Alberto Proietti Cecchini

Long-term occipital nerve stimulation for drug-resistant chronic cluster headache.

Introduction Chronic cluster headache is rare and some of these patients become drug-resistant. Occipital nerve stimulation has been successfully employed in open studies to treat chronic drug-resistant cluster headache. Data from large group of occipital nerve stimulation-treated chronic cluster headache patients with long duration follow-up are advantageous. Patients and methods Efficacy of occipital nerve stimulation has been evaluated in an experimental monocentric open-label study including 35 chronic drug-resistant cluster headache patients (mean age 42 years; 30 men; mean illness duration: 6.7 years). The primary end-point was a reduction in number of daily attacks. Results After a median follow-up of 6.1 years (range 1.6–10.7), 20 (66.7%) patients were responders (≥50% reduction in headache number per day): 12 (40%) responders showed a stable condition characterized by sporadic attacks, five responders had a 60–80% reduction in headache number per day and in the remaining three responders chronic cluster headache was transformed in episodic cluster headache. Ten (33.3%) patients were non-responders; half of these have been responders for a long period (mean 14.6 months; range 2–48 months). Battery depletion (21 patients 70%) and electrode migration (six patients – 20%) were the most frequent adverse events. Conclusions Occipital nerve stimulation efficacy is confirmed in chronic drug-resistant cluster headaches even after an exceptional long-term follow-up. Tolerance can occur years after improvement.

Advances in the understanding of cluster headache.

ABSTRACT Introduction: Cluster headache is the worst primary headache form; it occurs in paroxysmal excruciatingly severe unilateral head pain attacks usually grouped in cluster periods. The familial occurrence of the disease indicates a genetic component but a gene abnormality is yet to be disclosed. Activation of trigeminal afferents and cranial parasympathetic efferents, the so-called trigemino-parasympathetic reflex, can explain pain and accompanying oculo-facial autonomic phenomena. In particular, pain in cluster headache is attributed, at least in part, to the increased CGRP plasma levels released by activated trigeminal system. Posterior hypothalamus was hypothesized to be the cluster generator activating the trigemino-parasympathetic reflex. Efficacy of monoclonal antibodies against CRGP is under investigation in randomized clinical trials. Areas covered: This paper will focus on main findings contributing to consider cluster headache as a neurovascular disorder with an origin from within the brain. Expert commentary: Accumulated evidence with hypothalamic stimulation in cluster headache patients indicate that posterior hypothalamus terminates rather than triggers the attacks. More extensive studies on the genetics of cluster headache are necessary to disclose anomalies behind the increased familial risk of the disease. Results from ongoing clinical trials in cluster headache sufferers using monoclonal antibodies against CGRP will open soon a new era.

Central and Peripheral Neural Targets for Neurostimulation of Chronic Headaches

Purpose of ReviewChronic headache sufferers are estimated to be around 3% of the population. These patients have a high disease burden. When prophylactic treatments have low efficacy and tolerability, patients are in need of alternative therapeutic strategies and options.Recent FindingsIn the last decade, a number of neuromodulation procedures have been introduced as treatment of chronic intractable headache patients when pharmacological treatments fail or are not well tolerated. Neurostimulation of peripheral and central nervous system has been carried out, and now, various non-invasive and invasive stimulation devices are available. Non-invasive neurostimulation options include vagus nerve stimulation, supraorbital stimulation and single-pulse transcranial magnetic stimulation; invasive procedures include occipital nerve stimulation, sphenopalatine ganglion stimulation and hypothalamic deep brain stimulation. In many cases, results supporting their use derive from open-label series and small controlled trial studies. Lack of adequate placebo hampers adequate randomized controlled trials.SummaryIn this paper, we give an overview on the main neurostimulation procedures in terms of results and putative mechanism of cation.

Defective functional connectivity between posterior hypothalamus and regions of the diencephalic-mesencephalic junction in chronic cluster headache:

Objective We tested the hypothesis of a defective functional connectivity between the posterior hypothalamus and diencephalic-mesencephalic regions in chronic cluster headache based on: a) clinical and neuro-endocrinological findings in cluster headache patients; b) neuroimaging findings during cluster headache attacks; c) neuroimaging findings in drug-refractory chronic cluster headache patients improved after successful deep brain stimulation. Methods Resting state functional magnetic resonance imaging, associated with a seed-based approach, was employed to investigate the functional connectivity of the posterior hypothalamus in chronic cluster headache patients (n = 17) compared to age and sex-matched healthy subjects (n = 16). Random-effect analyses were performed to study differences between patients and controls in ipsilateral and contralateral-to-the-pain posterior hypothalamus functional connectivity. Results Cluster headache patients showed an increased functional connectivity between the ipsilateral posterior hypothalamus and a number of diencephalic-mesencephalic structures, comprising ventral tegmental area, dorsal nuclei of raphe, and bilateral substantia nigra, sub-thalamic nucleus, and red nucleus (p < 0.005 FDR-corrected vs. control group). No difference between patients and controls was found comparing the contralateral hypothalami. Conclusions The observed deranged functional connectivity between the posterior ipsilateral hypothalamus and diencephalic-mesencephalic regions in chronic cluster headache patients mainly involves structures that are part of (i.e. ventral tegmental area, substantia nigra) or modulate (dorsal nuclei of raphe, sub-thalamic nucleus) the midbrain dopaminergic systems. The midbrain dopaminergic systems could play a role in cluster headache pathophysiology and in particular in the chronicization process. Future studies are needed to better clarify if this finding is specific to cluster headache or if it represents an unspecific response to chronic pain.

ONS and DBS for the Treatment of Chronic Cluster Headache

Research focus: Chronic cluster headache (CCH) is a pathological entity leading to a severe degree of disability. It is characterized by pain attacks occurring daily or spaced out by remission periods of <1 month, contrarily to the episodic form. When the condition results to be refractory to conservative treatments (both prophylactic and abortive treatments) and when such condition is present for at least 2 years, surgical treatment is suggested. Research methods: We here report our institutional experience with regard to both occipital nerve stimulation (ONS) and deep brain stimulation (DBS) for the treatment of the disease. Results/findings of the research: 15 out of 28 (65%) patients submitted to ONS had ≥50% reduction in 32 headache number per day and were considered responders; 12 out of 17 patients (70%) submitted to phyp DBS showed long-last improvement. Main conclusions and recommendations: Although no valid predictive factor is available at the moment, due to the lack of prospective and randomized studies, both procedures seem to constitute safe and valid treatments for such disabling condition.