Investigating Vitamin D Receptor Genetic Markers in a Cluster Headache Meta-Analysis.

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.

Patients with cluster headache show signs of insomnia and sleep related stress: results from an actigraphy and self-assessed sleep study.

BACKGROUND: Cluster headache (CH) is a primary headache disorder which is characterized by circadian timing of headache attacks, usually at nighttime, in around two thirds of patients. Patients with CH often report sleep difficulties, though it is unknown whether this is a cause or a consequence of nightly headache attacks. OBJECTIVE: In this case-control study we have assessed sleep quality in study participants with CH in cluster bout respectively in remission, compared to a control group of neurologically healthy individuals to investigate the potential connection between sleep and CH. METHODS: Fifty study participants with CH and 42 controls were recruited for sleep assessment. Sleep was recorded using MotionWatch 8 actigraphs (CamNTech) for a period of two weeks. Study participants were instructed to wear the unit during rest and sleep and to fill out a sleep diary daily through the two-weeks period. RESULTS: Results from actigraphy recordings and sleep diaries suggested that patients with CH spend longer time in bed than controls (CH 8.1 hours vs. Controls 7.7 hours, p=0.03), but do not sleep more than controls (CH 6.7 hours vs. controls 6.5 hours, p=0.3). In addition, CH patients reported increased sleep latency (p=0.003), particularly during, but not restricted to, cluster bouts. Study participants with CH further reported higher levels of stress at bedtime (p=0.01), and they felt less well rested than controls (p=0.001). CONCLUSION: Our analysis suggests that sleep is negatively affected in CH both in cluster bout and in remission, manifesting in symptoms consistent with insomnia such as prolonged sleep latency and increased time in bed.

Use of Prescribed and Non-Prescribed Treatments for Cluster Headache in a Swedish Cohort.

BACKGROUND: Cluster headache (CH) is a debilitating condition, but current therapies leave CH patients in pain. The extent of this problem in Sweden is unknown. METHODS: An anonymized questionnaire was sent to 479 Swedish CH patients to investigate patterns and perceived effects of treatments. RESULTS: Three hundred fourteen answers were analyzed. The population was representative regarding age of onset and sex. Less than half (46%) were satisfied with their abortive treatments, 19% terminated functioning abortive treatments due to side effects. Additionally, 17% of chronic CH patients had not tried the first-line preventive drug verapamil. A small subset had tried illicit substances to treat their CH (0-8% depending on substance). Notably, psilocybin was reported effective as an abortive treatment by 100% (n = 8), and with some level of effect as a preventive treatment by 92% (n = 12). For verapamil, some level of preventive effect was reported among 68% (n = 85). CONCLUSIONS: Our descriptive data illustrate that many Swedish CH patients are undertreated, lack functional therapies, and experience side effects. Further studies are warranted to search for new treatment strategies as well as a revision of current treatment guidelines with the aim of reducing patient disease burden to the greatest extent possible.

Genetic and Phenotypic Profiling of Triptan Users in a Swedish Cluster Headache Cohort.

Up to 25% of individuals who live with cluster headache (CH), an extremely painful primary headache disorder, do not adequately respond to the first-line treatment, triptans. Studies have indicated that genetic variants can play a role in treatment response. Likewise, differences in clinical characteristics can give clues to mechanisms underlying triptan non-response. Our aim was to investigate five genetic variants previously implicated in triptan response and their relation to triptan usage in our Swedish CH cohort and to investigate potential distinctions in clinical characteristics. 545 CH patients were screened for the genetic variants rs1024905, rs6724624, rs4795541, rs5443, and rs2651899 with a case control design based on triptan usage. Analysis of clinical characteristics was based on self-reported questionnaire data from 893 patients. One genetic variant, rs1024905, was significantly associated with triptan non-usage in CH (Pc = 0.010). In addition, multi-allele effector analysis showed that individuals with a higher number of effector variants were less likely to use triptans (P = 0.007). Analysis of clinical characteristics showed that triptan users were more likely to have alcohol as a trigger (57.4% vs 43.4%, P = 0.002), have autonomic symptoms (95.1% vs 88.1%, P = 0.002), and be current smokers (27.0% vs 21.9%, P = 0.033) compared to non-users. These results support the hypothesis that genetic variants can play a role in triptan usage in CH and that patients with a typical CH phenotype are more likely to use triptans.

PER Gene Family Polymorphisms in Relation to Cluster Headache and Circadian Rhythm in Sweden.

The trigeminal autonomic cephalalgia, cluster headache (CH), is one of the most painful disorders known to man. One of the disorder's most striking features is the reported diurnal rhythmicity of the attacks. For a majority of patients, the headache attacks occur at approximately the same time every day. Genetic variants of genes involved in the circadian rhythm such as Period Circadian Regulator 1, 2, and 3 (PER1, 2 and 3) are hypothesized to have an effect on the rhythmicity of the attacks. Six PER1, 2 and 3 genetic markers; the indel rs57875989 and five single nucleotide polymorphisms (SNPs), rs2735611, rs2304672, rs934945, rs10462020, and rs228697, were genotyped, using TaqMan® or regular polymerase chain reaction (PCR), in a Swedish CH case control material. Logistic regression showed no association between CH and any of the six genetic variants; rs57875989, p = 0.523; rs2735611, p = 0.416; rs2304672, p = 0.732; rs934945, p = 0.907; rs10462020, p = 0.726; and rs228697, p = 0.717. Furthermore, no difference in allele frequency was found for patients reporting diurnal rhythmicity of attacks, nor were any of the variants linked to diurnal preference. The results of this study indicate no involvement of these PER genetic variants in CH or diurnal phenotype in Sweden.