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

Abstract

Chronic cluster headache (CCH) is a disabling primary headache, considering the severity and frequency of pain attacks. Deep brain stimulation (DBS) has been used to treat severe refractory CCH, but assessment of its efficacy has been limited to open studies. We performed a prospective crossover, double-blind, multicenter study assessing the efficacy and safety of unilateral hypothalamic DBS in 11 patients with severe refractory CCH. The randomized phase compared active and sham stimulation during 1-month periods, and was followed by a 1-year open phase. The severity of CCH was assessed by the weekly attacks frequency (primary outcome), pain intensity, sumatriptan injections, emotional impact (HAD) and quality of life (SF12). Tolerance was assessed by active surveillance of behavior, homeostatic and hormonal functions. During the randomized phase, no significant change in primary and secondary outcome measures was observed between active and sham stimulation. At the end of the open phase, 6/11 responded to the chronic stimulation (weekly frequency of attacks decrease >50%), including three pain-free patients. There were three serious adverse events, including subcutaneous infection, transient loss of consciousness and micturition syncopes. No significant change in hormonal functions or electrolytic balance was observed. Randomized phase findings of this study did not support the efficacy of DBS in refractory CCH, but open phase findings suggested long-term efficacy in more than 50% patients, confirming previous data, without high morbidity. Discrepancy between these findings justifies additional controlled studies (clinicaltrials.gov number NCT00662935).

MRI atlas of the human hypothalamus

“…Finally, the dorsomedial hypothalamic nucleus, which may constitute an important neural relay in the central regulation of homeostasis in humans (Dai et al, 1998;Elias et al, 2001;Koutcherov et al, 2004), as it is known to be in rodents (Bellinger and Bernardis, 2002;Thompson and Swanson, 2003), can also be spotted using the T13D MRI sequences. The target for deep brain stimulation in the treatment of chronic cluster headaches, i.e., the posterior hypothalamic area (Leone et al, 2001;Fontaine et al, 2010;Franzini et al, 2010), is also clearly identifiable using high-resolution T13D sequences in 1.5T MRI.…”

“…Functional stereotactic neurosurgery of the hypothalamus is currently used for the treatment of cluster headaches (Leone et al, 2001;Fontaine et al, 2010;Franzini et al, 2010), and has recently been shown to have beneficial effects in the treatment of paroxysmal ophthalmic pain in multiple sclerosis patients (Cordella et al, 2009). Excitingly, it has also been shown to activate neural activity in cognitive and memory circuits in patients with mild Alzheimer's disease (Laxton et al).…”

Surgical Interventions for Cluster Headache, Including Implanted Stimulators

“…There has been considerable progress in neurostimulation approaches, both central and peripheral, in the treatment of primary headache disorders, including chronic CH ( Infection, transient loss of consciousness, micturition syncopes, transient ischemic attack, asymptomatic third ventricular hemorrhage, panick attack and even death due to intracerebral haemorrhage along the lead tract have been reported (Franzini et al 2003;Schoenen et al 2005;Fontaine et al 2010). Many authors advocate the use of ONS prior to hypothalamic DBS when considering a neuromodulation procedure (Ambrosini 2007;Leone et al 2008;Bartsch et al 2009;Burns et al 2009).…”

Stimulation of the sphenopalatine ganglion in intractable cluster headache: Expert consensus on patient selection and standards of care

“…For these patients, invasive (such as deep brain stimulation of the posterior hypothalamus, occipital nerve stimulation and vagal nerve stimulation) and non-invasive neuromodulatory approaches (such as transcutaneous supraorbital nerve stimulation, transcranial direct current stimulation, transcutaneous vagal nerve stimulation and transcranial magnetic stimulation) are increasingly considered in chronic cluster headache (5)(6)(7). Although no significant difference between active stimulation with preset parameters over a period of 4 weeks compared with no stimulation could be found in the only randomized controlled cross-over trial on deep brain stimulation of the posterior hypothalamic area (8), data from the subsequent open label period along with data from open label studies and case series (8)(9)(10)(11)(12)(13)(14) have shown response rates (defined as 50% reduction of attacks) of 50% and more in chronic cluster headache. Similar response rates have been reported in open label studies of occipital nerve stimulation (15)(16)(17)(18)(19), whereas anecdotal reports do not allow reliable assessment of the efficacy of vagal nerve stimulation (20), high cervical spinal cord stimulation (21) and various non-invasive approaches (see (6,7) for further review).…”