神经电刺激治疗慢性头面部疼痛：综述（十八）

 英语晨读 ·

山东省立医院疼痛科英语晨读已经坚持10余年的时间了，每天交班前15分钟都会精选一篇英文文献进行阅读和翻译。一是可以保持工作后的英语阅读习惯，二是可以学习前沿的疼痛相关知识。我们会将晨读内容与大家分享，助力疼痛学习。

本次文献选自Antony AB,  Mazzola AJ,  Dhaliwal GS, et al. Neurostimulation for the Treatment of Chronic Head and Facial Pain: A Literature Review[J]. Pain Physician, 2019, 22(5):447-477. 本次学习由陈阳住院医师主讲。

The GON has been a promising target for PNS for not only occipital neuralgia, but a variety of other painful conditions of the head and neck, including both primary and secondary headache disorders. Contrary to other PNS targets for head and facial pain, there have been prospective, RCTs reported on the use of ONS. The ONSTIM trial was a prospective, multicenter, singleblinded, feasibility RCT sponsored by Medtronic Inc. using ONS for chronic intractable migraine. Patients were randomized into adjustable stimulation (n = 28), preset stimulation (n = 16), and medical management (n = 17) groups. At 3 months after implantation, 39% of patients in the adjustable stimulation group showed a reduction in headache days per month or a > 3 point reduction in pain scores. Of note, 24% of implanted patients were noted to have lead migration in the study. This led the authors to conclude that although the data collected were promising for the treatment of migraines using ONS, more studies are needed in this area.

枕大神经作为PNS的靶点，不仅治疗枕神经痛，而且治疗包括原发性和继发性头痛在内的多种其他头颈部疼痛状况。与其他治疗头面部疼痛PNS的靶点不同， 对于ONS有前瞻性RCT研究。 ONSTIM试验是由Medtronic Inc.赞助的前瞻性、多中心、单盲、可行性RCT，使用ONS治疗慢性顽固性偏头痛。将患者随机分为可调刺激组（n = 28），预设刺激组（n = 16）和药物治疗组（n = 17）。植入后3个月，可调刺激组的患者中有39％的患者每月头痛天数减少或疼痛评分降低了> 3。值得注意的是，研究中有24％的植入患者发生电极移位。这使作者得出结论，尽管收集到的数据对于使用ONS治疗偏头痛很有前途，但在这一领域还需要更多的研究。

Another prospective RCT using ONS was sponsored by St. Jude Medical. This multicenter, doubleblinded, controlled study used ONS trials followed by both active stimulation implants and sham implants in 157 patients with 125 meeting the criteria for intractable CM. Approximately two-thirds of the patients were randomized into the active stimulation implanted group by design. The study failed to show a significant difference in the sham versus active stimulation group in the primary endpoint, a reduction in daily mean Visual Analog Scale (VAS) pain scores by 50% at 3 months. However, there was a significant difference shown between the 2 groups in patients reporting a 30% reduction of daily VAS scores. Dodick et al followed this by reporting one-year data in the study. A significant reduction in number of headache days and headache disability indices were reported along with encouraging reductions in headache intensity. Unfortunately, a high number of patients (70%) suffered a postoperative adverse event, nearly half (40%) of which required surgical intervention. The authors concluded that although results support the 12-month efficacy of PNS of the occipital nerves for headache pain and disability, more emphasis on adverse event mitigation is needed in future research. A recent review and meta-analysis of ONS for CM included several additional older RCTs and 7 case series. It concluded that although efficacy for ONS in migraine over sham has been established, “the average effect size is modest” and “further measures to reduce the risk of adverse events and revision surgery are needed.”

St. Jude Medical赞助了另一种使用ONS的前瞻性RCT。这项多中心、双盲、对照研究在ONS测试后，对157例符合难治性CM标准的患者进行了活动刺激植入和假刺激植入。通过设计将大约三分之二的患者随机分为活动刺激植入组。该研究发现假手术组与主动刺激组在主要终点方面不存在显着差异，即在3个月时每日视觉模拟量表（VAS）疼痛评分降低了50％。但是，VAS降低30％时两组之间存在显着差异。 Dodick等人随后报告了这项研究中的一年数据。据报道，头痛天数和头痛失能指数显著减少，同时头痛程度也得到了很大的缓解。不幸的是，大量患者（70％）出现术后不良反应，其中近一半（40％）需要手术干预。作者得出的结论是，尽管研究结果支持枕神经PNS治疗头痛和失能的1年疗效，但在未来的研究中仍需要更加重视解决不良事件。近期针对CM的ONS的综述和荟萃分析检索了其他一些较旧的RCT和7个病例系列。其得出结论，尽管与假手术组相比已经明确了ONS在偏头痛中的疗效，但“平均效果适中”，并且“需要采取进一步措施以减少不良事件和翻修手术的风险。”

Focusing on CHs, Burns et al analyzed 8 patients who had been implanted bilaterally with ONS for control of medically intractable chronic CH. The results of this open-label, case series were promising at a median follow-up period of 20 months: 2 patients noted a substantial improvement, 3 patients showed moderate improvement, and 1 reported mild improvement. Of note the first patient was implanted on ipsilateral side to where 95% of the attacks were located, after stimulation the geographic nature of the attacks changed, and thus bilateral stimulators was placed. From then on, each patient was implanted bilaterally. During device malfunctions, including battery depletion, the patients reported a return of symptoms. A total of 6 out of the 8 patients would recommend the procedure. Overall, these cases suggest ONS for CH is promising. Of all the neuromodulation studies involving PNS for face or head pain, the ONS currently has the greatest level of supporting evidence for treatments including migraine, CH, and occipital neuralgia.

Burns等人分析了8例双侧植入ONS的患者，以控制顽固性慢性CH。这个开放标签病例系列的结果在中位随访期20个月中很有希望：2例患者有明显改善，3例患者中度改善，1例患者轻度改善。值得注意的是，第一名患者先植入电极至95％发作所在的同侧，在刺激后，发作的部位发生了变化，因此放置了双侧刺激器。从那时起，每位患者都进行了双边植入。当设备故障（包括电池耗尽）时，患者的症状复现。8例患者中总共6例适合该方法。总体而言，这些案例表明用于CH的ONS是有前途的。在涉及PNS的头面部疼痛的所有神经调节研究中，ONS目前具有最高等级证据支持其治疗包括偏头痛、CH和枕神经痛在内的疾病。