Commentary on Fontaine et al.: Safety and efficacy of deep brain stimulation in refractory cluster headache: a randomized placebo-controlled double-blind trial followed by a 1-year open extension

摘要

Among primary headaches, cluster headache is certainly the most painful and unbearable, particularly for the patients suffering from its chronic form. It is characterized by attacks of unilateral periorbital, frontal and/or temporal pain associated with ipsilateral autonomic signs (ptosis, miosis, conjunctival injection, tearing, rhinorrhoea, nasal congestion). Its episodic form is characterized by bouts (clusters) of weeks or months, separated by headache-free intervals of variable length (months or years), but in chronic cluster headache (CCH), which affects almost 10% of patients, the attacks persist for at least 1year without remission, or with remissions lasting less than 1month [1]. These patients often require one or more preventive drugs for relief, such as steroids, verapamil, lithium carbonate and methysergide. Unfortunately, about 1% of CCH patients become refractory to all existing pharmacological treatments. In fact, suffering from intractable CCH is an atrocious condition, which affects every aspect of the patients鈥?lives, and may even push some of them to commit suicide as the ultimate desperate solution to avoid pain. Thus, it is imperative for headache clinicians and researchers, to test any possible remedy to this condition by invasive and non-invasive surgical procedures when pharmacological remedies have failed. Over the years, many such procedures have been used, such as 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 [2]; none of these have displayed satisfactory long-term results. In addition, when neuromodulation methods were first applied with success in some cases of intractable CCH [3], they immediately had a great resonance in the scientific community and aroused great hope in affected patients. The neuromodulation techniques used up to now are deep brain stimulation (DBS) of the ventro-posterior hypothalamus [3鈥?span class="CitationRef">6] and occipital nerve stimulation [7, 8]. Observational studies of hypothalamic DBS (hBDS) seemed to report slightly better results, but also more serious side effects, culminating in fatal cerebral haemorrhage in one patient. Because of this potential risk of hDBS procedures, it is of uttermost importance to carefully select CCH patients to whom hDBS will be proposed and to provide evidence-based proof of its clinical efficacy. Criteria defining drug-resistant chronic cluster headache (iCCH) patients are based on experts鈥?opinion and widely accepted [9, 10]. The consensus is that patients cannot be considered drug-resistant unless drugs known to be effective in cluster headache and belonging to at least three different pharmacological classes have been administered at a sufficient dose and for a sufficient time. In two studies [5, 6], attack recurrence at varying delays was described when the stimulator was switched off or when the battery ran flat, suggesting that the clinical effect was probably not due to the natural history of the disorder. Since the stimulation is not perceived by the patient, these observations also do not favour a placebo effect, although they cannot rule it out [11]. A placebo-controlled study was thus urgently needed, and Fontaine et al. deserve praise for organizing and completing such a trial embracing a substantial number of patients [12]. The study by Fontaine et al., the first controlled trial for hDBS in CCH, was a multicenter double-blind study conducted on 11 patients, who after the electrode implantation were randomized to a 鈥渟witch on鈥?or a 鈥渟witch off鈥?condition [12]. This 鈥渞andomized phase鈥?consisted in a cross-over trial, where in the first month, a group of patie