偏头痛药物治疗失败时神经刺激可能有效

洛杉矶——美国头痛学会年会上报告的一项针对偏头痛药物治疗无应答患者的随机双盲试验显示，枕部神经刺激可使慢性偏头痛缓解。

该研究中，费城杰佛逊头痛中心的研究者纳入125例每月至少15天有头痛发作、至少3种预防性药物治疗失败并发生中度头痛相关障碍的慢性、难治性偏头痛患者。其疼痛必须在10 cm视觉模拟量表中标注在6 cm以上，且疼痛局限于头后部或起源于颈部区域。不要求患者既往对枕部神经阻滞有应答，Silberstein博士解释：“无证据支持枕部神经阻滞可预测对神经刺激的应答。”纳入过度使用药物的患者，但不包括使用阿片类药物的患者。对所有患者置入St. Jude Medical的神经刺激系统，并随机分配至神经刺激组(n=88)或安慰剂组(n=37)。

Stephen Silberstein博士

结果显示，12周时，神经刺激组约有70%的患者报告良好或中度疼痛缓解，而对照组仅有20%(P=0.001)。接受活性神经刺激治疗的患者达到视觉模拟量表评估的平均每日疼痛强度降低10%、20%或30%的比例较高(P值均＜0.05)。“在这一特定试验中也观察到40%、50%和 60%的差异，虽然没有统计学意义，但要注意这是一个3种治疗失败的致残性偏头痛人群。”神经刺激组平均每月头痛发作天数的减少幅度也较大(分别为7.0天和2.7天；P=0.03)，并且达到头痛发作天数减少10%、20%、30%和40%的患者比例更高(P值均＜0.05)。关于头痛相关障碍，神经刺激组患者MIDAS(偏头痛致残性评估)评分(分别降低73分和27分；P=0.001)和Zung疼痛与苦恼量表评分的降低幅度(分别降低15分和6分，P=0.001)也较对照组更大。

神经刺激组和安慰剂组的总体不良事件发生率分别约为61%和49%。最主要的硬件相关不良事件为导线移位，并因此导致15%的不良事件，并且在神经刺激组发生率较高。“如果安装了活性刺激装置后疼痛缓解，然后疼痛缓解作用却消失了，就很容易确定发生了导线移位。”Silberstein博士补充说，随着手术技术的改进，导线移位的问题已越来越少。最主要的生物学不良事件为植入脉搏发生器或导线部位持续疼痛和(或)麻木，并因此导致22%的不良事件。

研究者总结认为，对于所有其他治疗均无效的慢性偏头痛患者，枕部神经的外周神经刺激治疗可能有效。该研究为难治性慢性偏头痛的外周神经刺激治疗的安全性和疗效提供了很强的支持性证据。

该研究由St. Jude Medical公司神经调控部门资助。Silberstein博士披露接受了该部门提供的咨询费/酬金和研究支持。

爱思唯尔  版权所有

By: SUSAN LONDON, Clinical Neurology News Digital Network

LOS ANGELES – Occipital nerve stimulation provided relief from chronic migraine in a randomized, double-blind trial of patients who had not responded to currently available pharmacologic therapies.

The 12-week trial of 125 patients found that patients who received active neurostimulation were about four times more likely to rate their pain relief as excellent or fair than were those who received sham neurostimulation. The actively-stimulated patients also had more than double the reduction in number of days with headache each month.

"This is the first large-scale study of peripheral nerve stimulation for intractable chronic migraine that showed a significant reduction in pain, number of headache-days, and migraine-related disability," said lead investigator Dr. Stephen D. Silberstein of the Jefferson Headache Center in Philadelphia.

"These results suggest that patients who have exhausted all treatment options may benefit from peripheral nerve stimulation of the occipital nerves," he added. "These results provide the strongest evidence to date to support the safety and efficacy of peripheral nerve stimulation for intractable chronic migraine."

Session attendee Dr. Peter Goadsby of the University of California, San Francisco, questioned whether the trial was truly blinded, given the challenge of concealing group assignment when using neurostimulation. "It is very difficult. ... Much of the blinding in these studies is compromised," he said at the annual meeting of the American Headache Society. "I think it’s not fair to say this is the strongest evidence for peripheral nerve, occipital nerve stimulation. I think it’s another piece of evidence, but I don’t think that we have hit a home run here. ... I don’t think this is prime time yet."

"I’m not disagreeing with you," Dr. Silberstein replied. "I am saying of all the trials, in the subset of patients we defined as intractable chronic migraine, this is the best evidence so far. ... How do you blind brain stimulation trials? That’s a fundamental problem," he acknowledged, noting that patients in the trial were told that they were receiving neurostimulation with different parameters. "It’s very difficult and very complicated to control with any active stimulation device. We tried the best we could."

In the trial, the investigators enrolled patients with chronic, intractable migraines who had headache at least 15 days a month, had experienced a failure of at least three preventive medications, and had moderate headache-related disability. Their pain had to be at least 6 cm out of 10 cm on a visual analog scale and localized to the posterior head or originating from the cervical region.

Patients were not required to have responded previously to an occipital nerve block, Dr. Silberstein noted, explaining that "there is no evidence at all that occipital nerve block is predictive of the response to stimulation." Patients who overused medication were included, but those taking opioids were not.

All patients underwent implantation of St. Jude Medical’s neurostimulation system and were randomized to the neurostimulation group (n = 88) or the control group (n = 37).

Results showed that about 70% of patients in the neurostimulation group reported excellent or fair pain relief at 12 weeks, compared with only 20% of their counterparts in the control group (P = .001).

Patients who received active neurostimulation were also more likely to achieve a reduction in mean daily pain intensity on the visual analogue scale of 10%, 20%, or 30% (P less than .05 for each). "Looking at 40%, 50%, and 60% differences in this particular trial, they were not statistically significant differences, but again, remember, this was a disabling migraine population that had failed three therapies," Dr. Silberstein commented.

The neurostimulation group also had a greater mean reduction in monthly number of headache-days (7.0 vs. 2.7 days; P = .03) and were more likely to have a 10%, 20%, 30%, and 40% reduction in the number (P less than .05 for each).

In terms of headache-related disability, patients in the neurostimulation group also had a greater reduction in MIDAS (Migraine Disability Assessment) scores (a drop of 73 points vs. a drop of 27 points; P = .001) and in Zung Pain and Distress Scale scores (by 15 vs. 6 points, P = .001).

The overall rate of adverse events was about 61% in the neurostimulation group and 49% in the control group.

The leading hardware-related adverse event was lead migration, accounting for 15% of all events, with a higher rate in the neurostimulation group. "If you have a device in and it’s actively stimulating and you are getting pain relief, and then the pain relief ceases, it’s easier to identify the fact that you have had lead migration," Dr. Silberstein explained, adding that lead migration has become much less problematic as surgical techniques have improved.

The leading biological adverse event was persistent pain and/or numbness at the implantable pulse generator or lead site, which accounted for 22% of all events.

Dr. Silberstein disclosed that he receives consulting fees/honoraria and research support from St. Jude Medical Neuromodulation Division, which funded the trial.