Sphenopalatine Ganglion Stimulation
A randomized controlled trial of the Autonomic Technologies implanted SPG stimulator device was published in Cephalalgia in 2013. A preimplant baseline measurement was followed by the implant and stabilization. Next came the experimental period with a sham and subthreshold stimulation, followed by real stimulation that lasted from three to eight weeks. The primary end point was 15-minute relief. “Here are the most up-to-date numbers,” Dr. Tepper said. Data from 32 patients with experimental stimulation were published, an additional 11 subjects were subsequently recruited, and 24 completed 18 months of follow-up. At the end of the experimental period, 769 attacks were analyzed; 55% of the attacks achieved pain relief at 15 minutes versus 6% with sham.
As with the noninvasive VNS device, the SPG stimulator showed effects on cluster prevention. With as-needed stimulation, the average number of cluster attacks per week decreased by 31%. Forty-two percent of the patients had close to a 90% reduction in attack frequency versus baseline. “It was a nice problem to have—both an acute and a preventive outcome,” Dr. Tepper commented. Nearly 45% of the patients had a reduction in their acute medication use; 39% had stopped preventive medications or reduced the dose versus baseline. “The response was maintained, so two-thirds of patients kept their responder rate, and remember the responder rate now involves acute or preventive, during the long-term follow-up,” Dr. Tepper reported. Surgery effects were considered tolerable by 83% of participants, and more than 90% of study participants said they would recommend the surgery to other patients with cluster headache.
In another study published last summer in Cephalalgia, Danish researchers found that at low frequency, SPG stimulation triggered cluster attacks. At high frequency, it either terminated or prevented cluster attacks. “It seemed the low frequency stimulation was activating the outflow from the SPG, while the high frequency was either depleting the activation, causing an information block, or somehow inhibiting outflow,” Dr. Tepper said. “This [result] is a dramatic confirmation of the pathophysiology of the device and how the SPG neuromodulation affects the cluster.”
According to Dr. Tepper, the evidence for SPG stimulation for cluster is level C—possibly effective due to one Class II trial in which 63% of patients responded with acute relief, decreased attack frequency, or both. In addition, 42% of patients had close to a 90% reduction in attack frequency; 55% achieved pain relief in 15 minutes and maintained it through 90 minutes; 46% reduced acute treatments; and there was a decrease in preventive medications as well. Headache impact decreased, quality of life increased, and these changes were sustained through 18 months.
“Right now in Europe, not only does the device have a CE mark, it is also approved as a first-line therapy, and it is reimbursed in Denmark and in Germany,” Dr. Tepper said.
Occipital Nerve Stimulation
To date, 23 patients have been treated with ONS for chronic cluster, and 12 have responded, yielding a 52% response rate. But, as Dr. Tepper pointed out, these investigations were case studies. Because no randomized controlled trial data are available, the level of evidence is U.
The Current State of Evidence
“On cluster, we have level U for DBS, but we really think it works because you can turn it on and turn it off. For noninvasive VNS, we have four randomized controlled trials under way and open-label data that are encouraging. The noninvasive VNS would be a fantastic opportunity for patients, as would the implanted SPG stimulator, which would be level C based on one Class II study. And ONS is still at level U—no randomized controlled trials,” Dr. Tepper said.
—Glenn S. Williams