Neuromodulation for Migraine—Promising, But Still Unproven
Sphenopalatine Ganglion Stimulation
The SPG has been a clinical target for headache disorders for more than 100 years, with various destructive and block techniques used, “but the benefits of what we do with the SPG from a surgical or anesthesia standpoint are often transient,” Dr. Tepper said. “Some of them are destructive, and the long-term relief often requires repeat procedures.”
For the treatment of migraine, a miniaturized implant for the SPG has been developed. It has no external batteries or wires. “Because there are no external wires, the patient stimulates by use of an external device,” said Dr. Tepper. “The device is implanted through the mouth by a good maxillofacial or plastic surgeon. The device is screwed into the skull, and the stimulator sits in the sphenopalatine fossa over the SPG, and then the patient simply stimulates.” The adverse events with the implantation of this device are similar to those of other oral procedures—maxillary nerve and sensory changes, two-thirds of which resolve in about three months. “There is a randomized controlled trial on the SPG implant and SPG stimulator for migraine going on in Europe, but there are no data on this stimulator for migraine at all—neither open-label, nor data from Europe—so we have Level U evidence,” Dr. Tepper said. “The interesting aspect of both the noninvasive VNS and implanted SPG stimulation is that by 2014 we should have data from randomized controlled trials for both these devices, and both have a tremendous upside in terms of changing our paradigm for treating migraine.”
Occipital Nerve Stimulation
Although others at the meeting spoke in more depth about ONS, Dr. Tepper provided a quick summary of the three available studies. “The first and the third did not meet their primary end points. The second study—the ONSTIM study—didn’t have a primary end point.” In the ONSTIM study, 39% of patients had at least a 50% decrease in headache frequency or severity. Looking at the results of that study, commentators have suggested that the bar may have been set too high. “Maybe we need to be looking at a little bit lower bar for efficacy because patients do respond,” Dr. Tepper said. For ONS, the level of evidence is U.
The Current State of Evidence
“Where we stand right now is with VNS, both implanted and noninvasive, Level U—we don’t have any randomized controlled data. For TMS the evidence level is B for acute treatment of migraine with aura and Level B for prevention of migraine, all comers. This device is now FDA approved for acute treatment of migraine with aura. The evidence is based on one Class 1 study each for acute and preventive treatment. For SPG stimulation, Level U—we don’t have any data at all. And for ONS, definitely Level U—failure of two studies with regard to the primary end point, and no primary end point in the other study. It is very important to keep a steely gaze on what we actually know, in terms of level of evidence at this point in migraine,” Dr. Tepper concluded.
—Glenn S. Williams
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 two Class II trials.
Level C. Possible effectiveness based on one Class II trial or two Class III studies.
Level U. Inadequate data to support or refute use.
