Neurostimulators for the Treatment of Primary Headaches

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

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

Sphenopalatine Ganglion Stimulation

The sphenopalatine ganglion (Meckel's ganglion) is an extracranial autonomic ganglion present in the pterygopalatine fossa close to the sphenopalatine foramen. It has connections with the trigeminovascular system, superior salivary nucleus and hypothalamus, and has been targeted by techniques such as anesthetic block, radiosurgery and γ-knife, mainly to treat cluster headache.

An open study on 120 cluster headache cases reported that alcohol injection was effective in 85% with follow-up from 6 months to 4 years.^[78] Two more recent studies on patients with chronic cluster headache and intractable migraine used a percutaneous infrazygomatic approach to place a needle at the sphenopalatine ganglion under fluoroscopic guidance during ongoing headache.^[79,80] Electrical stimulation at various settings was performed at maximum headache intensity with a temporary stimulating electrode. Complete pain resolution was obtained in 11 of 18 cluster headache patients almost immediately, and 50% relief was obtained in four other patients.^[79] Stimulation suppressed or relieved migraine headache in five of ten patients.^[80]

In a multicenter study on patients with refractory chronic cluster headache, the efficacy of an implantable on-demand sphenopalatine ganglion neurostimulator was tested as a treatment for acute cluster headache attacks.^[81] The experimental period was 30 attacks or a maximum of 8 weeks. Each cluster headache attack was randomly treated with either full, subperception or sham-stimulation. Pain relief at 15 min following stimulation and device- or procedure-related serious adverse events were evaluated. A total of 28 of 32 enrolled patients completed the experimental period. Pain relief was achieved in 67.1% of full stimulation-treated attacks compared with 7.4% of sham-treated and 7.3% of subperception-treated attacks. A pain-free condition was achieved in 34.1% of attacks with full stimulation compared with 1.5% with sham stimulation. At baseline, mean cluster headache attack frequency was 17.4 per week (range: 4–70) which reduced to 12.5 (range: 0–96) over the experimental period. A total of 12 of 28 patients (43%) had a greater than 50% frequency reduction during the experimental period. Altogether, 81% experienced transient, mild/moderate loss of sensation within distinct maxillary nerve regions; 65% of events resolved within 3 months.

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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.