Functional connectivity of hypothalamus in chronic migraine with medication overuse.

OBJECTIVE: To investigate the functional connectivity of the hypothalamus in chronic migraine compared to interictal episodic migraine in order to improve our understanding of migraine chronification. METHODS: Using task-free fMRI and ROI-to-ROI analysis, we compared anterior hypothalamus intrinsic connectivity with the spinal trigeminal nucleus in patients with chronic migraine (n = 25) to age- and sex-matched patients with episodic migraine in the interictal phase (n = 22). We also conducted a seed-to-voxel analysis with anterior hypothalamus as a seed. RESULTS: All patients with chronic migraine had medication overuse. We found a significant connectivity (T = 2.08, p = 0.024) between anterior hypothalamus and spinal trigeminal nucleus in the chronic group, whereas these two regions were not connected in the episodic group. The strength of connectivity was not correlated with pain intensity (rho: 0.09, p = 0.655). In the seed-to-voxel analysis, three regions were more connected with the anterior hypothalamus in the chronic group: The spinal trigeminal nuclei (MNI coordinate x = 2, y = -44, z = -62), the right dorsal anterior insula (MNI coordinate x = 10, y = 10, z = 18), and the right caudate (MNI coordinate x = 12, y = 28, z = 6). However, these correlations were no longer significant after whole brain FWE correction. CONCLUSION: An increased functional connectivity between the anterior hypothalamus and the spinal trigeminal nucleus, as previously reported in preictal episodic migraine, was demonstrated in chronic migraine with medication overuse. This finding confirms a major role of the anterior hypothalamus in migraine and suggests that chronic migraineurs are locked in the preictal phase.

Treatment of refractory chronic cluster headache by chronic occipital nerve stimulation.

BACKGROUND: Greater occipital nerve stimulation (ONS) has been recently proposed to treat severe chronic cluster headache patients (CCH) refractory to medical treatment. We report the results of a French multidisciplinary cohort study. METHODS: Thirteen CCH patients were operated and data were collected prospectively. All of them suffered from CCH according to the International Headache Society classification, lasting for more than 2 years, refractory to pharmacological prophylactic treatment with adequate trials, with at least one daily attack. Chronic ONS was delivered through a subcutaneous occipital electrode connected to an implanted generator, in order to induce paraesthesias perceived locally in the lower occipital region. RESULTS: After surgery (mean follow-up 14,6 months), the mean attack frequency and intensity decreased by 68% and 49%, respectively. At last follow-up, 10/13 patients were considered as responders (improvement >50%). Prophylactic treatment could be stopped or reduced in 8/13 cases. Local infection occurred in one patient, leading to hardware removal. CONCLUSIONS: Our data confirmed the results of the 36 similar cases reported in the literature, suggesting that ONS may act as a prophylactic treatment in chronic CH. Considering their respective risks, ONS should be proposed before deep brain stimulation in severe refractory CCH patients.

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.

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).

Hypothalamic activation in spontaneous migraine attacks.

BACKGROUND: Migraine sufferers experience premonitory symptoms which suggest that primary hypothalamic dysfunction is a likely trigger of the attacks. Neuroendocrine and laboratory data also support this hypothesis. To date, positron emission tomography (PET) scans of migraine sufferers have demonstrated activation of brainstem nuclei, but not of the hypothalamus. OBJECTIVE: To record cerebral activations withH2 15OPET during spontaneous migraine without aura attacks. METHODS: We scanned 7 patients with migraine without aura (6 females and 1 male) in each of 3 situations: within 4 hours of headache onset, after headache relief by sumatriptan injection (between the fourth and the sixth hour after headache onset), and during an attack-free period. RESULTS: During the headache we found not only significant activations in the midbrain and pons, but also in the hypothalamus, all persisting after headache relief by sumatriptan. CONCLUSION: Hypothalamic activity, long suspected by clinical and experimental arguments as a possible trigger for migraine, is demonstrated for the first time during spontaneous attacks.