Neurostimulation for the Treatment of Cluster Headache

Special Article - Pain Management

Austin J Anesthesia and Analgesia. 2015; 3(1): 1041.

Neurostimulation for the Treatment of Cluster Headache

Lavano A*, De Rose M, Guzzi G, Romano M, Della Torre A, Vescio G, Deodato F and Volpentesta G

Department of Neurosurgery, University of Magna Graecia, Italy

*Corresponding author: Lavano A, Department of Neurosurgery, University “Magna Graecia”, Campus “S. Venuta” of Germaneto, Viale Europa, 88100 Catanzaro, Italy

Received: May 28, 2015; Accepted: September 14, 2015; Published: September 22, 2015


Neurostimulation procedures have been introduced quite recently as an alternative treatment of intractable chronic headaches mainly because they are less invasive than the surgical ablative techniques used in the past years. We review the current neurostimulation approaches to the management of chronic cluster headache which is an extremely severe and debilitating trigeminoautonomic pain syndrome. The results of hypothalamic deep brain stimulation, occipital nerve stimulation and sphenopalatine ganglion stimulation are promising, but we do not know which is more effective, because these procedures are still investigational. Many other target are being were used and new devices are being developed.

Keywords: Cluster headache; Neurostimulation; Deep brain stimulation; Occipital nerve stimulation; Sphenopalatine ganglion stimulation; Hypothalamus


CH: Cluster Headache; hDBS: hypothalamic Deep Brain Stimulation; ONS: Occipital Nerve Stimulation; SPGS: Sphenopalatine Ganglion Stimulation; drCCH: drug-resistant Chronic Cluster Headache; SCN: Suprachiasmatic Nucleus; CCH: Chronic Cluster Headache; SONS: Supraorbital Nerve Stimulation; VNS: Vagal Nerve Stimulation; tVNS: transcutaneous Vagal Nerve Stimulation; SCS: Spinal Cord Stimulation


Cluster Headache (CH) is a severe and painful condition that is characterized by short-lasting, severe, strictly unilateral pain along the distribution of the first branch of the trigeminal nerve, accompanied by prominent cranial, parasympathetic, autonomic features with circadian and circannual regularity [1]. The diagnosis is still clinical and a recent study highlighted a male prevalence [2]. 10- 20% of patients seem to be resistant to all pharmacological treatments [3]. Many ablative techniques, such as radiofrequency lesioning or gamma-knife lesioning of the trigeminal nerve or of sphenopalatine ganglion, trigeminal tractotomy, have been used to treat these patients with varying results and with permanent and severe complications. Neurostimulation techniques have been introduced fairly recently to treat completely drug-resistant Chronic Cluster Headache (drCCH). Treatment with these techniques remains investigational, but it represents a valid alternative to destructive surgical procedures. Hypothalamic Deep Brain Stimulation (HDBS), Occipital Nerve Stimulation (ONS), Sphenopalatine Ganglion Stimulation (SPGS) and some others seem to be a nondestructive, reversible and adaptive way of helping drCCH patients.

Anatomy of trigeminal system and pathophysiology of cluster headache

The trigeminal system provides the primary sensory innervation of the face, innervates the dura mater and cranial blood vessels, where its fibers endings can promote an inflammatory response by releasing vasoactive peptides that are involved probably in the generation of headache [4]. The trigeminal nerve originates from the lateral Pons and it divides into three branches: the ophtalmic, the maxillary and the mandibulary one. The posterior region of the head is innervated by the greater, lesser and third occipital nerves, that arise from the spinal nerve of the occipital plexus [5]. Goadsby and Hoskin demonstrated that there is a connection between the cervical and trigeminal system [6]. This anatomical and functional relation might explain the nociceptive frontal activation from the cervical region. From this theory, the neuromodulation of occipital nerves and nerves that supply the face might provide improved relief from headache pain not only in the territories that it innervates itself, but also in those innervated by the trigeminal nerve [7]. The hypothalamus plays an important role in the pathophysiological mechanisms behind CH [8,9]. Neuroimaging has suggested an abnormality or dysfunction of the posterior hypothalamus, especially of the Supra Chiasmatic Nucleus (SCN) [10,11]. The SCN is responsible for controlling the circadian rhythmicity of hormone release and sleep-wakefulness cycles. It has also projections to the pineal gland, responsible for melatonin production [12,13]. It has been demonstrated that the circadian pattern of melatonin and cortisol are altered in CH patients [14]. PET studies showed significant activation of the ipsilateral, posterior, hypothalamic gray matter only in CH patients inside a cluster period, suggesting a specific role for the hypothalamus in CH. Moreover a voxel-based, morphometric, magnetic resonance study found a significantly increased density and volume of the gray matter region corresponding to the inferior posterior hypothalamus [15,16].

Review of the literature

Neuromodulation involves the exogenous application of electrical current as a method of influencing pain signals for the purpose of reversible modification of the nociceptive system function, using implantable electrodes and generator devices [17]. The publication of the “Gate Control Theory” by Melzack and Wall in 1965 offered a theoretical foundation for considering direct electrical stimulation of the spinal cord and peripheral nerves as a potential treatment for chronic pain [18]. Its use in headache disorders increased in the 1990s with Weiner and Reed, who first described a percutaneous approach for Occipital Nerve Stimulation (ONS) in presumed occipital neuralgia [19].

Many neuromodulation targets for treating Chronic Cluster Headache (CCH) are described in literature. The following discussion will outline some of these targets.

Hypothalamic Deep Brain Stimulation (hDBS) in CCH (Table 1): The above mentioned evidence of hypothalamic involvement in CH pathophysiology led to the use of hypothalamic DBS in drCCH patients. A lead is positioned in the posterior, inferior hypothalamus, ipsilaterally to the side of the facial pain. Leone and Broggi treated 16 drCCH patients, 14 with an unilateral DBS, 2 with a bilateral implant. The mean duration of chronic CH phase was of three years. The response rate (defined by improvement of > 50%) was 81% - the best available result - with ten patient’s pain free and three patients with sporadic attacks [20,21]. Schoenen performed unilateral hDBS in six patients with a response rate of 50%. This was a pilot study [22]. The result was equaled by Bartsch with six patients treated unilaterally [23]. Sillay treated eight patients, but the data available were only for five patients. He performed an unilateral hDBS with a response rate of 63% [24]. Fontaine performed the first sham-trial involving unilateral hDBS in drCCH patients. This was a randomized, prospective, crossover study involving eleven patients, although the crossover period was too short (only one month) to appreciate significant changes in headache attacks. The response rate was of 55% [25]. Brittain and Owen treated 3 patients with an unilateral HDBs with a 100% response rate [26,27]. Hidding and May reported a single unilateral hDBS case, after which a frontal bilateral headache arose and disappeared when stimulator was turned off [28]. Seijo performed five unilateral hDBS on a modified target to avoid hemorrhagic complications due to the proximity to the third ventricle. The response rate was 100%, but three patients had permanent euphoria and myosis [29].