LAS VEGAS—In cluster headache, four neuromodulation techniques have been tested—deep brain stimulation (DBS), vagal nerve stimulation (VNS), sphenopalatine ganglion (SPG) stimulation, and occipital nerve stimulation (ONS). At the 17th Annual Meeting of the North American Neuromodulation Society, Stewart Tepper, MD, assessed the available evidence for each treatment modality.
Deep Brain Stimulation
“The idea of doing DBS for cluster headache was generated by the severity of what we saw in our patients,” said Dr. Tepper, who is Director of Research for the Neurological Center for Pain at the Cleveland Clinic. Early research was promising, but revealed drawbacks. DBS entails a risk of hemorrhage, transient ischemic attack (TIA), stroke, and death. Researchers also found that if the impulses were increased too quickly, patients would get oculomotor disturbances and vertigo.
“You couldn’t use DBS for acute treatment of cluster,” Dr. Tepper said. “And it also took a long time for the DBS to start to work in cluster headache prevention. The mean time to effectiveness was 42 days once it was on, and then it really seemed to work. If you turned it off, the clusters would come back.” One death, a hemorrhage, a stroke, and at least one TIA were reported.
Although 61% of the patients implanted seemed to benefit, the complications prompted researchers to examine other alternatives, including peripheral stimulation. “Small open-label case series do not justify widespread clinical use, but probably do justify a large prospective trial,” Dr. Tepper said. “Since the available evidence is from case series, the evidence is at level U—no randomized controlled data—but we think it works because if you turn it off, the clusters come back.”
| AAN CLASSES OF STUDIES AND LEVELS OF EVIDENCE |
|---|
| Class I: A randomized controlled trial in which the baseline demographics are similar between the two groups, inclusion criteria are clearly stated, there are a primary outcome and outcome measures that are similar to those previously used so that comparisons are equivalent, and more than 80% of the participants complete the study. |
| Class II: A randomized controlled clinical trial that lacks one criterion of a Class I study. |
| Class III: All other controlled trials, including well-defined natural history studies. |
| Class IV: Studies not meeting Class I, II, or III criteria, including consensus or expert opinion. |
| Level A: Established evidence from at least two Class I trials |
| Level B: Probable effectiveness based on one Class I trial or at least two Class II trials. |
| Level C: Possible effectiveness based on one Class II trial or at least two Class III studies. |
| Level U: Inadequate data to support or refute use. |
Vagal Nerve Stimulation
The evidence for implantable VNS for cluster is even more scant. Two patients were implanted for chronic cluster. “They both responded, but the outcome measure was a disability measure that is primarily used for migraine, not validated in cluster, so the evidence level is U for implantable VNS for cluster,” said Dr. Tepper.
“The noninvasive VNS is called GammaCore, and there has been one open-label study presented in abstract form,” Dr. Tepper said. “We don’t have a complete peer-reviewed paper.” There were 21 patients in this study: 12 with chronic cluster and nine with episodic cluster. “The device may have preventive as well as acute effects, so in this study both were looked at,” Dr. Tepper noted.
For acute use, two to four cycles of 90 seconds each were given at the start of an attack ipsilateral to the pain. About two-thirds of the acute attacks seemed to respond; 47% of the attacks responded with pain freedom within 15 minutes. Tachyphylaxis did not appear to occur, and the effect persisted for six to 12 months. Four patients were able to stop their acute cluster medicine, two were able to stop oxygen, and four were able to stop taking triptans. “If this were to hold up in a randomized controlled trial, it would have a major impact on cluster headache treatment,” Dr. Tepper said.
For preventive use, two 90-second cycles were given twice daily—morning and afternoon—ipsilateral to the pain, and this treatment showed a significant decrease in 24-hour frequency of cluster attacks. Before the treatment, there were as many as four attacks per 24 hours; afterward, there were 2.5 per 24 hours, and that difference was statistically significant.
“So where do we stand? All patients who participated would recommend that other cluster patients try it,” Dr. Tepper said. Adverse events were local and short-lived. The mean estimated improvement was about 50%. Four randomized controlled trials are under way right now—three for cluster and one for chronic migraine. The noninvasive VNS device has a CE mark in Europe. “Right now the evidence level is still U for both migraine and cluster—we have no randomized controlled data,” Dr. Tepper said. “But stay tuned for next year because this is an area of great interest to clinicians and patients alike.”