深部脑刺激可长期改善难治性癫痫

　　圣迭戈——美国癫痫学会年会上公布的一项目前仍在进行的多中心、双盲、随机研究显示，刺激双侧丘脑前核可使部分性发作频率在随访5年后降低69%(中位数)。

　　这项“刺激丘脑前核治疗癫痫”(SANTE)研究由印第安纳大学医学院综合癫痫项目主任Vicenta Salanova博士及其同事进行，共纳入110例经至少3种抗癫痫药物治疗失败的每月部分性发作或继发性全身性发作至少6次的18~65岁患者。排除IQ低于70的患者和不能完成神经心理检查或具有进行性神经系统病变的患者。

Vicenta Salanova博士

　　在为期3个月的基线期后，研究者采用立体定向技术将深部脑刺激(DBS)电极植入双侧丘脑前核。植入后1个月，患者被随机分成2组，一组接受5 V刺激，另一组不接受刺激。盲法治疗3个月后，所有患者接受刺激。长期随访在13个月时开始，刺激参数根据研究者的判断进行调整。初步分析对象为具有至少70天发作日记数据的患者。

　　盲法治疗期结束时，DBS组的中位发作频率降幅为40%，而对照组为14.5%。随着时间推移，DBS组患者的发作频率逐步降低，1年、2年和5年时相对基线时分别降低41%、56%和69%(中位数)。缓解(定义为发作频率降低≥50%)率也随时间推移而逐步增加，1年、2年和5年时的缓解率分别为43%、54%和69%。

　　研究者还发现，在整个研究期间，16%的患者至少有6个月无任何发作。未观察到非预期的不良装置反应或症状性颅内出血。1年时利物浦癫痫发作严重程度量表和癫痫患者生活质量量表-31的结果相对基线时的改善也具有统计学显著性，并且5年时的结果相对基线时仍具有显著性(P ＜ 0.001)。

　　基于该研究结果，DBS已被欧洲和加拿大批准用于治疗药物难治性部分性发作和继发性全身性发作，但尚未获得美国批准。研究者希望基于该研究结果，DBS疗法最终可获得美国批准。

　　该研究获美敦力公司资助。Salanova博士声明无相关经济利益冲突。

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　　By: DOUG BRUNK, Internal Medicine News Digital Network

　　SAN DIEGO – Bilateral stimulation of the anterior nuclei of the thalamus led to a median reduction in partial-onset seizure frequency of 69% after a follow-up period of 5 years in the ongoing multicenter, double-blind, randomized SANTE trial.

　　"We were surprised that these patients still showed improvement, despite the fact that they had failed so many other treatments, including surgery," Dr. Vicenta Salanova said during a press briefing at the annual meeting of the American Epilepsy Society. "We were happy to see that."

　　Based on SANTE (Stimulation of the Anterior Nucleus of Thalamus for Epilepsy) trial results to date, deep brain stimulation (DBS) therapy for medically refractory partial and secondarily generalized seizures has been approved in Europe and in Canada, but it remains investigational in the United States. In 2010, the SANTE trial’s sponsor, Medtronic, submitted a premarket approval application for DBS therapy in epilepsy with the Food and Drug Administration, but both parties "are still in discussions," said Dr. Salanova, professor of neurology and director of the Indiana University School of Medicine Comprehensive Epilepsy Program in Indianapolis. "We hope that, based on the results we have shown, this will eventually be approved in the United States."

　　The researchers reported on 110 participants aged 18-65 years with at least six partial or secondarily generalized seizures per month who had failed treatment with at least three antiepileptic drugs. Patients with an IQ of less than 70 and those who were unable to complete neuropsychological testing or had progressive neurologic lesions were excluded from the analysis. After a baseline period of 3 months, the researchers used a stereotactic technique to implant DBS electrodes in the anterior nuclei of the thalamus bilaterally. One month after implantation, study participants were randomized to stimulation at 5 V or to no stimulation. After 3 months of blinded treatment, all patients received stimulation. Long-term follow-up began at 13 months with stimulation parameters adjusted at the investigators’ discretion. Primary analysis was performed on patients with at least 70 days of seizure diary data.

　　Dr. Salanova reported that by the end of the blinded treatment phase, the median seizure frequency reduction was 40% in patients who underwent DBS, compared with 14.5% in controls. Over time, patients in the DBS group demonstrated stepwise improvements in the median percent reduction of seizures from baseline, to 41% at 1 year, 56% at 2 years, and 69% at 5 years. Responder rates, defined as a 50% or greater reduction in seizure frequency, also progressively improved over time to 43% at 1 year, 54% at 2 years, and 69% at 5 years.

　　The researchers also found that over the entire study period 16% of patients were seizure-free for at least 6 months. They observed no unanticipated adverse device effects or symptomatic intracranial hemorrhages. Both the Liverpool Seizure Severity Scale and Quality of Life in Epilepsy-31 inventory also showed statistically significant improvement over baseline by 1 year, which continued to be significant at 5 years (P less than .001).

　　Medtronic sponsored the study. Dr. Salanova said that she had no relevant financial conflicts to disclose.