Cluster Headache, SUNCT, and SUNA.

OBJECTIVE: This article reviews the epidemiology, clinical features, differential diagnosis, pathophysiology, and management of three types of trigeminal autonomic cephalalgias: cluster headache (the most common), short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA). LATEST DEVELOPMENTS: The first-line treatments for trigeminal autonomic cephalalgias have not changed in recent years: cluster headache is managed with oxygen, triptans, and verapamil, and SUNCT and SUNA are managed with lamotrigine. However, new successful clinical trials of high-dose prednisone, high-dose galcanezumab, and occipital nerve stimulation provide additional options for patients with cluster headache. Furthermore, new genetic and imaging tests in patients with cluster headache hold promise for a better understanding of its pathophysiology. ESSENTIAL POINTS: The trigeminal autonomic cephalalgias are a group of diseases that appear similar to each other and other headache disorders but have important differences. Proper diagnosis is crucial for proper treatment.

Profile of Chinese Cluster Headache Register Individual Study (CHRIS): Clinical characteristics, diagnosis and treatment status data of 816 patients in China.

BACKGROUND: The clinical profile of cluster headache may differ among different regions of the world, warranting interest in the data obtained from the initial Chinese Cluster Headache Register Individual Study (CHRIS) for better understanding. METHODS: We conducted a multicenter, prospective, longitudinal cohort study on cluster headache across all 31 provinces of China, aiming to gather clinical characteristics, treatment approaches, imaging, electrophysiological and biological samples. RESULTS: In total 816 patients were enrolled with a male-to-female ratio of 4.33:1. The mean age at consultation was 34.98 ± 9.91 years, and 24.89 ± 9.77 years at onset. Only 2.33% were diagnosed with chronic cluster headache, and 6.99% had a family history of the condition. The most common bout was one to two times per year (45.96%), lasting two weeks to one month (44.00%), and occurring frequently in spring (76.23%) and winter (73.04%). Of these, 68.50% experienced one to two attacks per day, with the majority lasting one to two hours (45.59%). The most common time for attacks was between 9 am and 12 pm (75.86%), followed by 1 am and 3 am (43.48%). Lacrimation (78.80%) was the most predominant autonomic symptom reported. Furthermore, 39.22% of patients experienced a delay of 10 years or more in receiving a correct diagnosis. Only 35.67% and 24.26% of patients received common acute and preventive treatments, respectively. CONCLUSION: Due to differences in ethnicity, genetics and lifestyle conditions, CHRIS has provided valuable baseline data from China. By establishing a dynamic cohort with comprehensive multidimensional data, it aims to advance the management system for cluster headache in China.

One-year prevalence of cluster headache, hemicrania continua, paroxysmal hemicrania and SUNCT in Norway: a population-based nationwide registry study.

BACKGROUND: There is lack of population-based studies evaluating the prevalence of paroxysmal hemicrania, hemicrania continua and short-lasting unilateral neuralgiform headache attacks. OBJECTIVES: The 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. METHODS: A 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. RESULTS: Among 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. CONCLUSIONS: In 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.

Epidemiology, burden and clinical spectrum of cluster headache: a global update.

BACKGROUND: This narrative review aims to broaden our understanding of the epidemiology, burden and clinical spectrum of cluster headache based on updated findings with a global perspective. METHODS: We conducted a literature search on the following topics: (a) epidemiology; (b) burden: quality of life, disability, economic burden, job-related burden and suicidality; and (c) clinical spectrum: male predominance and its changes, age, pre-cluster and pre-attack symptoms, aura, post-drome, attack characteristics (location, severity, duration and associated symptoms), bout characteristics (attack frequency, bout duration and bout frequency), circadian and seasonal rhythmicity and disease course. RESULTS: New large-scale population-based reports have suggested a lower prevalence than previous estimations. The impact of cluster headache creates a significant burden in terms of the quality of life, disability, economic and job-related burdens and suicidality. Several studies have reported decreasing male-to-female ratios and a wide age range at disease onset. The non-headache phases of cluster headache, including pre-cluster, pre-attack and postictal symptoms, have recently been revisited. The latest data regarding attack characteristics, bout characteristics, and circadian and seasonal rhythmicity from different countries have shown variability among bouts, attacks, individuals and ethnicities. Studies on the disease course of cluster headache have shown typical characteristics of attacks or bouts that decrease with time. CONCLUSIONS: Cluster headache may be more than a "trigeminal autonomic headache" because it involves complex central nervous system phenomena. The spectrum of attacks and bouts is wider than previously recognised. Cluster headache is a dynamic disorder that evolves or regresses over time.

Clinical characteristics and treatment patterns of patients with episodic cluster headache: results from the United States, United Kingdom and Germany.

OBJECTIVE: To describe clinical characteristics and regional treatment patterns of episodic cluster headache (CH). METHODS: A point-in-time survey of physicians and their patients with CH was conducted in the United States, United Kingdom and Germany in 2017. RESULTS: Overall, 1012 patients with episodic CH were analyzed. Demographic and clinical findings were generally consistent across regions. Most patients were men (66.6%) and the mean age was 40.9 years. The greatest proportion of patients (38.3%) had ≤1 attack per day. The mean number of attacks per day (APD) was 2.4 and mean number of cluster periods per year was 2.6; the mean cluster period duration was 30.8 days. Most patients (69.3%) did not report a specific or predicable time when cluster periods occurred. Acute treatment was prescribed for 47.6% of patients, 10.3% of patients received preventive treatment, and 37.9% of patients received combined acute and preventive treatment; 4.2% of patients were not receiving treatment. Frequently prescribed acute treatments were sumatriptan, oxygen, and zolmitriptan; oxygen use varied considerably across countries and was prescribed least often in the United States. Frequently prescribed preventive treatments were verapamil, topiramate, and lithium. Lack of efficacy and tolerability were the most common reasons for discontinuing preventive treatment. CONCLUSIONS: We observed high use of acute treatments, but only half of patients used preventive treatments despite experiencing several cluster periods per year with multiple cluster APD. Further studies about the need for and benefits of preventive treatment for episodic CH are warranted.

People with cluster headache (CH) experience headache attacks of excruciating stabbing pain, usually on one side of the head around the eye. These headache attacks typically last between 15 min and 3 h, and come in clusters (or bouts) occurring up to several times a day for a few weeks or months at a time. This greatly impacts a patient's quality of life.We surveyed doctors and their patients across the United States, the United Kingdom and Germany, looking at symptoms that occurred during CH attacks, how long the headache attacks lasted, how often the patient had them, and what medicines were being given.Our results showed that patients with CH suffered from clusters (bouts) of headache attacks several times a year. Nearly, a third of patients had a wrong diagnosis before being diagnosed with CH. Patients experienced stress, agitation, restlessness, difficulty relaxing and depression during a headache attack, especially those who had more CH attacks each day.Although many patients were taking medication, only half of patients were prescribed medicines to prevent their headache attack from starting. Side effects and the medicines not working were the most common reasons patients stopped taking medicine to prevent their headache attacks. The differences seen in medicines prescribed between countries suggest differences in guidance, or in doctors' awareness of current medication guidelines. Further studies about the need for and benefits of medicines to prevent CH attacks are needed.

Cluster Headache Genomewide Association Study and Meta-Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor.

OBJECTIVE: The objective of this study was to aggregate data for the first genomewide association study meta-analysis of cluster headache, to identify genetic risk variants, and gain biological insights. METHODS: A total of 4,777 cases (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from 10 European and 1 East Asian cohorts. We first performed an inverse-variance genomewide association meta-analysis of 4,043 cases and 21,729 controls of European ancestry. In a secondary trans-ancestry meta-analysis, we included 734 cases and 9,846 controls of East Asian ancestry. Candidate causal genes were prioritized by 5 complementary methods: expression quantitative trait loci, transcriptome-wide association, fine-mapping of causal gene sets, genetically driven DNA methylation, and effects on protein structure. Gene set and tissue enrichment analyses, genetic correlation, genetic risk score analysis, and Mendelian randomization were part of the downstream analyses. RESULTS: The estimated single nucleotide polymorphism (SNP)-based heritability of cluster headache was 14.5%. We identified 9 independent signals in 7 genomewide significant loci in the primary meta-analysis, and one additional locus in the trans-ethnic meta-analysis. Five of the loci were previously known. The 20 genes prioritized as potentially causal for cluster headache showed enrichment to artery and brain tissue. Cluster headache was genetically correlated with cigarette smoking, risk-taking behavior, attention deficit hyperactivity disorder (ADHD), depression, and musculoskeletal pain. Mendelian randomization analysis indicated a causal effect of cigarette smoking intensity on cluster headache. Three of the identified loci were shared with migraine. INTERPRETATION: This first genomewide association study meta-analysis gives clues to the biological basis of cluster headache and indicates that smoking is a causal risk factor. ANN NEUROL 2023;94:713-726.

Clinical Profile of Chronic Cluster Headaches in a Regional Headache Center in Japan.

Objective Little is known about the prevalence and characteristics of chronic cluster headache (CCH) in Japan. We therefore characterized the clinical profile of CCH in Japan by surveying patients with CCH who were registered at a Japanese regional headache center. We also reviewed the existing literature for the prevalence and clinical characteristics of CCH reported in various populations. Methods In this single-center retrospective study, we assessed consecutive patients with cluster headache (CH) who visited a regional tertiary headache center between February 2011 and July 2020. They were treated following the Clinical Practice Guideline for Chronic Headache 2013. We compared their demographic characteristics and clinical features according to the CCH onset pattern (primary vs. secondary). Results Of 420 patients with CH, 19 (4.2%) had CCH (9 primary and 10 secondary). The incidence of CCH in Japan is relatively low compared to that in Western countries but is comparable to that in other Asian countries. CCH showed a higher predominance of men than women. Compared to primary CCH, secondary CCH included a higher proportion of current smokers and older patients during clinic visits. Subcutaneous sumatriptan and oxygen inhalation were the most common abortive treatments, and oral prednisolone and verapamil were the most common preventive treatments. Home oxygen therapy was effective in six of seven patients. Only two patients with coexisting migraine received calcitonin gene-related peptide (CGRP)-targeted therapies. Conclusions CCH remains refractory to treatment. Improving treatment outcomes will require maximizing the use of currently available drugs and expanding the use of neuromodulation, nerve block, and CGRP-targeted therapies.

Comorbidity or combination - more evidence for cluster-migraine?

BACKGROUND: While migraine and cluster headache share some clinical features and therapies, they differ considerably in the frequency and duration of the headache, as well as the inter-attack, or inter-bout, pathophysiology. Neither is fully understood, with their shared pathways being of interest. FINDINGS: Five patients for whom it was difficult to distinguish migraine from cluster headache are presented. They had aspects of their phenotypes, which could be attributed to both disorders. Each patient was thoroughly examined, excluding secondary causes of headache, and had been treated with a number of medicines. CONCLUSION: A correct diagnosis is key to the appropriate treatment approach. Especially, if treatment is not successful for the suspected headache type, and enlargement of the diagnostic and therapeutic range, respectively, should be evaluated. Whether in such settings there is shared or different pathophysiology can only be speculated upon.

Multimorbidity and Sickness Absence/Disability Pension in Patients With Cluster Headache and Matched References: A Swedish Register-Based Study.

BACKGROUND AND OBJECTIVES: Multimorbidity among patients with cluster headache (CH) is considered to be high, but large studies are lacking. The aims were to explore the occurrence of diagnosis-specific multimorbidity among patients with CH and matched references and possible associations of this with their sickness absence and disability pension. METHODS: We performed a register-based study of patients with CH and matched references, regarding their multimorbidity, sickness absence, and disability pension. Data were obtained from 2 nationwide registers: Statistics Sweden's Longitudinal Integration Database for Health Insurance and Labor Market Studies (LISA) (for sociodemographics in 2009, sickness absence, and disability pension in 2010) and The National Board of Health and Welfare's specialized outpatient and inpatient registers for diagnosis-specific health care in 2001-2010 (for identifying patients with CH and multimorbidity, defined by ICD-10 codes). The prevalence and number of net days of sickness absence and/or disability pension in 2010 were calculated, in general and by multimorbidity. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated for comparison of each diagnostic group with references without the chosen morbidity. RESULTS: We analyzed 3,240 patients with CH, aged 16-64 years, and living in Sweden in 2010 and 16,200 matched references. A higher proportion of patients with CH had multimorbidity (91.9%) than of references (77.6%), OR 3.263 (95% CI 2.861-3.721), both in general and regarding all analyzed diagnostic groups. Differences were particularly high for diagnoses relating to the nervous (CH 51.8% vs references 15.4%), OR 5.922 (95% CI 5.461-6.422), and musculoskeletal (CH 39.0% vs references 23.7%), OR 2.057 (95% CI 1.900-2.227), systems. Multimorbidity rates were overall higher among women in patients with CH (96.4% vs men 89.6%). Patients with CH had a higher mean number of days of sickness absence and disability pension compared with references, 63.15 vs 34.08 days. Moreover, multimorbidity was associated with a higher mean number of such days in patients with CH, 67.25, as compared with references, 40.69 days. DISCUSSION: The proportions of multimorbidity were high in both patients with CH and references, however, higher in the patients with CH, who also had higher sickness absence and disability pension levels. In particular, CH patients with multimorbidity and of female sex had high sickness absence and disability pension levels.

Sex Differences in Clinical Features, Treatment, and Lifestyle Factors in Patients With Cluster Headache.

BACKGROUND AND OBJECTIVES: Cluster headache is considered a male-dominated disorder, but we have previously suggested that female patients may display a more severe phenotype. Studies on sex differences in cluster headache have been conflicting; therefore, this study, with the largest validated cluster headache material at present, gives more insights into sex-specific characteristics of the disease. The objective of this study was to describe sex differences in patient demographics, clinical phenotype, chronobiology, triggers, treatment, and lifestyle in a Swedish cluster headache population. METHODS: Study participants were identified by screening medical records from 2014 to 2020, requested from hospitals and neurology clinics in Sweden for the ICD-10 code G44.0 for cluster headache. Each study participant answered a detailed questionnaire on clinical information and lifestyle, and all variables were compared with regard to sex. RESULTS: A total of 874 study participants with a verified cluster headache diagnosis were included. Of the participants, 575 (66%) were male and 299 (34%) were female, and biological sex matched self-reported sex for all. Female participants were to a greater extent diagnosed with the chronic cluster headache subtype compared with male participants (18% vs 9%, p = 0.0002). In line with this observation, female participants report longer bouts than male participants (p = 0.003) and used prophylactic treatment more often (60% vs 48%, p = 0.0005). Regarding associated symptoms, female participants experienced ptosis (61% vs 47%, p = 0.0002) and restlessness (54% vs 46%, p = 0.02) more frequently compared with male participants. More female than male study participants had a positive family history of cluster headache (15% vs 7%, p = 0.0002). In addition, female participants reported diurnal rhythmicity of their attacks more often than male participants (74% vs 63%, p = 0.002). Alcohol as a trigger occurred more frequently in male participants (54% vs 48%, p = 0.01), whereas lack of sleep triggering an attack was more common in female participants (31% vs 20%, p = 0.001). DISCUSSION: With this in-depth analysis of a well-characterized cluster headache population, we could demonstrate that there are significant differences between male and female participants with cluster headache, which should be regarded at the time of diagnosis and when choosing treatment options. The data suggest that female patients generally may be more gravely affected by cluster headache than male patients.

Sex-related differences in cluster headache: A hospital-based study in Taiwan.

OBJECTIVES: To compare the clinical profiles between male and female cluster headache patients from a large cohort. METHODS: This hospital-based study enrolled patients diagnosed with cluster headache between 1997 to 2021. Participants completed structured questionnaires collecting information on demographics, clinical profiles, and quality of life. Treatment regimens and effectiveness were determined through medical chart review. All variables were compared between the sexes. RESULTS: In total, 798 patients (M/F:659/139) were enrolled. The male-to-female ratio was 4.7:1 for the full study period, but it declined from 5.2:1 to 4.3:1 for patients enrolled before and after 2010, respectively. The frequencies of chronic cluster headache (M:1.2%, F:1.4%) and aura (M:0.3%, F:0.7%) were low but similar between the sexes. Most headache features showed no difference between men and women. Female patients had significantly longer attack duration, shorter inter-bout duration, higher frequencies for eyelid edema, nausea and vomiting and lower frequencies for conjunctival injection and pacing. Sex difference did not influence headache-associated disability, anxiety, or depression, but poor sleep quality was significantly more common in women. Among menstruating women, 22/122 (18.0%) reported worsening headaches during menses. The effectiveness of treatment was similar between the sexes. CONCLUSIONS: Despite a decline of male-to-female ratio in the past two decades, most clinical profiles were similar between the sexes.

Pre-attack and pre-episode symptoms in cluster headache: a multicenter cross-sectional study of 327 Chinese patients.

BACKGROUND: There have been a few studies regarding the pre-attack symptoms (PAS) and pre-episode symptoms (PES) of cluster headache (CH), but none have been conducted in the Chinese population. The purpose of this study was to identify the prevalence and features of PAS and PES in Chinese patients, as well as to investigate their relationships with pertinent factors. METHODS: The study included patients who visited a tertiary headache center and nine other headache clinics between January 2019 and September 2021. A questionnaire was used to collect general data and information about PAS and PES. RESULTS: Among the 327 patients who met the CH criteria (International Classification of Headache Disorders, 3rd edition), 269 (82.3%) patients experienced at least one PAS. The most common PAS were head and facial discomfort (74.4%). Multivariable logistic regression analysis depicted that the number of triggers (OR = 1.798, p = 0.001), and smoking history (OR = 2.067, p = 0.026) were correlated with increased odds of PAS. In total, 68 (20.8%) patients had PES. The most common symptoms were head and facial discomfort (23, 33.8%). Multivariable logistic regression analysis showed that the number of triggers were associated with increased odds of PES (OR = 1.372, p = 0.005). CONCLUSIONS: PAS are quite common in CH patients, demonstrating that CH attacks are not comprised of a pain phase alone; investigations of PAS and PES could help researchers better understand the pathophysiology of CH.

Seasonal changes of internet searching suggest circannual rhythmicity of primary headache disorders.

OBJECTIVE: To investigate whether web searching for headache disorders presents some circannual rhythm. BACKGROUND: Studies support the influence of seasonal rhythms in primary headache disorders such as cluster headache (CH) and episodic migraine. We investigated whether internet users' searching for headaches reflect these circannual rhythms. METHODS: This was an internet-based study using the Google Trends (Google) platform. The 10-year interest across four related topics (headache, migraine, tension-type headache [TTH], and CH) in 31 European countries was scanned. RESULTS: Significant differences between months were found for the topics "headache" and "migraine." Interest in the former was superior in February (median for all countries, 61 [25th-75th percentile, 45-80]), October (61 [44-75]), and November (61 [45-76]). The lowest search volumes for headache appeared in July (52 [37-66]) (p < 0.001). Migraine was searched most commonly in November (56 [40-73]) and rarely in June (46.5 [31-64]) (p < 0.001). Differences were observed for the topic of headache in Northern Europe (p = 0.001) and for headache and migraine in Central Europe (p < 0.001 and p = 0.016 respectively) but not in the southern region. TTH and CH were apparently less searched and no evident trends regarding them were present (median, 22 [0-44] for TTH and 15 [0-33] for CH; direct popularity comparison: headache 56 [44-63], migraine 16 [12-24], TTH 2 [1-2], and CH 2 [1-2]; between-month differences, p = 0.168 and p = 0.081 respectively). CONCLUSIONS: Public attention on headache-related topics on the internet is distributed according to a significant trend of increased searching around spring and autumn. It suggests that a large number of patients may experience some level of seasonal variation in their headaches. Assessment of whether those temporal changes are present in clinical practice is necessary.

The clinical characteristics of familial cluster headache.

BACKGROUND: A positive family history predisposes to the development of cluster headache. The distinct characteristics of familial cluster headache have yet to be confirmed, however, evidence suggests a younger age of onset and higher proportion of females in this subgroup. OBJECTIVES: To assess the rate and mode of inheritance of familial cluster headache in a tertiary referral centre for headache. To describe the clinical features of familial cluster headache. METHODS: A retrospective study conducted between 2007 and 2017. Cluster headache was confirmed in probands and affected relatives. Differences in demographics, clinical characteristics, and response-to-treatment in familial cluster headache were delineated through multivariate analysis using a control cohort of 597 patients with sporadic cluster headache. RESULTS: Familial cluster headache was confirmed in 48 (7.44%) patients and predominantly reflected an autosomal dominant mode of inheritance with reduced penetrance. Familial cases were more likely to report nasal blockage (OR 4.06, 95% CI; 2.600-6.494, p < 0.001) during an attack and a higher rate of concurrent short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (OR 3.76, 95% CI; 1.572-9.953, p = 0.004). CONCLUSION: These findings add to evidence suggesting a genetic component to cluster headache. Here, we demonstrated prominent nasal blockage, and a higher occurrence of concomitant short-lasting unilateral neuralgiform headache with conjunctival injection and tearing in this subgroup, further delineating the phenotype.

Characteristics of pre-cluster symptoms in cluster headache: A cross-sectional multicentre study.

BACKGROUND: Contrary to pre-attack symptoms before an individual cluster headache attack, little is known about the pre-cluster symptoms before the onset of cluster bouts. We previously described pre-attack symptoms before cluster headache attacks. The aim of this study was to investigate characteristics of pre-cluster symptoms in patients with episodic cluster headache. METHODS: In this multicentre study, 184 patients with episodic cluster headache were recruited between October 2018 and December 2020. They were interviewed by investigators and completed a structured questionnaire. To investigate pre-cluster and pre-attack symptoms, we assessed 20 symptoms and signs using the questionnaire. RESULTS: The upcoming cluster bout was predictable in 35.3% (n = 65/184) of the patients. When present, pre-cluster symptoms occurred at a median duration of 7 days (interquartile range, 2.3-14 days) before the onset of the cluster bout. Patients with pre-cluster symptoms showed a higher proportion of women, prevalence of pre-attack symptoms and seasonal rhythmicity, frequency of cluster headache attacks per day, and total number of cluster bouts compared to patients without pre-cluster symptoms. In univariable and multivariable logistic regression analyses, female sex was associated with the predictability of pre-cluster symptoms (odds ratio = 2.297, p = 0.016). CONCLUSIONS: The upcoming cluster bout was predicted in approximately 35% of patients with episodic cluster headache, which may allow for an earlier preventive treatment and help understand the pathophysiology.

Cluster Headache: Rapid Evidence Review.

Cluster headache, the most common form of trigeminal autonomic cephalgia, is a rare primary headache disorder that affects less than 1% of the population. The mean age of onset is 30 years, and it is two to three times more common in males. Cluster headache consists of attacks of severe unilateral pain located in the orbital, supraorbital, and/or temporal region that occur from every other day up to eight times per day and last from 15 to 180 minutes. The pain is associated with ipsilateral autonomic symptoms (most commonly lacrimation, conjunctival injection, nasal congestion or rhinorrhea, ptosis, edema of the eyelid, sweating of the forehead or face, and miosis) and a sense of agitation or restlessness. Attacks occur in clusters, called bouts, and are episodic or chronic. Common triggers include alcohol, nitroglycerin, food containing nitrates, and strong odors. Abortive treatments include triptans and oxygen; transitional treatments include steroids and suboccipital steroid injections; and prophylactic treatments include verapamil, lithium, melatonin, and topiramate. Newer treatments for cluster headache include galcanezumab, neurostimulation, and somatostatin receptor agonists.

Cluster headache: a single tertiary center study.

OBJECT: The characteristics of cluster headache (CH) patients in many countries and the diagnostic and therapeutic approach have been described in several publications, but so far no clinical data have been published from Turkey. MATERIAL METHODS: This is a cross-sectional retrospective study that includes all patients who were diagnosed with CH and referred to our headache clinic, Dokuz Eylül University Faculty of Medicine, Neurology Department from 1991 to January 2018. RESULTS: We included 114 patients (24 females and 90 males) in our study. The mean age at onset was 31.68 ± 12.72 (range 13-68). Eighty-six (78.18%) patients had episodic cluster headache (ECH) and 24 (21.82%) patients had chronic cluster headache (CCH). The age at onset was significantly higher in the patients with CCH than with ECH (p = 0.002). The most common location was orbitotemporal for both genders. The most common accompanying symptoms were lacrimation (80.73%). The male:female ratio in all patients was 3:7, 3.8:1 in those with CCH and 4:1 in those with ECH. Eighty-nine (87.25%) patients had prophylactic treatment and 60 of them received verapamil. CONCLUSION: In our study, some clinical features of our patients were similar to those of Europe and America or the Asian countries and some of them not. There are regional differences in cluster headache patients. With more awareness of cluster headache and research from many countries, clinical differences can be revealed more objectively in the future.

Galcanezumab effectiveness on comorbid cluster headache and chronic migraine: a prospective case series.

BACKGROUND: Cluster headache (CH) and migraine are recurrent painful primary cephalalgies, typically with different clinical appearance and some shared features, such as unilateral pain, common triggers and response to triptans and/or monoclonal antibodies against the calcitonin gene-related peptide (CGRP) pathway. Common pathophysiological mechanisms are proposed in CH and migraine, including the role of the trigeminal-vascular system with its most representative neuropeptide, CGRP. Very few case series have been conducted so far investigating anti-CGRP treatments in patients with comorbid CH and migraine, and no cases have been reported which assess both CH and chronic migraine outcomes. CASE SERIES: We describe 4 patients with both chronic migraine and cluster headache, with or without failure to preventive medications. Galcanezumab (240 mg loading dose, followed by 120 mg monthly) was used for at least a 3-month treatment, demonstrating improvement in both migraine and CH outcomes (i.e. migraine days, CH attacks, Headache Impact Test -6 item score, acute medications use), achieving sustained clinical benefit. No adverse events were reported. DISCUSSION AND CONCLUSION: Taking into account the role of CGRP in migraine and CH pathophysiology, a usually well-tolerated treatment with CGRP blockade could be a rationale-based option to treat patients with coexisting chronic migraine and cluster headache. Additional studies are needed to assess the role of anti-CGRP drugs in episodic and chronic CH treatment, as well as to establish correct timing and patient prerequisites to begin therapy.

Cluster headache epidemiology including pediatric onset, sex, and ICHD criteria: Results from the International Cluster Headache Questionnaire.

OBJECTIVE: To validate the diagnoses and to investigate epidemiological data from an international, non-clinic-based, and large (n = 1604) survey of participants with cluster headache. BACKGROUND: There are several limitations in current epidemiological data in cluster headache including a lack of large non-clinic-based studies. There is also limited information on several aspects of cluster headache, such as pediatric incidence. METHODS: The International Cluster Headache Questionnaire was an internet-based survey that included questions on cluster headache demographics, criteria from the International Classification of Headache Disorders (ICHD), and medications. RESULTS: A total of 3251 subjects participated in the survey, and 1604 respondents met ICHD criteria for cluster headache. For validation, we interviewed a random sample of 5% (81/1604) of participants and confirmed the diagnosis of cluster headache in 97.5% (79/81). Pediatric onset was found in 27.5% (341/1583) of participants, and only 15.2% (52/341) of participants with pediatric onset were diagnosed before the age of 18. Men were more likely to have episodic cluster headache between ages 10 and 50, but the sex ratio was approximately equal for other ages. An overwhelming majority of respondents had at least one autonomic feature (99.0%, 1588/1604) and had restlessness (96.6%, 1550/1604), but many also had prototypical migrainous features including photophobia or phonophobia (50.1%, 804/1604), pain aggravated by physical activity (31.4%, 503/1604), or nausea and vomiting (27.5%, 441/1604). Interestingly, the first-line medications for acute treatment (oxygen) and preventive treatment (calcium channel blockers) were perceived as significantly less effective in chronic cluster headache (3.2 ± 1.1 and 2.1 ± 1.0 respectively on a 5-point ordinal scale) compared with episodic cluster headache (3.5 ± 1.0 and 2.4 ± 1.1, respectively, p < 0.001 for both comparisons). CONCLUSIONS: Cluster headache often occurs in the pediatric population, although they are typically not diagnosed until adulthood. The onset of cluster headache is the inverse of that in migraine; in migraine women are more likely to have migraine between ages 10 and 50 but the sex ratio is approximately equal otherwise. Prototypical migrainous features are not useful in differentiating cluster headache from migraine. Participant data from a large international study also suggest that chronic cluster headache is not only less responsive to newer treatments (like noninvasive vagus nerve stimulation and galcanezumab), but to traditional first-line treatments as well.