Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial.
Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial.
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DOI：
10.1001/jama.2012.220
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发表时间：
2012-03-07
期刊：
影响因子：
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通讯作者：
Early Randomized Surgical Epilepsy Trial (ERSET) Study Group
中科院分区：
文献类型：
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作者：
Engel J Jr;McDermott MP;Wiebe S;Langfitt JT;Stern JM;Dewar S;Sperling MR;Gardiner I;Erba G;Fried I;Jacobs M;Vinters HV;Mintzer S;Kieburtz K;Early Randomized Surgical Epilepsy Trial (ERSET) Study Group
尽管有成功的报道，但手术治疗耐药癫痫通常被视为最后的手段。患者通常在癫痫发作20年后进行手术，但往往为时已晚，无法避免严重的残疾和过早死亡。我们试图确定在2例抗癫痫药物（AED）试验失败后立即手术是否优于继续医疗管理在控制癫痫发作和改善生活质量（QOL）方面。早期随机手术癫痫试验（ERSET）是一项在美国16个癫痫手术中心进行的多中心、对照、平行组临床试验。38名参与者（18名男性和20名女性，年龄≥12岁）在接受了2种名牌抗癫痫药的充分试验后，患有内侧颞叶癫痫（MTLE）和致残性癫痫发作的时间不超过连续2年。子宫前颞叶切除术（AMTR）的资格是基于标准化的术前评估方案。参与者被随机分配到继续AED治疗组或AMTR 2003-2007组，观察2年。原计划入组人数为200人，但由于累积缓慢，试验提前终止。接受持续AED治疗（n=23）或标准化AMTR加AED治疗（n= 15）。在医疗组中，7名参与者在随访结束前接受了AMTR，而在手术组中，1名参与者从未接受过手术。主要结局变量为随访第2年无致残性癫痫发作。次要结局变量为与健康相关的生活质量（主要通过癫痫患者生活质量89 [QOLIE-89]总t评分的2年变化来衡量）、认知功能和社会适应。在随访的第2年中，内科组23名患者中0名无癫痫发作，手术组15名患者中11名无癫痫发作（优势比=∞;95% CI， 11.8至∞；P <.001）。意向治疗分析中，手术组QOLIE-89总t评分的平均改善高于内科组，但差异无统计学意义（12.6 vs 4.0分；治疗效果= 8.5;95% CI, - 1.0 ~ 18.1; P = 0.08）。排除内科组患者术后获得的资料后，手术对生活质量的影响显著（12.8 vs 2.8分；治疗效果=9.9;95% CI, 2.2 ~ 17.7; P = 0.01）。4名参与者（36%）在手术后出现记忆衰退（使用Rey听觉语言学习测试评估），与文献中看到的发生率一致；但样本太小，无法得出关于治疗组认知结果差异的明确结论。不良事件包括一名接受手术的参与者因磁共振成像确定的术后卒中而出现一过性神经功能缺损，以及3例药物组的癫痫持续状态。在新发难治性致残性MTLE患者中，切除手术加AED治疗在随访第2年期间癫痫发作的概率低于单独AED治疗。鉴于试验过早终止，对结果的解释应适当谨慎。
Despite reported success, surgery for pharmacoresistant seizures is often seen as a last resort. Patients are typically referred for surgery after 20 years of seizures, often too late to avoid significant disability and premature death. We sought to determine whether surgery soon after failure of 2 antiepileptic drug (AED) trials is superior to continued medical management in controlling seizures and improving quality of life (QOL). The Early Randomized Surgical Epilepsy Trial (ERSET) is a multicenter, controlled, parallel-group clinical trial performed at 16 US epilepsy surgery centers. The 38 participants (18 men and 20 women; aged ≥ 12 years) had mesial temporal lobe epilepsy (MTLE) and disabling seizues for no more than 2 consecutive years following adequate trials of 2 brand-name AEDs. Eligibility for anteromesial temporal resection (AMTR) was based on a standardized presurgical evaluation protocol. Participants were randomized to continued AED treatment or AMTR 2003–2007, and observed for 2 years. Planned enrollment was 200, but the trial was halted prematurely due to slow accrual. Receipt of continued AED treatment (n=23) or a standardized AMTR plus AED treatment (n = 15). In the medical group, 7 participants underwent AMTR prior to the end of follow-up and 1 participant in the surgical group never received surgery. The primary outcome variable was freedom from disabling seizures during year 2 of follow-up. Secondary outcome variables were health-related QOL (measured primarily by the 2-year change in the Quality of Life in Epilepsy 89 [QOLIE-89] overall T-score), cognitive function, and social adaptation. Zero of 23 participants in the medical group and 11 of 15 in the surgical group were seizure free during year 2 of follow-up (odds ratio=∞; 95% CI, 11.8 to ∞;P <.001). In an intention-to-treat analysis, the mean improvement in QOLIE-89 overall T-score was higher in the surgical group than in the medical group but this difference was not statistically significant (12.6 vs 4.0 points; treatment effect = 8.5; 95% CI, −1.0 to 18.1; P =.08). When data obtained after surgery from participants in the medical group were excluded, the effect of surgery on QOL was significant (12.8 vs 2.8 points; treatment effect=9.9; 95% CI, 2.2 to 17.7; P =.01). Memory decline (assessed using the Rey Auditory Verbal Learning Test) occurred in 4 participants (36%) after surgery, consistent with rates seen in the literature; but the sample was too small to permit definitive conclusions about treatment group differences in cognitive outcomes. Adverse events included a transient neurologic deficit attributed to a magnetic resonance imaging–identified postoperative stroke in a participant who had surgery and 3 cases of status epilepticus in the medical group. Among patients with newly intractable disabling MTLE, resective surgery plus AED treatment resulted in a lower probability of seizures during year 2 of follow-up than continued AED treatment alone. Given the premature termination of the trial, the results should be interpreted with appropriate caution.