Lessons from 8 years' experience of hypothalamic stimulation in cluster headache

Neuroimaging studies in cluster headache (CH) patients have increased understanding of attack-associated events and provided clues to the pathophysiology of the condition. They have also suggested stimulation of the ipsilateral posterior inferior hypothalamus as a treatment for chronic intractable CH. After 8 years of experience, stimulation has proved successful in controlling the pain attacks in almost 60% of chronic CH patients implanted at various centres. Although hypothalamic implant is not without risks, it has generally been performed safely. Implantation affords an opportunity to perform microrecordings of individual posterior hypothalamic neurons. These studies are at an early stage, but suggest the possibility of identifying precisely the target site by its electrophysiological characteristics. Autonomic studies of patients undergoing posterior hypothalamic stimulation provide further evidence that long-term stimulation is safe, revealing that it can cause altered modulation of the mechanisms of orthostatic adaptation without affecting the baroreflex, cardiorespiratory interactions or efferent sympathetic and vagal functions. Chronically stimulated patients have an increased threshold for cold pain at the site of the first trigeminal branch ipsilateral to the stimulated side; when the stimulator is switched off, changes in sensory and pain thresholds do not occur immediately, suggesting that long-term stimulation is required to induce sensory and nociceptive changes. Posterior inferior hypothalamic stimulation is now established as a treatment for many chronic CH patients. The technique is shedding further light on the pathophysiology of the disease, and is also providing clues to functioning of the hypothalamus itself.     

Hypothalamic deep brain stimulation for cluster headache: experience from a new multicase series

Deep brain stimulation (DBS) of the posterior hypothalamus was found to be effective in the treatment of drug-resistant chronic cluster headache. We report the results of a multicentre case series of six patients with chronic cluster headache in whom a DBS in the posterior hypothalamus was performed. Electrodes were implanted stereotactically in the ipsilateral posterior hypothalamus according to published coordinates 2 mm lateral, 3 mm posterior and 5 mm inferior referenced to the mid-AC-PC line. Microelectrode recordings at the target revealed single unit activity with a mean discharge rate of 17 Hz (range 13–35 Hz, n  = 4). Out of six patients, four showed a profound decrease of their attack frequency and pain intensity on the visual analogue scale during the first 6 months. Of these, one patient was attack free for 6 months under neurostimulation before returning to the baseline which led to abortion of the DBS. Two patients had experienced only a marginal, non-significant decrease within the first weeks under neurostimulation before returning to their former attack frequency. After a mean follow-up of 17 months, three patients are almost completely attack free, whereas three patients can be considered as treatment failures. The stimulation was well tolerated and stimulation-related side-effects were not observed on long term. DBS of the posterior inferior hypothalamus is an effective therapeutic option in a subset of patients. Future controlled multicentre trials will need to confirm this open-label experience and should help to better define predictive factors for non-responders.     

Success,failure, and putative mechanisms in hypothalamic stimulation for drug-resistant chronic cluster headache

Drug-resistant chronic cluster headache (CH) is an unremitting illness with excruciatingly severe headaches that occur several times daily. Starting in 2000, a total of 19 patients with long-lasting chronic CH, with multiple daily attacks unresponsive to all known prophylactics, received stimulation of the posterior inferior hypothalamic area ipsilateral to the pain as treatment. We report long-term follow-up (median 8.7 years, range 6–12 years) in 17 patients. Long-lasting improvement occurred in 70% (12 of 17): 6 are persistently almost pain-free; another 6 no longer experience daily attacks but rather episodic CH interspersed with long-lasting remissions. In 5 of 6 almost pain-free patients, the stimulators have been off for a median of 3 years (range 3–4 years). Five patients did not improve: 4 had bilateral CH, and 3 developed tolerance after experiencing relief for 1–2 years. Adverse events are electrode displacement (n = 2), infection (electrode n = 3; generator n = 1), electrode malpositioning (n = 1), transient nonsymptomatic third ventricle hemorrhage (n = 1), persistent slight muscle weakness on one side (n = 1), and seizure (n = 1). This exceptionally long follow-up shows that hypothalamic stimulation for intractable chronic CH produces long-lasting improvement in many patients. Previous experience was limited to a median of 16 months. Important new findings are as follows: stimulation is well tolerated for many years after implantation; after several years during which stimulation was necessary for relief, a persistent almost pain-free condition can be maintained when stimulation is off, suggesting that hypothalamic stimulation can change disease course; tolerance can occur after marked long-lasting improvement; and bilateral chronic CH seems to predict poor response to hypothalamic stimulation.     

Effect on sleep of posterior hypothalamus stimulation in cluster headache

OBJECTIVE: To evaluate the structure and quality of sleep and the circadian rhythm of body core temperature (BcT degrees ) in patients with drug-resistant chronic cluster headache (CH) before and during deep brain stimulation (DBS) of the posterior hypothalamus. BACKGROUND: Chronic CH is a severe primary headache and frequently associated with disturbances in sleep. Posterior hypothalamus DBS is performed as an effective treatment of drug-resistant chronic CH. The effects of posterior hypothalamus DBS on sleep and the circadian rhythm of BcT degrees are unknown. METHODS: Three male patients with chronic drug-resistant CH underwent 48-hour consecutive polysomnography (PSG) by means of the VITAPORT system with determination of BcT degrees by means of a rectal probe. Recordings were done before electrode implantation in the posterior hypothalamus and after optimized DBS of posterior hypothalamus. RESULTS: Before electrode implantation PSG showed nocturnal CH attacks, reduced sleep efficiency, fragmented sleep and increased periodic limb movements in sleep (PLMS). During DBS nocturnal CH attacks were abolished and sleep efficiency and PLMS improved. BcT degrees circadian rhythm was normal both before and during DBS. CONCLUSIONS: Our data show that DBS of posterior hypothalamus in drug-resistant chronic CH is effective in curtailing nocturnal CH attacks, and is associated with improved sleep structure and quality. Chronic CH displays a normal circadian rhythm of BcT degrees, unchanged during hypothalamic DBS.     

A review of hormonal findings in cluster headache. Evidence for hypothalamic involvement

The cause of cluster headache remains to be determined. The involvement of peripheral neurovascular structures can explain the pain and autonomic signs of a cluster attack, but not its rhythmicity. The central theory of cluster headache attributes the cyclic recurrence to involvement of the hypothalamus. To evaluate hypothalamic dysfunction a number of hormone studies have been carried out on cluster headache patients. Alterations in plasma melatonin, cortisol, testosterone, gonadotrophins, prolactin, growth hormone and thyrotropin have been documented, some only in the cluster period but others in the remission phase of the illness. We believe that the hormonal abnormalities in cluster headache support disorders of hypothalamic function.     

Sustained effectiveness of occipital nerve stimulation in drug-resistant chronic cluster headache

(Headache 2011;51:1191‐1201) Background.— Drug‐resistant chronic cluster headache (drCCH) is a devastating condition for which various invasive therapeutic procedures have been tempted without any satisfactory effect. Recent studies suggest that occipital nerve stimulation (ONS) could be an efficient preventive treatment of drCCH. Objective.— We conducted a prospective pilot trial of ONS in 8 subjects suffering from drCCH with encouraging results at 15 months. However, studies on a larger population with a longest follow‐up were warranted. Methods.— We recruited 15 patients with drCCH according to the previously published criteria of intractability. They were implanted with suboccipital stimulators on the side of their headache. Long‐term follow‐up was achieved by questionnaires administered during a headache consultation and/or by phone interviews. Results.— Mean follow‐up time post surgery is 36.82 months (range 11‐64 months). One patient had an immediate post‐operative infection of the material. Among the 14 remaining patients, 11 (ie, ～80%) have at least a 90% improvement with 60% becoming pain‐free for prolonged periods. Two patients did not respond or described mild improvement. Intensity of residual attacks is not modified by ONS. Four patients (29%) were able to reduce their prophylaxis. The major technical problems were battery depletion due to the use of high current intensities (N = 9/14, 64%) and immediate or delayed material infection (N = 3/15, 20%). Significant electrode migration was only seen in 1 patient. Clinical peculiarities during the ONS follow‐up period were side shift with infrequent contralateral attacks (N = 5/14, 36%), and/or isolated ipsilateral autonomic attacks without pain (N = 5/14, 36%). Two patients found ONS‐related paresthesias unbearable: one had his stimulator removed, and the other switched it off although he was objectively ameliorated. Subjectively, 9 patients are very satisfied by ONS and 3 patients moderately satisfied. Effective stimulation parameters varied between patients. Conclusions.— Our long‐term follow‐up confirms the efficacy of ONS in drCCH, which remains a safe and well‐tolerated technique. The occurrence of contralateral attacks and isolated autonomic attacks in nearly 50% of ONS responders may have therapeutic and pathophysiological implications.     

Unilateral impairment of pupillary response to trigeminal nerve stimulation in cluster headache

The pupillary constriction induced ipsilaterally by transcutaneous electrical nerve stimulation (TENS) of the infratrochlear nerve was measured, using an electronic pupillometer, in 26 episodic cluster headache (CH) and 15 migraine sufferers tested during an attack-free period and in 16 healthy controls. In controls, TENS gave rise to a miosis which was slow in onset and long-lasting in duration, and which was comparable to that mediated by tachykinins in animals. A similar miotic response was bilaterally observed in migraine patients and in CH patients examined during the inactive phase. In CH sufferers during the cluster period, TENS only elicited a normal pupillary constriction in the asymptomatic eye, whereas the resulting response in the symptomatic eye was markedly decreased. Although the exact mechanism underlying the dysfunction remains to be clarified, these results seem to indicate that ocular trigeminal pathways are involved in CH.