Cluster Headache Genomewide Association Study and Meta-Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor.

Objective: The objective of this study was to aggregate data for the first genomewide association study meta-analysis of cluster headache, to identify genetic risk variants, and gain biological insights.

Methods: A total of 4,777 cases (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from 10 European and 1 East Asian cohorts. We first performed an inverse-variance genomewide association meta-analysis of 4,043 cases and 21,729 controls of European ancestry.

Intra- and interindividual attack frequency variability of chronic cluster headache.

Background: The lack of knowledge about the intra- and interindividual attack frequency variability in chronic cluster headache complicates power and sample size calculations for baseline periods of trials, and consensus on their most optimal duration.

Methods: We analyzed the 12-week baseline of the ICON trial (occipital nerve stimulation in medically intractable chronic cluster headache) for: (i) weekly vs. instantaneous recording of attack frequency; (ii) intra-individual and seasonal variability of attack frequency; and (iii) the smallest number of weeks to obtain a reliable estimate of baseline attack frequency.

Safety and efficacy of occipital nerve stimulation for attack prevention in medically intractable chronic cluster headache (ICON): a randomised, double-blind, multicentre, phase 3, electrical dose-controlled trial.

Background: Occipital nerve stimulation (ONS) has shown promising results in small uncontrolled trials in patients with medically intractable chronic cluster headache (MICCH). We aimed to establish whether ONS could serve as an effective treatment for patients with MICCH.

Methods: The ONS in MICCH (ICON) study is an investigator-initiated, international, multicentre, randomised, double-blind, phase 3, electrical dose-controlled clinical trial.

Chronobiology and Sleep in Cluster Headache.

Background: Cluster headache attacks follow a striking circadian rhythm with an intriguing influence of sleep. We aim to investigate differences in sleep quality, chronotype, and the ability to alter individual sleep rhythms in episodic and chronic cluster headache patients vs controls.

Methods: Cluster headache patients and non-headache controls from the Dutch Leiden University Cluster headache neuro-Analysis program aged 18 and above completed web-based questionnaires in a cross-sectional study.

Increased use of illicit drugs in a Dutch cluster headache population.

Introduction: Many patients with cluster headache report use of illicit drugs. We systematically assessed the use of illicit drugs and their effects in a well-defined Dutch cluster headache population.

Methods: In this cross-sectional explorative study, 756 people with cluster headache received a questionnaire on lifetime use and perceived effects of illicit drugs.

Aura in Cluster Headache: A Cross-Sectional Study.

Background: Aura symptoms have been reported in up to 23% of cluster headache patients, but it is not known whether clinical characteristics are different in participants with and without aura.

Methods: Using validated web-based questionnaires we assessed the presence and characteristics of attack-related aura and other clinical features in 629 subjects available for analysis from an initial cohort of 756 cluster headache subjects. Participants who screened positive for aura were contacted by telephone for confirmation of the ICHD-III criteria for aura.

Allodynia in cluster headache.

Cutaneous allodynia is an established marker for central sensitization in migraine. There is debate whether cutaneous allodynia may also occur in cluster headache, another episodic headache disorder. Here, we examined the presence and severity of allodynia in a large well-defined nationwide population of people with cluster headache.

Symptomatic Trigeminal Autonomic Cephalalgias.

Trigeminal autonomic cephalalgias (TACs) are primary headache syndromes that share some clinical features such as a trigeminal distribution of the pain and accompanying ipsilateral autonomic symptoms. By definition, no underlying structural lesion for the phenotype is found. There are, however, many descriptions in the literature of patients with structural lesions causing symptoms that are indistinguishable from those of idiopathic TACs.

Cluster headache and the hypocretin receptor 2 reconsidered: a genetic association study and meta-analysis.

Background: Cluster headache is a severe neurological disorder with a complex genetic background. A missense single nucleotide polymorphism (rs2653349; p.Ile308Val) in the HCRTR2 gene that encodes the hypocretin receptor 2 is the only genetic factor that is reported to be associated with cluster headache in different studies.

Cluster-tic syndrome: a cross-sectional study of cluster headache patients.

Objective: To determine the prevalence and nature of trigeminal neuralgia in a large group of cluster headache patients.

Background: Cluster-tic syndrome is a rare headache syndrome in which trigeminal neuralgia and cluster headache co-occur. The existence of cluster-tic syndrome as a separate entity is questioned, and figures on prevalence of simultaneous existence of cluster headache and trigeminal neuralgia are not available.

Occipital nerve stimulation in medically intractable, chronic cluster headache. The ICON study: rationale and protocol of a randomised trial.

Background: About 10% of cluster headache patients have the chronic form. At least 10% of this chronic group is intractable to or cannot tolerate medical treatment. Open pilot studies suggest that occipital nerve stimulation (ONS) might offer effective prevention in these patients.

Stepwise web-based questionnaires for diagnosing cluster headache: LUCA and QATCH.

Background: Cluster headache (CH) is a primary headache disorder that is diagnosed based on the patient's history. For large-scale epidemiologic and genetic studies, a web-based, preferably short, questionnaire can be a feasible alternative to replace time-consuming clinical interviews.

Methods: Self-reported CH patients were enrolled via our research website.

Neuroimaging in trigeminal autonomic cephalgias: when, how, and of what?

Purpose Of Review: Trigeminal autonomic cephalgias (TACs) are characterized by frequent, short-lasting headache attacks with ipsilateral facial autonomic features. They include cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing. The pathogenesis of TACs is largely unknown, but many case reports in the literature suggest that TACs are secondary to structural lesions.