Objective: To investigate whether conditions causing inflammatory activation are associated with increased risk of idiopathic intracranial hypertension. Methods: All newly diagnosed idiopathic intracranial hypertension patients (cases) in Sweden between 2000–2016 were identified using pre-determined algorithms (n = 902) and matched with five controls from the general population and five individuals with an obesity diagnosis (n = 4510) for age, sex, region, and vital status. National health registers provided information on infections, inflammatory disorders and dispensed medications. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals. Results: Compared to general population controls, the cases had fourfold increased odds of having an infection (odds ratio = 4.3, 95% confidence interval 3.3–5.6), and threefold increased odds of an inflammatory disorder the year prior to idiopathic intracranial hypertension diagnosis (odds ratio = 3.2, 95% confidence interval 2.4–4.3). Organ specific analyses showed that odds were increased for the study diseases in the respiratory organ, kidney organ and gastrointestinal tract, but not for female genital infections. Similar results were found when comparing idiopathic intracranial hypertension with obese controls though the odds ratios were of lower magnitude. Sub-analyses on exposure to anti-infectious and anti-inflammatory drugs confirmed the increased odds ratios for idiopathic intracranial hypertension patients. Conclusions: These findings suggest that major inflammatory activation may be a risk factor in idiopathic intracranial hypertension development.

Objective: The objective of this cross‐sectional study was to investigate the extent of perceived sleep disturbances in a cluster headache cohort, and to compare how sleep is perceived between participants in an active headache bout to participants in a headache‐free remission period.Background: Cluster headache is a primary headache disorder characterized by extremely painful headache attacks. These attacks commonly occur with a circadian rhythm, with a majority of patients experiencing nocturnal attacks. Sleep is affected in patients with cluster headache, but there are many uncertainties regarding the pathophysiological connection between cluster headache and sleep disturbances and to what extent sleep disturbances persist into remission.Methods: A digital survey was sent out to 701 individuals with cluster headache between January and May 2024. The survey contained questions regarding general health, clinical cluster headache phenotype, and questions from the Karolinska Sleep Questionnaire, the Insomnia Severity Index, and the Dysfunctional Beliefs and Attitudes about Sleep‐10. Scores extracted from each questionnaire were compared between study participants in an active bout versus study participants in remission, and study participants in short‐term remission (<5 years) versus long‐term remission (≥5 years).Results: Of the 381 individuals who answered the survey, 325 were included in the final analysis. Participants in an active cluster headache bout reported increased sleep disturbances on all measurements compared to participants in remission (insomnia severity: adjusted odds ratio [aOR] = 1.12 [95% confidence interval (CI), 1.07–1.17] p < 0.001; sleep quality: aOR = 0.67 [95% CI, 0.53–0.83] p < 0.001; daytime sleepiness: aOR = 0.59 [95% CI, 0.44–0.78] p < 0.001; and dysfunctional beliefs: aOR = 1.03 [95% CI, 1.01–1.04] p = 0.001). Of the participants in an active bout, 46.5% scored above the Insomnia Severity Index threshold indicating moderate to severe insomnia (≥15) and 43.7% were considered as having poor sleep quality (≤3 on the Sleep Quality Index extracted from the Karolinska Sleep Questionnaire). This is in comparison to 22.0% of participants in remission being above the moderate insomnia threshold and 22.0% considered having poor sleep quality. Participants in long‐term remission had better sleep scores overall compared to participants in short‐term remission (insomnia severity: aOR = 1.09 [95% CI, 1.03–1.16] p = 0.005; daytime sleepiness: aOR = 0.67 [95% CI, 0.42–1.02] p = 0.072; and dysfunctional beliefs: aOR = 1.03 [95% CI, 1.01–1.05] p = 0.006).Conclusion: Individuals with cluster headache have a large degree of sleep disturbances that are exacerbated during an active bout and not completely alleviated during remission. Future studies are needed to determine if this gradual change in sleep disturbances after an active bout is due to physiological changes, which slowly revert to baseline levels after an active bout or connected to persisting negative behavioral or cognitive associations between sleep and headache.

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Background/Hypothesis: Rates of tobacco usage are higher in individuals with cluster headache. Tobacco usage exposes the user to a large variety of toxic compounds, detrimental to health, including heavy metals. We hypothesise that exposure to heavy metals through tobacco usage will drive epigenetic alterations in individuals with cluster headache. To elucidate the extent of heavy metal exposure and global epigenetic alterations arising from tobacco products in relation to cluster headache we performed a case-control study, using DNA methylation, gene and protein expression analysis to evaluate markers for smoking, epigenetic modifications and heavy metal exposure. Methods: RNA was purified from collected blood samples from 16 cluster headache participants and 16 control participants, converted to cDNA, and RNA expression quantified via RT-qPCR. This was done by investigating genes relevant for nicotine exposure; nicotinic acetylcholine receptors (nAChRs), heavy metal exposure; metallothionein (MT) family, markers of liver and kidney damage (ALT, Alb and NGAL), epigenetic enzymes for DNA methylation (DNMTs) and demethylation (TETs), normalized to the housekeeping gene TBP. MT3 protein expression was quantified using an ELISA kit in cerebrospinal fluid from 13 cluster headache participants and 13 control participants. The methylation status of CpG-rich regions of long-interspersed nucleotide element-1 (LINE-1), in bisulfite converted DNA of 20 smoking individuals with cluster headache, 33 non-smoking individuals with cluster headache and 26 control participants, was quantified by pyrosequencing. Results: An increased RNA expression of nicotinic acetylcholine receptor subunits CHRNA6 and CHRNA7 was found in the cluster headache group compared to controls. Additionally, there were an increased RNA expression of MT1H and increased protein levels of MT3 along with a decreased RNA expression of DNMT1. A positive correlation was found between the RNA expression of CHRNA7 and MT1H and a negative correlation was found between CHRNA6 and DNMT1 . Conclusion: Indirect evidence indicates heavy metal exposure in relation to cluster headache as well as a tendency for alterations in global DNA methylation. This supports the hypothesis that heavy metal exposure from smoking contributes towards the pathophysiology of cluster headache.