Gennaro Bussone

Stereotactic stimulation of posterior hypothalamic gray matter in a patient with intractable cluster headache.

To the Editor: Cluster headache is the most severe form of primary headache.1 Positron-emission tomography has shown activation of the homolateral posterior inferior hypothalamic gray matter during...

Specific hypothalamic activation during a spontaneous cluster headache attack

Cluster headache, the most severe pain condition among the primary headache syndromes, is characterized by unilateral excruciating head pain and autonomic dysfunction.1 Functional neuroimaging has recently improved the pathophysiologic understanding of the different primary headache syndromes. Thereby, brainstem activation was found in migraine,2,3⇓ and hypothalamic overactivity was observed in nitrate-induced cluster headache4 and in short-lasting, unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT).5 Results of voxel-based morphometry support the role of the posterior hypothalamus in the pathogenesis of cluster headache because an increased gray matter density has been shown in this structure.6 However, the cluster headache attacks investigated so far were triggered with nitroglycerin (NTG). Although clinical and experimental data show NTG-provoked and spontaneous cluster attacks to be comparable and NTG does not alter regional cerebral blood flow (rCBF) significantly,4 the vasoactive properties of nitrates have to be considered, and data from spontaneous cluster attacks are desirable to confirm the mentioned results. We present a case of a spontaneous cluster attack during an ongoing H215O-PET study. A man (aged 30 years, right-handed, no medication) with a 2-year history of chronic cluster headache …

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.

Deep Brain Stimulation for Intractable Chronic Cluster Headache: Proposals for Patient Selection:

Cluster headache is the most severe of the primary headaches. Positron emission tomography and functional MRI studies have shown that the ipsilateral posterior hypothalamus is activated during cluster headache attacks and is structurally asymmetric in these patients. These changes are highly specific for the condition and suggest that the cluster headache generator may be located in that brain area; they further suggest that electrical stimulation of that region might produce clinical improvement in chronic cluster headache sufferers refractory to medical therapy. In five patients with severe intractable chronic cluster headache, hypothalamic electrical stimulation produced complete and long-term pain relief with no relevant side-effects. We therefore consider it essential to propose criteria for selecting chronic cluster headache patients for hypothalamic deep brain stimulation before this procedure is undertaken at other academic medical centres.

Double blind comparison of lithium and verapamil in cluster headache prophylaxis

SYNOPSIS

Plasma Cytokine Levels in Migraineurs and Controls

Background.—The vasoactive peptide, calcitonin gene‐related peptide (CGRP), is released from primary afferent neurons in the trigemino‐vascular circulation during migraine headache. CGRP at physiological concentrations and possibly via stimulation of its selective receptors on T‐cells, triggers the secretion of cytokines. Cytokines play an important role in several physiological and pathological settings such as immunology, inflammation, and pain.

Deep brain stimulation to relieve drug-resistant SUNCT

The rare primary headache short‐lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is characterized by 3 to 200 attacks per day of severe unilateral orbital pain. Functional magnetic resonance imaging shows increased blood flow in the ipsilateral posterior inferior hypothalamus during attacks, indicating activation. We report the first patient with SUNCT in whom severe intractable pain (70 per day) was well controlled by electrode implant to and continuous stimulation of the posterior inferior hypothalamus. Ann Neurol 2005;57:925–927

Behavioral and pharmacologic treatment of transformed migraine with analgesic overuse: Outcome at 3 years

Objective.—To determine whether combined treatment using medication and biofeedback would be more effective than drug treatment alone for treating transformed migraine complicated by analgesic overuse.

Verapamil in the prophylaxis of episodic cluster headache: A double-blind study versus placebo

Article abstract The authors performed a double-blind, double-dummy study to compare the efficacy of verapamil with placebo in the prophylaxis of episodic cluster headache. After 5 days’ run-in, 15 patients received verapamil (120 mg tid) and 15 received placebo (tid) for 14 days. The authors found a significant reduction in attack frequency and abortive agents consumption in the verapamil group. Side effects were mild. These findings provide objective evidence for the effectiveness of verapamil in episodic cluster headache prophylaxis.

Hypothalamic Deep Brain Stimulation in Positron Emission Tomography

Recently, functional imaging data have underscored the crucial role the hypothalamus plays in cluster headache, one of the most severe forms of primary headache. This prompted the application of hypothalamic deep brain stimulation. Yet, it is not apparent how stimulation of an area that is thought to act as a pace-maker for acute headache attacks is able to prevent these attacks from occurring. We addressed this issue by examining 10 operated chronic cluster headache patients, using H215O-positron emission tomography and alternately switching the hypothalamic stimulator on and off. The stimulation induced activation in the ipsilateral hypothalamic gray (the site of the stimulator tip), the ipsilateral thalamus, somatosensory cortex and praecuneus, the anterior cingulate cortex, and the ipsilateral trigeminal nucleus and ganglion. We additionally observed deactivation in the middle temporal gyrus, posterior cingulate cortex, and contralateral anterior insula. Both activation and deactivation are situated in cerebral structures belonging to neuronal circuits usually activated in pain transmission and notably in acute cluster headache attacks. Our data argue against an unspecific antinociceptive effect or pure inhibition of hypothalamic activity. Instead, the data suggest a hitherto unrecognized functional modulation of the pain processing network as the mode of action of hypothalamic deep brain stimulation in cluster headache.