Drugs,2004,18(4):201-212.
[9]Park S,Lee DH,Kim SW and Roh YH.Prognostic analysis of patients with epilepsy according to time of relapse after withdrawal of antiepileptic drugs following four seizure-free years[J].Epilepsia,2017,58(1):60-67.
[10]Verrotti A,Trotta D,Salladini C,et al.Risk factors for recurrence of epilepsy and withdrawal of antiepileptic therapy:a practical approach[J].Ann Med,2003,35(3):207-215.
[11]Su L,Di Q,Yu N and zhang Y.Predictors for relapse after antiepileptic drug withdrawal in seizure-free patients with epilepsy[J].J Clin Neurosci,2013,20(6):790-794.
[12]Randomised Study of Antiepileptic Drug Withdrawal in Patients in Remission.Medical research council antiepileptic drug withdrawal study group[J].Lancet,1991,337(8751):1175-1180.
[13]Specchio LM,Tramacere L.La Neve A and beghi E.Discontinuing antiepileptic drugs in patients who are seizure free on monotherapy[J].J Neurol Neurosurg Psychiatry,2002,72(1):22-25.
[14]何汝茜.成人局灶性癫痫不同缓解年限撤药的复发风险比较[C]//中华医学会(Chinese Medical Association),中华医学会神经病学分会(Chinese Society of Neurology).中华医学会第十八次全国神经病学学术会议论文汇编(上),2015:1.
[15]Tang X,Yu P,Ding D,et al.Risk factors for seizure reoccurrence after withdrawal from antiepileptic drugs in individuals who have been seizure-free for over 2years[J].PLoS One,2017,12(8):e0181710.
[16]Li W,Si Y,Zou XM,et al.Prospective study on the withdrawal and reinstitution of antiepileptic drugs among seizure-free patients in west China[J].J Clin Neurosci,2014,21(6):997-1001.
[17]He RQ,Zeng QY,Zhu P,et al.Risk of seizure relapse after antiepileptic drug withdrawal in adult patients with focal epilepsy[J].Epilepsy Behav,2016,64(Pt A):233-238.
[18]Brodie MJ,Kwan P.Staged approach to epilepsy management[J].Neurology,2002,58(8Suppl 5):S2-S8.
[19]慕鹏莺.癫痫患者撤药后癫痫复发的影响因素分析[J].海南医学,2016,27(14):2351-2352.
[20]邢孔鸯,邢永前.影响癫痫患者撤药后癫痫复发的相关因素分析[J].临床医学工程,2013,20(4):446-447.
[21]Mohanraj R,Brodie MJ.Early predictors of outcome in newly diagnosed epilepsy[J].Seizure,2013,22(5):333-344.
[22]Brodie MJ,Barry SJ,Bamagous GA,et al.Patterns of treatment response in newly diagnosed epilepsy[J].Neurology,2012,78(20):1548-1554.
[23]Ashmawi A,Hosny H,Abdelalim,A.et al.The long-term prognosis of newly diagnosed epilepsy in Egypt:A retrospective cohort study from an epilepsy center in Greater Cairo[J].Seizure,2016,41:86-95.
[24]Sillanpaa M,Jalava M.Kaleva O and shinnar S.Long-term prognosis of seizures with onset in childhood[J].N Engl JMed,1998,338(24):1715-1722.
[25]Aktekin B,Dogan EA.Oguz Y and senol Y.Withdrawal of antiepileptic drugs in adult patients free of seizures for 4years:a prospective study[J].Epilepsy Behav,2006,8(3):616-619.
[26]Tang L,Xiao Z.Can electroencephalograms provide guidance for the withdrawal of antiepileptic drugs:A meta-analysis[J].Clin Neurophysiol,2017,128(2):297-302.
[2]Kwan P,Brodie MJ.Early identification of refractory epilepsy[J].N Engl J Med,2000,342(5):314-319.
[3]Britton JW.Antiepileptic drug withdrawal:literature review[J].Mayo Clinic Proceedings,2002,77(12):1378-1388.
[4]Lossius ML,Hessen E,Mowinckel P,et al.Consequences of antiepileptic drug withdrawal:a randomized,double-blind study(Akershus Study)[J].Epilepsia,2008,49(3):455-463.
[5]Strozzi I,Nolan SJ,Sperling MR.,et al.Early versus late antiepileptic drug withdrawal for people with epilepsy in remission[Z].Cochrane Database Syst Rev,2015:CD001902.
[6]Lamberink HJ,Wm O,Geerts AT,et al.Individualised prediction model of seizure recurrence and long-term outcomes after withdrawal of antiepileptic drugs in seizure-free patients:a systematic review and individual participant data meta-analysis[J].Lancet Neurol,2017,16(7):523-531.
[7]Berg AT,Shinnar S.Relapse following discontinuation of antiepileptic drugs:a meta-analysis[J].Neurology,1994,44(4):601-608.
[8]Specchio LM,Beghi E.Should antiepileptic drugs be withdrawn in seizure-free patients?[J].CNS Drugs,2004,18(4):201-212.
[9]Park S,Lee DH,Kim SW and Roh YH.Prognostic analysis of patients with epilepsy according to time of relapse after withdrawal of antiepileptic drugs following four seizure-free years[J].Epilepsia,2017,58(1):60-67.
[10]Verrotti A,Trotta D,Salladini C,et al.Risk factors for recurrence of epilepsy and withdrawal of antiepileptic therapy:a practical approach[J].Ann Med,2003,35(3):207-215.
[11]Su L,Di Q,Yu N and zhang Y.Predictors for relapse after antiepileptic drug withdrawal in seizure-free patients with epilepsy[J].J Clin Neurosci,2013,20(6):790-794.
[12]Randomised Study of Antiepileptic Drug Withdrawal in Patients in Remission.Medical research council antiepileptic drug withdrawal study group[J].Lancet,1991,337(8751):1175-1180.
[13]Specchio LM,Tramacere L.La Neve A and beghi E.Discontinuing antiepileptic drugs in patients who are seizure free on monotherapy[J].J Neurol Neurosurg Psychiatry,2002,72(1):22-25.
[14]何汝茜.成人局灶性癫痫不同缓解年限撤药的复发风险比较[C]//中华医学会(Chinese Medical Association),中华医学会神经病学分会(Chinese Society of Neurology).中华医学会第十八次全国神经病学学术会议论文汇编(上),2015:1.
[15]Tang X,Yu P,Ding D,et al.Risk factors for seizure reoccurrence after withdrawal from antiepileptic drugs in individuals who have been seizure-free for over 2years[J].PLoS One,2017,12(8):e0181710.
[16]Li W,Si Y,Zou XM,et al.Prospective study on the withdrawal and reinstitution of antiepileptic drugs among seizure-free patients in west China[J].J Clin Neurosci,2014,21(6):997-1001.
[17]He RQ,Zeng QY,Zhu P,et al.Risk of seizure relapse after antiepileptic drug withdrawal in adult patients with focal epilepsy[J].Epilepsy Behav,2016,64(Pt A):233-238.
[18]Brodie MJ,Kwan P.Staged approach to epilepsy management[J].Neurology,2002,58(8Suppl 5):S2-S8.
[19]慕鹏莺.癫痫患者撤药后癫痫复发的影响因素分析[J].海南医学,2016,27(14):2351-2352.
[20]邢孔鸯,邢永前.影响癫痫患者撤药后癫痫复发的相关因素分析[J].临床医学工程,2013,20(4):446-447.
[21]Mohanraj R,Brodie MJ.Early predictors of outcome in newly diagnosed epilepsy[J].Seizure,2013,22(5):333-344.
[22]Brodie MJ,Barry SJ,Bamagous GA,et al.Patterns of treatment response in newly diagnosed epilepsy[J].Neurology,2012,78(20):1548-1554.
[23]Ashmawi A,Hosny H,Abdelalim,A.et al.The long-term prognosis of newly diagnosed epilepsy in Egypt:A retrospective cohort study from an epilepsy center in Greater Cairo[J].Seizure,2016,41:86-95.
[24]Sillanpaa M,Jalava M.Kaleva O and shinnar S.Long-term prognosis of seizures with onset in childhood[J].N Engl JMed,1998,338(24):1715-1722.
[25]Aktekin B,Dogan EA.Oguz Y and senol Y.Withdrawal of antiepileptic drugs in adult patients free of seizures for 4years:a prospective study[J].Epilepsy Behav,2006,8(3):616-619.
[26]Tang L,Xiao Z.Can electroencephalograms provide guidance for the withdrawal of antiepileptic drugs:A meta-analysis[J].Clin Neurophysiol,2017,128(2):297-302.
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