Neurostimulators for the Treatment of Primary Headaches

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

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

Abstract and Introduction

Abstract

Neurostimulation techniques have increased our therapeutic armamentarium, providing additional options for the treatment of patients with drug-resistant headache. Occipital nerve stimulation can be considered in drug-resistant chronic cluster headache and, with more caution, in drug-resistant chronic migraine. Approximately 12 years after its introduction, hypothalamic stimulation is a valid option for drug-resistant chronic cluster headache to be considered when occipital nerve stimulation fails. Several other peripheral stimulation approaches (in addition to occipital nerve stimulation) have been introduced in recent years; however, for the most part, appropriate studies supporting their efficacy are lacking. Transcranial magnetic stimulation, transcutaneous supraorbital nerve stimulation, sphenopalatine ganglion stimulation and vagal nerve stimulation have all been tried, but results are not wholly convincing, and more extensive evaluations are required.

Introduction

Headaches without an identifiable underlying cause (primary headaches) affect approximately 45% of the general population^[1] and have a considerable socioeconomic impact.^[2,3] Severe chronic headaches, where patients experience daily or almost-daily headache attacks, are highly disabling and have been estimated to affect approximately 1.4–2.2% of the population.^[4] Although effective treatments are available for most primary headaches, a proportion of chronic headache sufferers are poor responders or intolerant to pharmacological treatments.

Neurostimulation techniques for treating primary headaches range from invasive deep brain stimulation to less invasive peripheral implantation and stimulation, and even less invasive transcranial stimulation. Central and peripheral neurostimulation techniques that have been applied to headache are extensively reviewed here; transcranial techniques are also considered. Their mechanisms of action and rationale for use are discussed, and the evidence for their effectiveness and safety is evaluated.

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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.