Commentary on Fontaine et al.: "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".

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Identifying a gene expression signature of cluster headache in blood

Cluster headache is a relatively rare headache disorder, typically characterized by multiple daily, short-lasting attacks of excruciating, unilateral (peri-)orbital or temporal pain associated with autonomic symptoms and restlessness. To better understand the pathophysiology of cluster headache, we used RNA sequencing to identify differentially expressed genes and pathways in whole blood of patients with episodic (n = 19) or chronic (n = 20) cluster headache in comparison with headache-free controls (n = 20). Gene expression data were analysed by gene and by module of co-expressed genes with particular attention to previously implicated disease pathways including hypocretin dysregulation. Only moderate gene expression differences were identified and no associations were found with previously reported pathogenic mechanisms. At the level of functional gene sets, associations were observed for genes involved in several brain-related mechanisms such as GABA receptor function and voltage-gated channels. In addition, genes and modules of co-expressed genes showed a role for intracellular signalling cascades, mitochondria and inflammation. Although larger study samples may be required to identify the full range of involved pathways, these results indicate a role for mitochondria, intracellular signalling and inflammation in cluster headach

Surgical Interventions for Cluster Headache, Including Implanted Stimulators

Migraine is an episodic painful disorder which can gradually chronify, and is among the most common neurological diseases in clinical practice. Such process is often accompanied by the appearance of acute drugs overuse. Chronic migraine (CM) constitutes migraine’s natural evolution in its chronic form and involves headache frequency of 15 days/month, with features similar to those of migraine attacks. Migraine given by drugs overuse, defined by ICDH-II in 2004 (and revised in 2005) as MOH, represents a common and debilitating disorder, which can be defined as generation, perpetuation and persistence of intense chronicmigraine caused by the frequent and excessive use of (symptomatic) drugs for at least 3 months, for a certain number of days permonth, giving an immediate relief. Migraine’s progression from an episodic to a chronic form is generally influenced by baseline headache frequency, inappropriate use of rescue selfmedication, absence of referral to headache centers during the worsening period in terms of headache days frequency, as well as by lack of education in avoiding trigger factors or inadequate lifestyle rhythms (fasting, sleepiness). In MOH sufferers, the only treatment of choice is represented by drug withdrawal. Successful detoxification is necessary to ensure improvement in the headache status when treating patients who overuse acute medications. Possible therapeutic agents in CM re-prophylaxis after detoxification are OnabotulinumtoxinA and Topiramate. The future in relapse prevention of CM complicated by MOH consists in considering how drugs currently used, such as triptans and emerging therapies, present responsivity profiles related to well-defined genetic polymorphisms