Neurostimulation therapy in intractable headaches

Abstract

A proportion of chronic headache patients become refractory to medical treatment and severely disabled. In such patients various neurostimulation methods have been proposed, ranging from invasive procedures such as deep-brain stimulation to minimally invasive ones like occipital nerve stimulation. They have been applied in single cases or small series of patients affected with varying headache disorders: cervicogenic headache, hemicrania continua, posttraumatic headache, chronic migraine, and cluster headache. Although favorable results were reported overall, it is premature to consider neurostimulation as a treatment with established utility in refractory headaches. At present, the most detailed clinical studies have been performed in intractable chronic cluster headache (iCCH) patients, who represent about 1% of all chronic cluster headache (CCH) patients. Various lesional interventions have been attempted in these patients, none with lasting benefits. In recent years, non-destructive neurostimulation methods have raised new hope. Hypothalamic deep-brain stimulation (hDBS) acts rapidly and has lasting efficacy, but is not without risk. Occipital nerve stimulation (ONS) was studied in two trials on a total of 17 iCCH patients. Clinical efficacy was found to be very satisfactory by most patients and by the investigators. Although slightly less efficacious than hDBS, ONS has the advantage of being rather harmless and reversible. At this stage, it should be preferred as first-line invasive therapy for iCCH. Recent case reports mention the efficacy of supraorbital (SNS) and vagal (VNS) nerve stimulation. Whether these neurostimulation methods have a place in the management of iCCH patients remains to be determined.

Introduction

In chronic neuropathic pain, neurostimulation therapy is increasingly used either as a substitute for surgical lesions or in addition to medical treatment (Cruccu et al., 2007). Although patients with chronic primary or secondary headache disorders may become resistant to medical treatment and thus severely disabled, there are very few studies of neurostimulation therapy in headache.

Only recently has occipital nerve stimulation (ONS) been studied in various headache disorders. Oh et al. (2004) were among the first to report promising results in neuropathic cervical pain (5 patients with complete, 5 with partial relief) and “transformed” migraine (9 patients with complete, 1 with partial relief). In a study comprising 8 chronic migraine, 3 chronic cluster headache (CCH), 2 posttraumatic headache, and 2 hemicrania continua patients, ONS after a mean follow-up of 19 months had on average reduced headache frequency by 38%, severity by 34%, the Migraine Disability Assessment Scale (MIDAS) by 39%, and Beck's depression inventory score by 40% (Schwedt et al., 2007). It is difficult from these contrasting results and heterogeneous patient groups to have a clear picture of the utility of neurostimulation methods in chronic headaches.

In CCH, however, prospective and more detailed clinical studies of neurostimulation therapies have been performed and, at least provisionally, give some insight into their interest and limitations. We will therefore focus on cluster headache. Cluster headache is known as the most painful primary neurovascular headache. Episodic cluster headache, as defined by the second edition of the International Classification of Headache Disorders (ICHD-II 3.1.1) (Headache Classification Subcommittee of the International Headache Society, 2004), is characterized by attacks of unilateral periorbital pain associated with ipsilateral autonomic signs occurring in bouts (clusters) of weeks or months, separated by headache-free intervals of variable length (months or years). In CCH (ICHD-II 3.1.2), which affects 10% of patients de novo or after an episodic phase (Sjaastad and Bakketeig, 2003), attacks occur over at least 1 year without remissions or with remissions lasting less than 1 month (Headache Classification Subcommittee of the International Headache Society, 2004). Besides acute therapies – sumatriptan injection, oxygen inhalation, or zolmitriptan nasal spray, in decreasing order of efficacy – CCH sufferers most often require one or more preventive drugs, the most effective being steroids (oral or as suboccipital infiltrations), verapamil, lithium carbonate, and methysergide. Unfortunately, about 1% of CCH patients become refractory to all existing pharmacological treatments.

Criteria defining (pharmacologically) intractable chronic cluster headache (iCCH) as well as intractable chronic migraine were recently proposed (Goadsby et al., 2006). Intractable CCH ruins the patients' social, family, and professional life, and may push some of them to commit suicide. Hence, various invasive lesional procedures have been tempted in recent decades, targeting the trigeminal or cranial parasympathetic pathways. Examples include radiofrequency lesions, glycerol injections or balloon compressions of the gasserian ganglion, gamma knife surgery or root section of the trigeminal nerve, trigeminal tractotomy, lesions of the nervus intermedius or greater superficial petrosal nerve, blockade or radiofrequency lesions of the pterygopalatine ganglion, and microvascular decompression of the trigeminal nerve combined with nervus intermedius section (Matharu et al., 2003). None of these sometimes lesional procedures gave satisfactory results in the long term.

More recently, neurostimulation therapy has raised new hope for iCCH patients. In this review, we will summarize the available data for hypothalamic deep-brain stimulation (hDBS) and ONS. These published data are summarized in Table 37.1.