BackgroundClinical observations and results from recent studies support the use of non-invasive vagus nerve stimulation (nVNS) for treating cluster headache (CH) attacks. This study compared nVNS with a sham device for acute treatment in patients with episodic or chronic CH (eCH, cCH).MethodsAfter completing a 1-week run-in period, subjects were randomly assigned (1:1) to receive nVNS or sham therapy during a 2-week double-blind period. The primary efficacy endpoint was the proportion of all treated attacks that achieved pain-free status within 15 minutes after treatment initiation, without rescue treatment.ResultsThe Full Analysis Set comprised 48 nVNS-treated (14 eCH, 34 cCH) and 44 sham-treated (13 eCH, 31 cCH) subjects. For the primary endpoint, nVNS (14%) and sham (12%) treatments were not significantly different for the total cohort. In the eCH subgroup, nVNS (48%) was superior to sham (6%; p < 0.01). No significant differences between nVNS (5%) and sham (13%) were seen in the cCH subgroup.ConclusionsCombing both eCH and cCH patients, nVNS was no different to sham. For the treatment of CH attacks, nVNS was superior to sham therapy in eCH but not in cCH. These results confirm and extend previous findings regarding the efficacy, safety, and tolerability of nVNS for the acute treatment of eCH.

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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. Results were compared with age and sex-matched official data from the Dutch general population. Results Compared to the data from the general population, there were more illicit drug users in the cluster headache group (31.7% vs. 23.8%; p < 0.01). Reduction in attack frequency was reported by 56% (n = 22) of psilocybin mushroom, 60% (n = 3) of lysergic acid diethylamide and 50% (n = 2) of heroin users, and a decreased attack duration was reported by 46% (n = 18) of PSI, 50% (n = 2) of heroin and 36% (n = 8) of amphetamine users. Conclusion In the Netherlands, people with cluster headache use illicit drugs more often than the general population. The question remains whether this is due to an actual alleviatory effect, placebo response, conviction, or common pathophysiological background between cluster headache and addictive behaviours such as drug use.

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. In this article, we review the recent insights in symptomatic TACs by comparing and categorizing newly published cases. We confirm that symptomatic TACs can have typical phenotypes. It is of crucial importance to identify symptomatic TACs, as the underlying cause will influence treatment and outcome. Our update focuses on when a structural lesion should be sought.

Background Two randomized, double-blind, sham-controlled trials (ACT1, ACT2) evaluated non-invasive vagus nerve stimulation (nVNS) as acute treatment for cluster headache. We analyzed pooled ACT1/ACT2 data to increase statistical power and gain insight into the differential efficacy of nVNS in episodic and chronic cluster headache. Methods Data extracted from ACT1 and ACT2 were pooled using a fixed-effects model. Main outcome measures were the primary endpoints of each study. This was the proportion of participants whose first treated attack improved from moderate (2), severe (3), or very severe (4) pain intensity to mild (1) or nil (0) for ACT1 and the proportion of treated attacks whose pain intensity improved from 2–4 to 0 for ACT2. Results The pooled population included 225 participants (episodic: n = 112; chronic: n = 113) from ACT1 (n = 133) and ACT2 (n = 92) in the nVNS (n = 108) and sham (n = 117) groups. Interaction was shown between treatment group and cluster headache subtype ( p < 0.05). nVNS was superior to sham in episodic but not chronic cluster headache (both endpoints p < 0.01). Only four patients discontinued the studies due to adverse events. Conclusions nVNS is a well-tolerated and effective acute treatment for episodic cluster headache. Trial registration The studies were registered at clinicaltrials.gov (ACT1: NCT01792817; ACT2: NCT01958125).

BackgroundAura 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.MethodsUsing 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.ResultsTypical aura symptoms before or during cluster headache attacks were found in 44/629 participants (7.0%) mainly involving visual symptoms (61.4%). Except for lower alcohol consumption and higher prevalence of frontal pain in participants with aura, no differences in clinical characteristics were found compared with participants without aura.ConclusionAt least 7.0% of the participants with cluster headache in our large cohort reported typical aura symptoms, which most often involved visual symptoms. No major clinical differences were found between participants with and without aura.

We present the first description of long-lasting dysgeusia and hyposmia as a side effect of lithium therapy in cluster headache. Dysgeusia has only rarely been reported as a side effect of lithium in other conditions and hyposmia has not previously been reported. Physicians should be aware of this rare, but severe, side effect when prescribing lithium.

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. Results A total of 478 episodic, 147 chronic cluster headache patients and 367 controls participated. Chronic cluster headache patients had more often early chronotypes than controls, as measured by mid‐sleep phase (P = .021 adjusted B −15.85 minutes CI −29.30; −2.40). Compared to controls, chronic cluster headache participants were less able to alter their sleep rhythms (P < .001 adjusted B −1.65 CI −2.55; 0.74), while episodic cluster headache participants reported more difficulty in coping with reduced sleep (P = .025 adjusted B 0.75 CI 0.09; 1.40). Sleep quality was reduced in both types of cluster headache compared to controls (“poor sleepers”: 71.4% (105/147) in chronic and 48.3% (235/367) in episodic cluster headache vs 25.6% (94/367) in controls; both P < .001; episodic adjusted B −1.71 CI 0.10; 0.32; chronic adjusted B −0.93 CI 0.24; 0.65). Conclusion Sleep quality is decreased in both episodic and chronic cluster headache, most likely caused by cluster headache attacks that strike during the night. Episodic cluster headache patients report more difficulty in coping with reduced sleep, while chronic patients are less able to alter their sleep rhythm. Although not directly proven, cluster headache patients will likely benefit from a structured, regular daily schedule.