Neurostimulators for the Treatment of Primary Headaches

Massimo Leone; Alberto Proietti Cecchini; Angelo Franzini; Gennaro Bussone

Future Neurology. 2013;8(4):457-467.

Transcranial Magnetic Stimulation

In transcranial magnetic stimulation (TMS) a rapidly changing magnetic field is applied to the surface of the scalp either as a single pulse or as trains of repeated pulses. Since single-pulse TMS can disrupt cortical spreading depression in animals it was reasoned that it might be therapeutic in migraine, and several studies have been conducted.^[66–71] Clarke et al. compared the effect of two single pulses of high- and low-intensity TMS in migraine patients both with and without aura.^[67] All the migraine with aura patients reported that TMS had an immediate effect on their headache, and 32% of all patients had no headache recurrence 24 h after stimulation.

In 2010, Lipton et al. published results of a randomized sham-controlled study on 164 migraine with aura patients.^[68] They used a portable TMS device, delivering two single pulses at 30-s intervals, to stimulate the occiput within an hour of aura onset. A total of 39% of TMS and 22% of sham-stimulated patients were pain free at 2 hours. The difference was significant, and sustained pain-free rates at 24 h and 48 h were also significantly better in the TMS group. However the global assessment of relief was better in the sham arm than the TMS arm; and nausea, photophobia, phonophobia and use of acute medication did not differ between groups. In view of the small difference in efficacy between real and sham stimulation, the utility of TMS in acute migraine with aura cannot be considered established.

Since a functional magnetic imaging study had shown that the left dorsolateral prefrontal cortex exerts an inhibitory control on pain pathways in humans, Brighina et al. investigated high-frequency (20 Hz) repetitive TMS to this area in a randomized study on 11 chronic migraine sufferers, with six receiving TMS and five receiving sham stimulation.^[69] While control patients experienced no changes in outcome measures, those who received TMS had significant reductions in attack frequency, headache index and number of abortive pills used in the month after treatment compared with the month before treatment; the effects lasted for up to 2 months. However, in another study on 13 patients with chronic migraine, repetitive TMS (10 Hz), also applied to the dorsolateral prefrontal cortex, proved less effective than sham stimulation after 2 months.^[70]

Teepker et al. applied 1 Hz repetitive TMS (two trains of 500 pulses at the motor threshold on 5 consecutive days) over the vertex in 27 patients with episodic migraine with or without aura, based on the rationale that low-frequency repetitive TMS may return a hypothesized hyperexcitable migrainous brain to normal.^[71] The number of attacks and days with attacks did not differ significantly between the TMS group and sham stimulation group. Further studies are required to determine whether or not TMS is effective in migraine.

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Table 1. Summary of results of hypothalamic stimulation studies in drug-resistant chronic cluster headache.
Study (year)	Implanted patients (n)	Mean follow-up (years)	Improved patients (n)^†	Improved (%)	Ref.
Leone et al. (2001, 2006 and 2013)	19	8.7	12	71^‡	[7,9,20]
Schoenen et al. (2005)	4	4	2	50	[8]
Starr et al. (2007)	4	1	2	50	[12]
Owen et al. (2007)	1	0.7	1	100	[13]
Bartsch et al. (2008)	6	1.4	3	50	[16]
Fontaine et al. (2010)	11	1	6	55	[17]
Seijo et al. (2011)	5	2.8	3	60	[19]
Hidding and May (2011)	1	NR	0	0	[18]
D'Andrea et al. (2006)	3	2.5	2	67	[10]
Benabid et al. (2006)	1	1	1	100	[11]
Mateos et al. (2007)	2	1	2	100	[15]
Black et al. (2007)	2	2.6	2	100	[14]
Nikka et al. (2005)^§	2	2	0	0
Total	61	2.4	36	61

^†At least 50% improvement in headache frequency and/or intensity.
^‡Percentage calculated from 17 of out 19 patients: one patient died for reasons other than the neurostimulator and in another patient the electrode was removed owing to infection.
^§[Nikka et al., Pers. Comm.].
NR: Not reported

Table 2. Summary of results of occipital nerve stimulation studies in drug-resistant chronic cluster headache.
Study (year)	Implanted patients (n)	Follow-up (months)	Improved patients (n)^†	Improved (%)	Ref.
Magis et al. (2007 and 2011)	15	36.8	12	80	[43,52]
Burns et al. (2009)	14	17.5	5	36	[44]
Proietti Cecchini et al. (2009)	13	21	8	62	[45]
Lara Lara et al. (2009)	6	6–15	4	67	[46]
de Quintana-Schmidt et al. (2010)	4	6	4	100	[47]
Salom and Lainez (2010)	14	NR	7	50	[48]
Müller et al. (2011)	10	12	9	90	[49]
Fontaine et al. (2011)	13	14.6	10	77	[50]
Strand et al. (2011)	3	12	2	67	[51]
Total	92	17.1	61	66

^†At least 50% improvement in headache frequency or intensity.
NR: Not reported.

Sidebar

Executive Summary

Occipital Nerve Stimulation

Occipital nerve stimulation has achieved good results in drug-resistant chronic cluster headache, but less favorable results are achieved in chronic migraine. Occipital nerve stimulation is widely considered to be the first choice neurostimulation procedure for chronic cluster headache.

Hypothalamic Stimulation

Hypothalamic stimulation is an invasive procedure for drug-resistant chronic cluster headache and other trigeminal autonomic cephalalgias (short-lasting neuralgiform headache attacks with conjunctival injection and tearing, and paroxysmal hemicrania). This technique is tolerable and effective in approximately 60% of treated patients many years after implantation.

Transcranial Magnetic Stimulation

Transcranial magnetic stimulation efficacy has been investigated in migraine, both chronic and episodic, and with and without aura. Results are less favorable than with other neurostimulation procedures.

Transcranial Direct Current Stimulation

Transcranial direct current stimulation seems to have a certain efficacy in reducing migraine intensity rather than frequency.

Cervical Spinal Cord Stimulation

Cervical spinal cord stimulation is a rather invasive procedure that in one study reduced both frequency and intensity of chronic cluster headache.

Sphenopalatine Ganglion Stimulation

Preliminary findings suggest that stimulation can rapidly control ongoing cluster headaches. Surgery-related local adverse events are claimed to be as frequent as with other maxillofacial surgical procedures.

Other Types of Nerve Stimulation

Vagal nerve stimulation to treat drug-resistant chronic migraine and cluster headache may be justifiable when other conditions, such as epilepsy or depression, are also present.

Conclusion

Interest in neurostimulation techniques to treat intractable headache conditions has burgeoned in recent years, but enthusiasm should be tempered as most studies have been open. Although many of these techniques show effectiveness, they should be used with caution: rigorous selection criteria are necessary, and the advantages and disadvantages, including costs, should be extensively evaluated on an individual basis, implying more than usual attention to the patient by the physician.