The Prevalence and Incidence of Cluster Headache: A Norwegian Population-Based Time-Trend Study.

The prevalence of cluster headache is 0.1% and cluster headache is often not diagnosed or misdiagnosed as migraine or sinusitis. In cluster headache there is often a considerable diagnostic delay - an average of 7 years in a population-based survey. Cluster headache is characterized by very severe or severe orbital or periorbital pain with a duration of 15-180 minutes. The cluster headache attacks are accompanied by characteristic associated unilateral symptoms such as tearing, nasal congestion and/or rhinorrhoea, eyelid oedema, miosis and/or ptosis. In addition, there is a sense of restlessness and agitation. Patients may have up to eight attacks per day. Episodic cluster headache (ECH) occurs in clusters of weeks to months duration, whereas chronic cluster headache (CCH) attacks occur for more than 1 year without remissions. Management of cluster headache is divided into acute attack treatment and prophylactic treatment. In ECH and CCH the attacks can be treated with oxygen (12 L/min) or subcutaneous sumatriptan 6 mg. For both oxygen and sumatriptan there are two randomized, placebo-controlled trials demonstrating efficacy. In both ECH and CCH, verapamil is the prophylactic drug of choice. Verapamil 360 mg/day was found to be superior to placebo in one clinical trial. In clinical practice, daily doses of 480-720 mg are mostly used. Thus, the dose of verapamil used in cluster headache treatment may be double the dose used in cardiology, and with the higher doses the PR interval should be checked with an ECG. At the start of a cluster, transitional preventive treatment such as corticosteroids or greater occipital nerve blockade can be given. In CCH and in long-standing clusters of ECH, lithium, methysergide, topiramate, valproic acid and ergotamine tartrate can be used as add-on prophylactic treatment. In drug-resistant CCH, neuromodulation with either occipital nerve stimulation or deep brain stimulation of the hypothalamus is an alternative treatment strategy. For most cluster headache patients there are fairly good treatment options both for acute attacks and for prophylaxis. The big problem is the diagnosis of cluster headache as demonstrated by the diagnostic delay of 7 years. However, the relatively short-lasting attack of pain in one eye with typical associated symptoms should lead the family doctor to suspect cluster headache resulting in a referral to a neurologist or a headache centre with experience in the treatment of cluster headache.

Cluster headache is a trigemino-autonomic cephalgia with a low prevalence. Several population-based studies on its prevalence and incidence have been performed, but with different methodology resulting in different figures. We analysed all available population-based epidemiological studies on cluster headache and compared the data in a meta-analysis. The pooled data showed a lifetime prevalence of 124 per 100,000 [confidence interval (CI) 101, 151] and a 1-year prevalence of 53 per 100,000 (CI 26, 95). The overall sex ratio was 4.3 (male to female), it was higher in chronic cluster headache (15.0) compared with episodic cluster headache (3.8). The ratio of episodic vs. chronic cluster headache was 6.0. Our analysis revealed a relatively stable lifetime prevalence, which suggests that about one in 1000 people suffers from cluster headache, the prevalence being independent of the region of the population study. The sex ratio (male to female) is higher than published in several patient-based epidemiological studies.

BackgroundThere is lack of population-based studies evaluating the prevalence of paroxysmal hemicrania, hemicrania continua and short-lasting unilateral neuralgiform headache attacks.ObjectivesThe aim of this study was to investigate the gender-specific 1-year prevalence of cluster headache, paroxysmal hemicrania, hemicrania continua, and short-lasting unilateral neuralgiform headache attacks.MethodsA nationwide study was conducted from January 1 2022 and December 31 2022 by linking diagnostic codes from Norwegian Patient Registry and prescription of relevant drugs from Norwegian Prescription Database on an individual basis. The 1-year prevalence with 95% confidence intervals (CI) of cluster headache, paroxysmal hemicrania, hemicrania continua and short-lasting unilateral neuralgiform headache attacks are estimated based on the combination of diagnostic codes, prescription of drugs and corresponding reimbursement codes.ResultsAmong 4,316,747 individuals aged ≥ 18 years, the 1-year prevalence per 100,000 was 14.6 (95% CI 13.5–15.8) for cluster headache, 2.2 (95% CI 1.8–2.7) for hemicrania continua, 1.4 (95% CI 1.0–1.8) for paroxysmal hemicrania, and 1.2 (95% CI 0.8–1.4) for short-lasting unilateral neuralgiform headache attacks. For all the trigeminal autonomic cephalalgies, cluster headache included, the prevalence was higher for women than men.ConclusionsIn this nationwide register-based study, we found a 1-year prevalence per 100,100 of 14.6 for cluster headache, 2.2 for hemicranias continua, 1.4 for paroxysmal hemicranias, and 1.2 for short-lasting unilateral neuralgiform headache attacks. This is the first study reporting higher prevalence of cluster headache for women than men.

Prevalence of cluster headache (CH) is estimated at 56 to 69 per 100,000. To calculate the CH lifetime prevalence in a sample representative of the Italian general population over age 14 years. Possible CH cases according to the diagnostic criteria of the 1988 International Headache Society classification were screened from a sample of 10,071 patients (5,311 women and 4,760 men; mean age 50.4 years, SD 19.7 years) registered in the lists of seven Parma-based general practitioners (GPs), using a previously validated, specially designed, self-administered questionnaire. Seven thousand five hundred twenty-two subjects (74.7%; 3,971 women and 3,551 men; mean age 50.8 years, SD 19.0 years) responded to the questionnaire in their GP's office (n = 3,338; 1,885 women and 1,453 men) or at home by mail (n = 1,914; 1,030 women and 884 men) or by phone (n = 2,270; 1,056 women and 1,214 men). Of the 111 suspected cases (76 women and 35 men), 105 were seen by a neurologist and 6 were contacted on the phone. The diagnosis of CH was confirmed in 21 (9 women and 12 men), including 7 already followed at the authors' center for CH. Seventeen patients had episodic CH, and four (all men) had chronic CH. The estimated prevalence rate was 279 per 100,000 (95% CI 173 to 427), 227 per 100,000 (95% CI 104 to 431) in women, and 338 per 100,000 (95% CI 175 to 592) in men. These results point to a higher cluster headache lifetime prevalence than previous reports.

Purpose of ReviewPrevious studies have indicated a possible link between the prevalence of cluster headache (CH) and sunlight exposure. However, this theory has yet to be tested systemically. In this article, we aim to examine how latitude affects the prevalence and phenotypes of CH.Recent FindingsTo our knowledge, there is by far no article describing the effect of latitude on disease phenotype; thus, we performed a literature review. We noted positive effects of latitude on 1-year prevalence, the proportion of chronic CH, and the proportion of miosis and/or ptosis.SummaryLatitude may affect the phenotypic presentations of cluster headache, probably partially mediated via temperature and sunlight variations. Still, other factors, such as environmental exposure to smoking and the genetic difference between the Eastern and Western populations, may participate in the pathogenesis and clinical manifestations of CH.

Despite being an excruciating headache, little is known about the burden of cluster headache (CH) regarding its various subtypes. In a multicentre, prospective study, patients with chronic CH (n = 27), with episodic CH in the active (n = 26) and outside the active period (n = 22), migraine patients (n = 24) and healthy controls (n = 31) were included. Epidemiological data, the German version of the Headache Disability Inventory (HDI) and a screening for psychiatric complaints were applied. About 25% of chronic CH patients in our study received invalidity allowance due to CH. HDI scores (total and subscales emotion and function) indicated a severe headache-specific disability (one-way ANOVA: P < 0.01). Patients with chronic and active episodic CH were significantly more affected than patients with inactive CH and migraine. Healthy volunteers were significantly less affected than all headache patients. Symptoms suggestive of psychiatric co-morbidity were found predominantly in chronic CH: depressive symptoms (56%), signs of agoraphobia (33%) and suicidal tendencies (25%) were frequently reported. Patients with chronic and active episodic CH were severely impaired in non-economic and economic domains such as disability, working life and psychiatric complaints. Remarkably, psychiatric co-morbidity was highest in chronic CH. Thus, especially chronic CH warrants special medical and further supportive care.

Alcohol and Cluster Headaches

Cluster headache is a primary headache disorder diagnosed according to the criteria of the International Headache Society.1 Previous epidemiological studies have shown prevalence rates of 0.056–0.38%. These were lifetime prevalence...

Cluster headache stands among the worst debilitating pain conditions. Available treatments for cluster headache have often disabling side effects, are not tolerated, or are ineffective. The management of drug-refractory chronic forms is challenging. New treatments are warranted and reported here. In cluster headache acute treatment, delivery systems like Demand Valve Oxygen or nonrebreather-type masks could enhance the effectiveness of inhaled oxygen therapy. Noninvasive vagus nerve stimulation relieves cluster headache pain at short-term in episodic patients. Sphenopalatine ganglion stimulation combines acute and preventive properties in subsets of patients and is of interest in selected refractory chronic forms. In cluster headache prevention, 'hypothalamic' deep brain stimulation is being refined using slightly different stereotactic coordinates or lower risk methods like endoventricular stimulation. Anti-CGRP monoclonal antibodies provide interesting results in episodic cluster headache, have a good safety profile, but do not appear effective in chronic cluster headache. These novel approaches provide additional alternatives to conventional cluster headache management, but results obtained in chronic forms are often disappointing. Research on cluster headache is often hampered by the lack of awareness in the medical world and by the relatively low prevalence of cluster headache compared with migraine. However, common features shared by these two primary headaches could help developing disease-specific therapies.

To estimate the prevalence of cluster headache in working-aged people, compare sickness absence rates and disability pension in cluster headache patients to rates in a matched comparison group, and explore associations of sociodemographic factors with such rates. Through population-based registers, we identified 3,240 people aged 16-64, living in Sweden in 2010, who at least once during 2001-2010 received inpatient or specialized outpatient health care with cluster headache (ICD-10 code G44.0) as main diagnosis. A comparison group (n = 16,200), matched for age, sex, type of living area, and educational level, from the total population aged 16-64 (n = 5,945,895) was used. Outcomes were sickness absence (>14 days) and disability pension during 2010. Crude and adjusted prevalence rates and odds ratios with 95% confidence intervals were computed. The prevalence of cluster headache in working-aged people was 0.054%. In 2010, 17.30% of the cluster headache group and 9.16% of the comparison group had been on sickness absence. In the cluster headache group, female patients had higher sickness absence rates (25.31%) and full-time disability pension (13.17%) than male patients (13.38% and 8.79%). Cluster headache patients older than 35 had higher rates than those of the same age in the comparison group. Further, cluster headache patients born outside Sweden were more likely to have full-time disability pension than patients born in Sweden. Much higher rates of the patients had sickness absence or disability pension than in the comparison group. Further shown differences related to sex, age, and other sociodemographic factors need to be addressed.

Cluster headache is associated with compensated hypogonadism in males, suggesting impaired testicular steroidogenesis. It is unknown if adrenal steroidogenesis is dysregulated and how this is linked to cluster headache pathophysiology. We therefore aimed to define the adrenal steroid profile in cluster headache and define the differences between the phases of episodic cluster headache. We secondarily aimed to assess whether the steroid profile could distinguish between chronic cluster headache and episodic cluster headache. A prospective case-control study containing adult males with chronic cluster headache (n = 60), paired episodic cluster headache in and out of bout (n = 60) and healthy controls (n = 60). A fasted serum steroid profile for 16 steroid hormones was assessed via liquid chromatography tandem mass-spectrometry, assessing mineralocorticoids, glucocorticoids, and androgens. Explorative machine learning was used to segregate the cluster headache states. The mineralocorticoids 11-deoxycorticosterone (P < 0.05), corticosterone (P < 0.05) and aldosterone (P < 0.05) were lower in those with episodic cluster headache compared to controls. 11-deoxycorticosterone (P < 0.01), corticosterone (P < 0.01), and the glucocorticoids 11-deoxycortisol (P < 0.01) and cortisol (P < 0.05) and cortisol/DHEAS ratio (P < 0.001) are lower in episodic in bout compared to their paired remission state. Those with chronic cluster headache had lower concentrations of 17-OH pregnenolone (P < 0.05) and DHEAS (P < 0.001) and a higher cortisol/DHEAS ratio (P < 0.01). The steroid hormone profile distinguished between chronic and episodic cluster in bout with a specificity of 86% (95%CI: 69%-90%), sensitivity of 81% (95%CI: 73%-93%) and AUC of 0.92 (P < 0.0001). Attack frequency and time from last attack correlated with the degree of steroid dysfunction in episodic cluster headache but not in chronic cluster headache. We identify distinct steroid hormone profiles in episodic and chronic cluster headache. Episodic in bout was associated with reduced adrenal steroid synthesis that resolves in remission. Chronic cluster headache was associated with stress induced androgen suppression. Together, these differences are likely secondary to cluster headache and may reflect distinct neurobiological bases underlying episodic and chronic cluster headache. Not applicable.

Introduction Chronic cluster headache is rare and some of these patients become drug-resistant. Occipital nerve stimulation has been successfully employed in open studies to treat chronic drug-resistant cluster headache. Data from large group of occipital nerve stimulation-treated chronic cluster headache patients with long duration follow-up are advantageous. Patients and methods Efficacy of occipital nerve stimulation has been evaluated in an experimental monocentric open-label study including 35 chronic drug-resistant cluster headache patients (mean age 42 years; 30 men; mean illness duration: 6.7 years). The primary end-point was a reduction in number of daily attacks. Results After a median follow-up of 6.1 years (range 1.6-10.7), 20 (66.7%) patients were responders (≥50% reduction in headache number per day): 12 (40%) responders showed a stable condition characterized by sporadic attacks, five responders had a 60-80% reduction in headache number per day and in the remaining three responders chronic cluster headache was transformed in episodic cluster headache. Ten (33.3%) patients were non-responders; half of these have been responders for a long period (mean 14.6 months; range 2-48 months). Battery depletion (21 patients 70%) and electrode migration (six patients - 20%) were the most frequent adverse events. Conclusions Occipital nerve stimulation efficacy is confirmed in chronic drug-resistant cluster headaches even after an exceptional long-term follow-up. Tolerance can occur years after improvement.

Based on a preceding survey performed in 1985, the authors estimated the prevalence and incidence of cluster headache (CH) in the Republic of San Marino (26,628 inhabitants at 31 December 1999). All cases were diagnosed by direct interview according to International Headache Society criteria. The prevalence rate was 56/100,000 (95% CI 31.3 to 92.4), and the incidence rate was 2.5/100,000/year (95% CI 1.14 to 4.75). Most cases showed rare clusters. This is the first prospective study on the incidence of CH.

Neurology. 2002 May 14;58(9):1407‐1409Based on a preceding survey performed in 1985, the authors estimated the prevalence and incidence of cluster headache (CH) in the Republic of San Marino (26 628 inhabitants at 31 December 1999). All cases were diagnosed by direct interview according to International Headache Society criteria. The prevalence rate was 56/100 000 (95% CI 31.3 to 92.4), and the incidence rate was 2.5/100 000/year (95% CI 1.14 to 4.75). Most cases showed rare clusters. This is the first prospective study on the incidence of CH.Comment: There continues to be debate on the prevalence of cluster in the general population. Since San Marino is small, the entire cluster population, with a smaller denominator for the general population, could be estimated, making this a very important study. SJT

AimTo prospectively determine subtype shift, relapse rate and risk factors of frequent relapse in cluster headache (CH).MethodsThis multicenter cohort study recruited patients with CH at baseline visits between September 2016 and January 2019 and planned to prospectively follow them up for up to five years. The subtype (episodic vs. chronic) was reassessed at baseline visit 2 (2-4 weeks) and serial follow-up visits if unremitted. We assessed the subtype shift of the index bout (i.e. the bout at the baseline visit) in all patients and relapse rates in those with episodic CH who were in an active bout at the time of recruitment. Relapse (i.e. bout recurrence) was prospectively collected via clinic visit or telephone interview at 3 ± 1 months, 1, 2, 3, 4 and 5 years (each ±6 months) after the baseline visit. Risk factors of frequent relapse were analyzed by comparing the incidence rate ratio (IRR) of relapse using Poisson regression analysis (model 1, static variables in all patients; model 2, time-related variables in patients with two or more lifetime bouts) accounted for different follow-up periods using an offset term.ResultsIn 295 patients (58 with first-ever bouts) enrolled, CH subtypes were episodic, chronic and unclassified in 252, 11 and 32 at baseline. At baseline V2, CH subtype was re-determined to be chronic in seven (12.1%) of 58 patients with first-onset CH ("primary chronic CH") and nine (3.8%) of 237 with a history of episodic CH ("secondary chronic CH"). When excluding known chronic CHs at baseline, the incidence of chronic CH newly found during a prospective observation was 3.8% in patients with first-onset CH and 1.4% in those with a history of episodic CH. In 244 patients with episodic CH in an active bout at the time of recruitment, the relapse rate was 0.29 (95% confidence interval (CI) = 0.27-0.32; p < 0.001) per person-year after 5.9 ± 1.37 follow-up visits over a mean duration of 4.2 ± 1.32 years. Models 1 and 2 indicated that age (adjusted IRR = 0.97; 95% CI = 0.95-0.98), longer disease duration (adjusted IRR = 0.97; 95% CI = 0.95-1.00), first-ever bout (adjusted IRR = 0.35; 95% CI = 0.20-0.57), regular (one or more per week) alcohol consumption (adjusted IRR = 0.60; 95% CI = 0.45-0.81), and longer between-bout interval of previous bouts (adjusted IRR = 0.72; 95% CI = 0.60-0.87) were associated with less relapse. Seasonal rhythmicity (adjusted IRR = 1.66; 95% CI = 1.20-2.33) and increasing attack intensity across bouts (adjusted IRR = 1.66; 95% CI = 1.06-2.59) were associated with frequent relapse.ConclusionsThe present study provides data on the subtype shift and relapse rate of CH based on the prospective observation. Although our observation is only limited to a five-year time frame, our findings may suggest that disease activity increases after onset and then regress with age and time, and that seasonal rhythmicity and increasing attack intensity across bouts indicate higher propensity to relapse.