Kawai Kensuke, Tanaka Tatsuya, Baba Hiroshi, Bunker Mark, Ikeda Akio, Inoue Yushi, Kameyama Shigeki, Kaneko Sunao, Kato Amami, Nozawa Taneyoshi, Maruoka Eiji, Osawa Makiko, Otsuki Taisuke, Tsuji Sadatoshi, Watanabe Eiju, Yamamoto Takamichi
Jichi Medical University, Tochigi.
Yamabiko Medical Welfare Center, Kagoshima.
Epileptic Disord. 2017 Sep 1;19(3):327-338. doi: 10.1684/epd.2017.0929.
Vagus nerve stimulation (VNS) is an established option of adjunctive treatment for patients with drug-resistant epilepsy, however, evidence for long-term efficacy is still limited. Studies on clinical outcomes of VNS in Asia are also limited. We report the overall outcome of a national, prospective registry that included all patients implanted in Japan. The registry included patients of all ages with all seizure types who underwent VNS implantation for drug-resistant epilepsy in the first three years after approval of VNS in 2010. The registry excluded patients who were expected to benefit from resective surgery. Efficacy analysis was assessed based on the change in frequency of all seizure types and the rate of responders. Changes in cognitive, behavioural and social status, quality of life (QOL), antiepileptic drug (AED) use, and overall AED burden were analysed as other efficacy indices. A total of 385 patients were initially registered. Efficacy analyses included data from 362 patients. Age range at the time of VNS implantation was 12 months to 72 years; 21.5% of patients were under 12 years of age and 49.7% had prior epilepsy surgery. Follow-up rate was >90%, even at 36 months. Seizure control improved over time with median seizure reduction of 25.0%, 40.9%, 53.3%, 60.0%, and 66.2%, and responder rates of 38.9%, 46.8%, 55.8%, 57.7%, and 58.8% at three, six, 12, 24, and 36 months of VNS therapy, respectively. There were no substantial changes in other indices throughout the three years of the study, except for self/family-accessed QOL which improved over time. No new safety issues were identified. Although this was not a controlled comparative study, this prospective national registry of Japanese patients with drug-resistant epilepsy, with >90% follow-up rate, indicates long-term efficacy of VNS therapy which increased over time, over a period of up to three years. The limits of such trials, in terms of AED modifications and during follow-up and difficulties in seizure counting are also discussed.
迷走神经刺激术（VNS）是药物难治性癫痫患者辅助治疗的既定选择，然而，长期疗效的证据仍然有限。关于VNS在亚洲临床结局的研究也很有限。我们报告了一项全国性前瞻性登记研究的总体结果，该研究纳入了日本所有接受植入手术的患者。该登记研究纳入了2010年VNS获批后的头三年中所有年龄、所有发作类型且因药物难治性癫痫接受VNS植入的患者。该登记研究排除了预期可从切除性手术中获益的患者。疗效分析基于所有发作类型的发作频率变化和缓解率进行评估。认知、行为和社会状况、生活质量（QOL）、抗癫痫药物（AED）使用情况以及总体AED负担的变化作为其他疗效指标进行分析。最初共登记了385例患者。疗效分析纳入了362例患者的数据。VNS植入时的年龄范围为12个月至72岁；21.5%的患者年龄在12岁以下，49.7%的患者曾接受过癫痫手术。随访率超过90%，即使在36个月时也是如此。随着时间推移，癫痫发作得到控制，VNS治疗3个月、6个月、12个月、24个月和36个月时，癫痫发作中位数减少分别为25.0%、40.9%、53.3%、60.0%和66.2%，缓解率分别为38.9%、46.8%、55.8%、57.7%和58.8%。在研究的三年中，除了自我/家庭评估的生活质量随时间改善外，其他指标没有实质性变化。未发现新的安全问题。尽管这不是一项对照比较研究，但这项针对日本药物难治性癫痫患者的全国性前瞻性登记研究，随访率超过90%，表明VNS治疗在长达三年的时间里具有随时间增加的长期疗效。同时也讨论了此类试验在AED调整、随访期间以及癫痫发作计数方面的局限性。
