Sphenopalatine Ganglion Stimulation for Refractory Cluster Headache

Emerging evidence suggests that sphenopalatine ganglion stimulation may be an effective treatment for refractory cluster headache.

Cluster headache (CH) is a rare and disabling form of primary headache that affects an estimated 0.3% of the population and  is the most common type of trigeminal autonomic cephalalgia. The prevalence of CH is 3 times higher in men vs women and onset typically occurs between age 20 and 40.1

CH attacks are characterized by severe, unilateral pain in the orbital, supraorbital, or temporal region, or any combination of the three.2 CH-associated pain is so extreme that the disorder has been dubbed “suicide headache,” as it has been associated with suicidal ideation.3 

During bouts of CH, attacks may occur up to 8 times per day and generally last  from 15 to 180 minutes. More than 80% of CH are episodic, with bouts lasting between 7 days and 1 year, and periods of remission of at least 1 month between bouts. “Frequently, episodic CH has a striking circannual periodicity, with the bouts occurring in the same month of the year,” wrote the authors of a recent review on the topic.3 In chronic CH, patients do not experience remission, or periods of remission lasting less than 1 month. 

“[A CH] attack is regarded as an activation of the trigemino-autonomic reflex, and the posterior hypothalamus is supposed to play a pivotal role, probably via a trigemino-hypothalamic pathway,” according to the review authors. CH attacks are characterized by the presence of one or more ipsilateral cranial autonomic symptoms that include edema of the eyelid, rhinorrhea, miosis, ptosis, and lacrimation. Patients also frequently report feeling agitated and restless during attacks. 

There are 2 validated acute treatments in CH pain as outlined in the 2016 American Headache Society guidelines: oxygen inhalation and subcutaneous sumatriptan.4 In addition, therapies that may reduce the intensity and frequency of CH attacks include lithium, verapamil, and corticosteroids. 

In patients with refractory CH, neuromodulation may offer some relief. The sphenopalatine ganglion (SPG) has been implicated in the cranial autonomic symptoms associated with CH, and emerging evidence supports the effectiveness of treatments targeting the SPG.

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It has been proposed that CH attacks involve “activation of the parasympathetic superior salivatory nucleus and SPG parasympathetic fibers, inducing neuropeptides release … and vasodilatation of the cerebral and dural blood vessels, which activate meningeal nociceptive fibers projecting to the trigeminal ganglion and nuclei,” resulting in referred periorbital pain, as explained in the review. 

The review authors examined the limited evidence regarding the efficacy of SPG stimulation with a neuromodulaton device implanted in the pterygopalatine fossa. 

Following is a summary of the results from these studies.

  • In a multicenter pilot study, 28 patients with refractory chronic CH were randomly assigned to receive 15-minute full stimulation or 1 of 2 nonactive techniques: subperception stimulation or sham stimulation.5 Full stimulation led to the alleviation of pain in 67.1% of patients compared with 7.3% and 7.4% of subperception and sham stimulation, respectively (P <.0001). 
  • Long-term results from the 24-month open phase of the this study (n=33) indicated efficacy in 65% of patients.6 
  • A >50% reduction in the frequency of attacks was observed in 35% of patients, indicating the potential for repeated SPG stimulation as a preventive treatment. 
  • In a cohort of 99 patients, an evaluation of the device’s safety revealed facial sensory disturbances, transient allodynia, and infection in 67%, 3%, and 5% of patients, respectively.7

Although further research is needed, SPG stimulation has “showed its efficacy to abort CH attacks vs placebo stimulation, suggesting that it is particularly adapted for patients with CH] who are not sufficiently improved by currently available abortive treatments such as sumatriptan and oxygen,” the review authors concluded. 

Clinical Pain Advisor spoke with Mia T. Minen, MD, MPH, assistant professor of neurology and director of Headache Services at New York University Langone Medical Center, who offered the following thoughts on the potential for SPG stimulation as a treatment for CH.

I think that the mechanism behind SPG stimulation makes intuitive sense. For another common primary headache type — migraine — I have traditionally used intranasal lidocaine, which patients self-administer, but it is hard and cumbersome to use. I tell patients that it is not a cure and may not be very effective, but it may reduce the pain intensity and allow other medications to work. Thus, I think it is helpful to have better methods for reaching this area — which is so close to the trigeminal nerve — which we believe is implicated in pain.

It can often be hard to objectively measure response to pain. In a small open label study, the SPG stimulator appeared to reduce the requirement that pain is present in order to treat acute attacks. For example, in 79% of attacks, patients did not report needing to use acute medication.

While these results are promising, additional larger studies need to be done. As the review authors point out, I agree it is necessary to compare the SPG stimulator with standard abortive treatments — sumatriptan injection and/or inhaled oxygen — to examine whether the outcomes are the same, inferior, or superior. Cost-benefit analyses are also needed.

Disclosures: D Fontaine and M Lanteri-Minet are consultants for Autonomic Technologies and Medtronic.

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  1. American Migraine Foundation. Cluster headache. https://americanmigrainefoundation.org/understanding-migraine/cluster-headache. Accessed March 29, 2018.
  2. Gooriah R, Buture A, Ahmed F. Evidence-based treatments for cluster headache. Ther Clin Risk Manag. 2015;11: 1687-1696.
  3. Fontaine D, Santucci S, Lanteri-Minet M. Managing cluster headache with sphenopalatine ganglion stimulation: a review. J Pain Res. 2018;11:375-381.
  4. Robbins MS, Starling AF, Pringshein TM, Becker WJ, Schwedt TJ. Treatment of cluster headache: The American Headache Society Evidence-Based Guidelines. Headache. 2016;56:1093-1096.
  5. Schoenen J, Jensen R, Lantéri-Minet M, et al. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia. 2013;33(10):816-830.
  6. Jurgens T, Barloese M, May A, et al. Long-term effectiveness of sphenopalatine ganglion stimulation for cluster headache. Cephalagia. 2017;37(5):423-434. 
  7. Assaf A, Hillerup S, Rostgaard J, et al. Technical and surgical aspects of the sphenopalatine ganglion (SPG) microstimulator insertion procedure. Int J Oral Maxillofac Surg. 2016; 45(2):245-254.