Curr Pain Headache Rep (2014) 18:433 DOI 10.1007/s11916-014-0433-4

TRIGEMINAL AUTONOMIC CEPHALALGIAS (M MATHARU, SECTION EDITOR)

Role of Sphenopalatine Ganglion Stimulation in Cluster Headache Tim P. Jürgens & Arne May

# Springer Science+Business Media New York 2014

Abstract Cluster headache attacks are characterized by extreme unilateral pain mostly in the first trigeminal branch and an ipsilateral activation of the cranial parasympathetic system, pointing to a relevant role of the cranial parasympathetic system in the pathophysiology, and therapy of cluster headache. Based on animal experiments and several interventions of the sphenopalatine ganglion (such as an aesthetic or alcoholic blocks and radiofrequency ablation) in cluster headache patients, stimulation of the sphenopalatine ganglion (SPGS) as the major efferent peripheral parasympathetic structure was established with an encouraging abortive effect on acute attacks and a frequency reduction over time. In this review, the clinical data and potentially underlying pathophysiological concepts of SPGS are discussed in detail, which in brief point to a relevant role of the parasympathetic system both in the induction and termination of attacks. Keywords Cluster headache . Sphenopalatine ganglion . Stimulation . Neuromodulation . Trigemino-parasympathetic reflex

Introduction Cluster headache, along with the other trigeminal autonomic cephalgias, is characterized by a transient parasympathetic activation (besides sympathetic inhibition) and strictly halfsided ipsilateral headaches in the first trigeminal division (V1) as outlined by the current diagnostic criteria [1]. Signs of This article is part of the Topical Collection on Trigeminal Autonomic Cephalalgias T. P. Jürgens : A. May (*) Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 22529 Hamburg, Germany e-mail: [email protected]

parasympathetic innervation include lacrimation, conjunctival injection, nasal congestion, and rhinorrhea. Attacks typically last 15–180 minutes, often repeatedly up to 8 times per day. In the majority of patients (around 85 %), attacks occur in bouts of several weeks once or twice per year separated by attackfree intervals of at least 4 weeks. The chronic form is characterized by attacks occurring over at least 1 year with remission periods of less than 4 weeks. While a sufficient reduction of attack frequency can be achieved in the majority of patients with preventative drug treatment (verapamil, lithium, topiramate, and methysergide) and most patients respond well to acute treatment with triptans and/or oxygen, an estimated proportion of 10 %–15 % remain refractory to standard preventive drug treatment. This can be observed in episodic cluster headache as well; however, most of these patients rely on acute treatment because of the episodic nature of their attacks. Interventional neuromodulatory approaches have been used in refractory primary headaches in the last decade following deep brain stimulation of the posterior hypothalamus in chronic cluster headache [2] and occipital nerve stimulation in what was initially thought to be occipital neuralgia (but later considered to be chronic migraine) [3–5]. Subsequently, various interventional and, more recently, noninterventional neuromodulatory treatments have been propagated for several primary headache types (for further review see [6, 7]). Response rates of ≥50 % with sustained long-term efficacy have been reported in patients with chronic cluster headache for posterior hypothalamic deep brain stimulation (phDBS) and occipital nerve stimulation (ONS). Acute stimulation using these approaches has rarely been examined or was not effective in cluster headache [8]. The cluster headache armamentarium has recently been augmented by stimulation of the sphenopalatine ganglion (SPG). The scientific rationale for targeting the SPG is based on the close relation between headache and autonomic activation in this headache type.

433, Page 2 of 6

Pathophysiology of Cluster Headache The activation of the cranial parasympathetic system is mirrored by a release of vasointestinal peptide (VIP) and acetylcholine during cluster headache attacks [9]. As it is thought to subsequently activate nociceptive trigeminal afferents in the meningeal vessels (Fig. 1), the functional anatomy and the interplay of the parasympathetic and the trigeminal system are explained below. Activation of the cranial parasympathetic system occurs by activation of the superior salivatory nucleus (SSN) in the brain stem in vicinity of the trigeminocervical complex (TCC). Pregang l i o n i c e ff e r e n t s f r o m t h e S S N p r o j e c t t o t h e sphenopalatine ganglion (SPG) located in the pterygopalatine fossa (PPF) via the greater petrosal nerve. Together with sympathetic fibers from the carotid plexus they form the Vidian nerve, which exits from the Vidian canal close to the SPG. The majority of parasympathetic preganglionic fibers synapse to postganglionic fibers within the SPG, while sympathetic fibers cross the SPG without synapsing. A bundle of maxillary nerve fibers projecting from the foramen rotundum to the SPG form the sensory root [10] and subsequently innervate the posterior nasopharynx via the lesser palatine nerves. The postganglionic efferent parasympathetic fibers then innervate both facial glands and mucosa (such as the lacrimal gland and the nasopharyngeal mucous membranes) and the meningeal vessels [11]. Experimental parasympathetic stimulation with low frequencies around 10 Hz causes dilation of meningeal vessels [12], alters the blood brain barrier [13], and induces plasma protein extravasation, which serves as a model for neurogenic inflammation [14] (for a recent comprehensive review on the intracranial effects of low-frequency experimental SPG stimulation see [15]) The resulting activation of trigeminal nociceptors of the first division (V1) causes activation in the TCC and interneurons projecting to higher centers and further activates the SSN via the trigeminoparasympathetic reflex (TPR) arc, which is limited to V1 afferents, but not V2 or V3 [16, 17]. Thus, a “vicious circle” could be formed raising the question if the activation arises primarily in the SSN or rather in higher brain centers associated with cluster headache, such as the posterior hypothalamus (PH). Neuro-endocrine findings have long suggested a relevant role of the hypothalamus based on the clinical picture of trigemino-autonomic cephalgias (TAC) and their abnormal profile of cortisone, melatonin and other hypothalamically-entrained hormones [18, 19], This was later confirmed by neuroimaging studies showing structural and functional abnormalities in this region [20, 21]. Therefore, it is conceivable that the PH activates the SSN (and possibly the trigemino-cervical complex), which induces a cluster headache attack

Curr Pain Headache Rep (2014) 18:433

resulting in the above described vicious circle, which is maintained as long as the centrally (ie, hypothalamic) driven activation is maintained.

Clinical Data The common concept of interventions targeting the SPG is a disruption of the interplay of the parasympathetic with the trigeminal system. Modulation of trigeminal afferents such as supra- or infra-orbital nerve stimulation has been suggested as a preventive treatment in chronic cluster headache [22], but acute efficacy has not been examined using a valid prospective, randomized design. However, at least acute transcutaneous supraorbital nerve stimulation does not abort acute migraine attacks [23]. Furthermore, Matharu and colleagues reported a patient with persistent cluster headache attacks even after complete transection of the ipsilateral trigeminal sensory root [24], suggesting that parasympathetic approaches may be more effective in the acute treatment of cluster headache. Based on the prominent parasympathetic signs during acute cluster headache attacks, first approaches to block parasympathetic transmission on the level of the SPG date back to the early 20th century to patients with “Sluder’s neuralgia”, a headache syndrome with trigeminal-autonomic activation closely resembling (if not identical with) cluster headache. In the following years various ablative and nonablative approaches have been suggested including alcohol blocks with a relevant pain relief in 85 % of the 120 patients [25], blocks with local anesthetics [26] and steroids [27], intranasal lidocaine [28], radiofrequency ablation [29], ganglionectomy [30], and gamma knife surgery [31]. However, the majority of these procedures are invasive, ablative, nonadjustable, and achieve only temporary relief. Intrigued by the therapeutic efficacy of SPG interventions and a promising case report [32], 2 small pilot trials examined the effects of acute percutaneous stimulation of the SPG (SPGS) with a removable electrode in 5 patients with cluster headache and 10 patients with migraine. In patients with cluster headache, SPGS effectively aborted >60 % of attacks within a few minutes after onset of stimulation [33], likewise in 50 % of attacks in migraine patients [34]. These findings led to the development of a miniaturized neurostimulator (Fig. 2), which is implanted via a transoral approach with an incision of the buccal gingiva to the midface and anchored at the zygomatic process of the maxilla [35]. This allows positioning of the electrode lead in the PPF with the tip in close vicinity of the SPG. The stimulator is controlled and powered transcutaneously by radio frequency (RF) waves and, thus, requires no extended leads or battery-driven impulse generators. Programming is based on the recommendations by Narouze [36] with the aim to evoke paresthesias deep behind the root of the nose and in the soft palate with

Curr Pain Headache Rep (2014) 18:433

Page 3 of 6, 433

Cerebrum SN

HT

phDBS

Meningeal vessels TPR SSN

TG TCC

Brainstem SPG

ONS

Lacrimal gland, Nasopharyngeal mucosa SPGS Fig. 1 Sphenopalatine ganglion stimulation and its putative mechanism of action. A centrally driven parasympathetic activation putatively originated by the posterior hypothalamus initiates a “vicious circle” consisting of parasympathetic efferents projecting from the SSN via the SPG to meningeal vessels in the dura mater, where a neurogenic inflammation activates trigeminal nociceptive afferents. Subsequently, the trigeminocervical complex is activated and, in turn, the SSN via the trigeminoparasympathetic

reflex (red arrows). This process is maintained as long as the central activation of the SSN persists or an intervention blocks nociceptive transmission. HT hypothalamus, ONS occipital nerve stimulation, phDBS posterior hypothalamic deep brain stimulation, SN suprachiasmatic nucleus, SPG sphenopalatine ganglion, SPGS sphenopalatine ganglion stimulation, SSN superior salivatory nucleus, TCC trigeminocervical complex, TG trigeminal ganglion, TPR trigeminal-parasympathetic reflex

frequencies around 80–120 Hz and patient controlled intensity. In a randomized double-blind multicenter study on 32 patients with refractory chronic cluster headache active stimulation during cluster headache attacks evoking paresthesias in the above target areas was compared with subthreshold and sham (ie, no) stimulation [35]. Active stimulation fully aborted or substantially attenuated 67 % of all analyzed attacks of the 28 patients who entered the final analysis compared with subthreshold (7 %) and sham (7 %) stimulation (P

Role of sphenopalatine ganglion stimulation in cluster headache.

Cluster headache attacks are characterized by extreme unilateral pain mostly in the first trigeminal branch and an ipsilateral activation of the crani...
329KB Sizes 4 Downloads 3 Views