Objective To determine whether patients with cluster headache have more sickness absence and disability pension days compared to matched references and possible associations with sociodemographic characteristics. Methods We performed a registry study of all patients who had received specialized health care for cluster headache (ICD-10 code G44.0) aged 16–64 years and living in Sweden in 2010 (n = 3,240; 34% women) and matched references from the total population (n = 16,200) regarding their sickness absence and disability pension days in 2010. Results Mean number of sickness absence days in 2010 was 16.13 (95% confidence interval, 14.05–18.20) among patients with cluster headache and 6.54 (5.97–7.11) among references. When combining sickness absence and disability pension days, patients with cluster headache had 63.15 (58.84–67.45) days, references 34.08 (32.59–35.57) days. Among patients, women had twice as many sickness absence days than men: 23.71 (19.36–28.06) vs 12.41 (10.19–14.63). When adding disability pension days, those numbers were 83.71 (75.57–91.84) vs 52.56 (47.62–57.51). Patients with cluster headache had significantly more sickness absence days in all ages compared to the reference group. Patients with elementary education had more sickness absence/disability pension days (85.88 [75.34–96.42]) compared to those with high school (64.89 [58.82–70.97]) and college/university (41.42 [34.70–48.15]) education. Conclusion This nationwide study shows that patients with cluster headache have significantly more sickness absence and disability pension days compared to matched references. Furthermore, among patients, women had more sickness absence and disability pension days than men.

Cluster headache is a severe primary headache characterized by extremely painful attacks of unilateral headache. Verapamil is commonly used as a prophylactic treatment with good effect. In order to search for new pathways involved in the pathophysiology of cluster headache, we analyzed genetic variants that were previously linked to verapamil response in migraine in a Swedish cluster headache case-control sample. We used TaqMan qPCR for genetic screening and performed a gene expression analysis on associated genes in patient-derived fibroblasts, and further investigated which reference genes were suitable for analysis in fibroblasts from cluster headache patients. We discovered a significant association between anoctamin 3, a gene encoding a calcium-activated ion channel, and cluster headache. The association was not dependent on verapamil treatment since the associated variant, rs1531394, was also overrepresented in patients not using verapamil. No difference was found in the anoctamin 3 gene expression between controls and patients. Also, we determined that TBP, IPO8 and PDHB were suitable reference genes in cluster headache fibroblasts. This finding is the first report of an association between a variant in a gene encoding an ion-channel and cluster headache, and the first significant genetic evidence of calcium involvement in cluster headache pathophysiology.

Background and Purpose: Randomized patent foramen ovale closure trials have used open-label end point ascertainment which increases the risk of bias and undermines confidence in the conclusions. The Gore REDUCE trial prospectively performed baseline and follow-up magnetic resonance imaging (MRIs) for all subjects providing an objective measure of the effectiveness of closure. Methods: We performed blinded evaluations of the presence, location, and volume of new infarct on diffusion-weighted imaging of recurrent clinical stroke or new infarct (>3 mm) on T2/fluid attenuated inversion recovery from baseline to follow-up MRI at 2 years, comparing closure to medical therapy alone. We also examined the effect of shunt size and the development of atrial fibrillation on infarct burden at follow-up. Results: At follow-up, new clinical stroke or silent MRI infarct occurred in 18/383 (4.7%) patients who underwent closure and 19/177 (10.7%) medication-only patients (relative risk, 0.44 [95% CI, 0.24–0.81], P =0.02). Clinical strokes were less common in closure patients compared with medically treated patients, 5 (1.3%) versus 12 (6.8%), P =0.001, while silent MRI infarcts were similar, 13 (3.4%) versus 7 (4.0%), P =0.81. There were no differences in number, volumes, and distribution of new infarct comparing closure patients to those treated with medication alone. There were also no differences of number, volumes, and distribution comparing silent infarcts to clinical strokes. Infarct burden was also similar for patients who developed atrial fibrillation and for those with large shunts. Conclusions: The REDUCE trial demonstrates that patent foramen ovale closure prevents recurrent brain infarction based on the objective outcome of new infarcts on MRI. Only clinical strokes were reduced by closure while silent infarctions were similar between study arms, and there were no differences in infarct volume or location comparing silent infarcts to clinical strokes. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00738894.

Cluster headache (CH), a primary neurovascular headache syndrome, is characterized by recurrent, unilateral, short-lasting attacks of excruciating pain in the temporal and/or orbital region. The pain is considered one of the most severe pain conditions known to humans. Compared with the general population, first-degree relatives of probands with CH have a significantly increased risk of the same disorder. However, there seems to be no clear mode of inheritance, suggesting that both genetic and environmental factors are of importance, with the pathophysiology being multifactorial. Despite the genetic influence of the disease, a low prevalence and small pedigrees complicate the feasibility of genetic studies. To date, only genetic studies with limited sample sizes have been performed, but results have indicated an association with the HCRTR2 gene, which is involved in the regulation of chronobiological rhythms. Collaborative multicenter studies on large clinically well-defined materials are needed to reach a better understanding of the complex genetic background of CH.

Patients diagnosed with the primary headache disorder known as cluster headache (CH) commonly report that their headache attacks occur in patterns of both circadian and seasonal rhythmicity. Vitamin D is essential for a variety of bodily functions and vitamin D levels are largely regulated by daylight exposure in connection with seasonal variation. For this Sweden-based study, the association between CH and three single-nucleotide polymorphisms in the vitamin D receptor gene, rs2228570, rs1544410, and rs731236, were investigated, as well as CH bouts and trigger factors in relation to seasonal and weather changes. Over 600 study participants with CH and 600 controls were genotyped for rs2228570, and genotyping results for rs1544410 and rs731236 were obtained from a previous genome-wide association study. The genotyping results were combined in a meta-analysis, with data from a Greek study. No significant association was found between rs2228570 and CH or the CH subtype in Sweden, nor did the meta-analysis show significant results for any of the three markers. The most common period of the year to experience CH bouts in Sweden was autumn, and conditions linked to weather or weather changes were also identified as potential triggers for CH bouts for a quarter of the responders who reported bout triggers. Though we cannot rule out vitamin D involvement in CH, this study does not indicate any connection between CH and the three vitamin D receptor gene markers.