Neurostimulation devices in headache treatment - 2013
Dr Jan Hoffmann and Dr Weera Supronsinchai
Neurostimulation devices have been of increasing interest for the treatment of primary headaches in recent years. After initial experiences with deep brain stimulation for the treatment of refractory cluster headache, which has been hampered by severe side effects, several new minimally invasive and non-invasive devices are being tested for migraine and other primary headaches. Results from initial experiences and recent clinical trials have been presented at the 2012 EHMTIC.
Regarding the minimally invasive neurostimulation devices, Prof Schoenen from the Headache Center in Liège, Belgium, presented results from a clinical trial testing the efficacy of sphenopalatine ganglion (part of the parasympathetic nervous system responsible for activities that occur when the body is at rest) stimulation using the ATI® implantable microstimulator which is implanted into the pterygopalatine fossa (a small bony cavity shaped roughly like a funnel near the base of the skull) to disrupt the parasympathetic reflex. In this system stimulation is initiated using a portable remote control unit. The results show that the 27 patients who took part reported that pain relief could be achieved in 67% of treated headache attacks. However, the study has a small sample and patients experienced a transient numbness at the stimulation site, affecting the blinded design of the study, so study participants knew whether they had the real or the ‘dummy’ stimulator.
Non-invasive devices presented at EHMTIC followed different stimulation methods. Single pulse transcranial magnetic stimulation (sTMS) has recently been tested in a clinical trial and the results suggested a weak but significant effect for the acute treatment of migraine with aura. Results from a post market study with the portable SpringTMS™ device have been presented at this year’s conference. The study involved 37 patients who recorded a total of 777 migraine attacks. A reduction of migraine pain was reported by 73% of patients and a reduction of migraine associated symptoms by 63% with no adverse events reported. The results suggest a possible efficacy of the device for the acute treatment of migraine. However, sample sizes were small and headache reporting was controversial since no objective reporting in headache diaries, as is standard for clinical trials, was available. Therefore further placebo controlled studies with larger sample
sizes and objective symptom recording have to be conducted to clarify whether TMS is effective in the treatment of acute migraine attacks.
Furthermore, initial data with the Gammacore® device for transcutaneous vagus nerve stimulation (tVNS) for the treatment for several types of primary headache was presented. While the initial data on migraine without aura (including patients with medication overuse headache) have been rather disappointing, Nesbitt et al showed results on 14 cluster headache patients (seven with episodic cluster headache, seven with chronic cluster headache) treated over 14 weeks which showed a subjective improvement of 60% in 13 patients.
However, as in the trials with the previously mentioned devices, sample sizes were very small and stimulation was not blinded as patients felt the stimulation. In addition, the Gammacore® device produced significant side effects ranging from paresthesias (pins and needles) to pain during stimulation leading to high dropout rates. Despite the fact that it is marketed as a vagus nerve stimulation device, stimulation is unspecific affecting sympathetic and parasympathetic nerves. Taken together the results show that larger trials are needed to clarify if the Gammacore® device may prove useful for the treatment of primary headaches, especially cluster headache and other trigeminal autonomic cephalalgias.
Finally, data from a multi-center, double-blind, randomised, shamcontrolled trial including 67 patients analysing the efficacy of a transcutaneous supraorbital nerve stimulator (tSNS), the Cefaly® device, for the prophylactic treatment of migraine were presented. Stimulation was perfomed for 20 minutes on a daily basis for three months. The results show a reduction of monthly migraine days and drug intake while no adverse events were observed. Therefore the results indicate that tSNS may offer an effective prophylactic migraine treatment. However, larger trials are needed to clarify its potential efficacy.
Many different types of neurostimulation are currently being tested for the acute and prophylactic treatment of primary headaches. However, existing trials are small and frequently hampered by severe methodological shortcomings. A challenge for future trials will be the achievement of true sham-controlled trials since almost all devices currently
available and the stimulation protocols used induce paresthesias or even pain during stimulation thereby leading to a certain extent of unblinding of the treated individual. With these problems solved, neurostimulation devices might finally offer a migraine-specific preventive therapy.