Pre-cluster symptoms in a Taiwanese cohort of cluster headache: symptom profiles and clinical predictions.

BACKGROUND: Pre-cluster symptoms (PCSs) are symptoms preceding cluster bouts and might have implications for the treatment of cluster headache (CH). This study investigated the prevalence of PCSs, and their utility in predicting upcoming bouts as well as the associations with therapeutic efficacy. METHODS: We prospectively collected data from patients with CH. Each patient received a structured interview and completed questionnaire surveys during CH bouts. In sub-study 1, we cross-sectionally analyzed the prevalence, symptomatology, and predictability of upcoming bouts. Overall, 34 PCSs, divided into seven categories, were queried, including head and neck pain, cranial autonomic symptoms, restlessness, fatigue or mood changes, sleep alterations, constitutional symptoms, and generalized pain. In sub-study 2, we recorded the weekly frequency of CH attacks after the initiation of verapamil concurrently with a 14-day transitional therapy based on the patients' headache diary. A responder to verapamil was defined as a patient who have a reduction from baseline of at least 50% in the weekly frequency of CH attacks 4 weeks after the initiation of verapamil. RESULTS: A total of 168 CH patients (women/men: 39/129) completed the study. In sub-study 1, we found 149 (88.7%) experienced PCSs, with a median of 24 (IQR 18 to 72) hours before the bouts. Up to 57.7% of patients with PCS reported that they could predict upcoming bouts. Among the seven categories of PCSs, head and neck pain was the most common (81.0%) and was associated with a higher predictability of upcoming bouts (odds ratio [OR] = 4.0; 95% confidence interval [CI] 1.7-9.6). In sub-study 2, we found two categories of PCSs were associated with the response to verapamil: sleep alteration (OR = 2.5 [95% CI = 1.3-4.8], p = 0.004) and ≥ 1 cranial autonomic symptoms (OR = 2.7 [95% CI = 1.4-5.1], p = 0.003). CONCLUSION: PCSs were very common in CH and could be used to predict upcoming bouts. Different symptom categories of PCSs may have different clinical implications.

Neurological and Systemic Pitfalls in the Diagnosis of Cluster Headaches: A Case-Based Review.

PURPOSE OF REVIEW: To describe different pitfalls in the diagnosis of primary cluster headaches (CHs) with the guidance of seven case vignettes. RECENT FINDINGS: The question of whether primary CHs and migraines are totally different entities has been long debated. Autonomic features can be detected in as many as 60% of migraine patients. Although some genetic similarities have been found, CACNA1A mutations have not been detected among CH patients with hemimotor aura in contrast to hemiplegic migraine. Recently, functional MRI studies have shown that the left thalamic network was the most discriminative MRI feature in distinguishing migraine from CH patients. Compared to migraine, CH patients showed decreased functional interaction between the left thalamus and cortical areas mediating interception and sensory integration. However, clinically the most significant feature had been the restlessness and agitation seen during headache attacks patients with CHs. This feature is also important in distinguishing cluster patients from other patients having other trigeminal autonomic cephalalgias except for a subset of patients with hemicrania continua. CH is an important member of the group of headache disorders characterized by their association with one or more autonomic features in the trigeminal nerve distribution and termed Trigeminal Autonomic Cephalalgias (TACs). Although CH is a relatively rare condition, judged by the distress it generally causes to the affected individual, early diagnosis and institution of appropriate therapy seem mandatory. Correct diagnosis of CHs needs avoidance of pitfalls. Such pitfalls generally include differentiation from migraine, differentiation from other side locked headache disorders, from other trigeminal autonomic cephalalgias (TACs), and lastly, recognition of rare presentations of cluster-like manifestations with hemiplegic aura and simulating trigeminal and glossopharyngeal neuralgias. Differentiation between primary and symptomatic CHs related to sellar pathologies and systemic medical conditions is of equal importance. In the present review such issues are discussed with the assistance of seven case vignettes.

Smoking and cluster headache presentation and responsiveness to treatment.

BACKGROUND: Though an association between cluster headache (CH) and smoking has been postulated, data from the Middle East region is scarce. AIM OF WORK: To study the relationship between smoking and CH clinical characteristics and responsiveness to therapy in Egypt. METHODOLOGY: This was a prospective cohort hospital-based study conducted on patients with episodic and chronic CH in a tertiary headache clinic in Egypt during the period between 2019 and 2023. Patients were consecutively recruited at the time of their presentation and were followed up for two weeks after initiation of prophylactic treatment and steroids (as transitional therapy). RESULTS: Of 172 patients with CH recruited, 144 (83.7%) were smokers. Twenty-eight patients (16.3%) had chronic CH. The mean age was 42.08 ± 10.93 (20-66) years, and 131 (76.2%) were males. Smokers had a significantly higher median number of cluster bouts in the past five years (3.0 (IQR2.0-4.0) versus 2.0 (IQR 1.0-2.0)) and worse HIT-6 scores [51.0 (44.0-59.75) versus 41.0 (38.0-41.75)] than non-smokers (p < 0.001). The number of cluster bouts in the past five years was positively correlated with the smoking index (r = 0.249 (p = 0.006) and the smoking duration (in years) (r = 0.392 (p < 0.001)). HIT-6 scores were significantly correlated with the age at smoking onset (r=-0.190, = 0.023), smoking index (r = 0.519, p < 0.001), smoking duration (r = 0.611, p < 0.001), and number of cigarettes consumed per day (r = 0.392, p < 0.001). CONCLUSION: Smoking is significantly correlated with the daily frequency of CH attacks, the frequency of CH bouts in the past five years, and the HIT-6 scores among our cohort.

Disability in cluster headache is more than attack frequency - results from and validation of the English version of the Cluster Headache Impact Questionnaire (CHIQ).

BACKGROUND: Cluster headache (CH) is associated with high disability. The Cluster Headache Impact Questionnaire (CHIQ) is a short, disease-specific disability questionnaire first developed and validated in German. Here, we validated the English version of this questionnaire. METHODS: The CHIQ was assessed together with nonspecific headache-related disability questionnaires in CH patients from a tertiary headache center and an American self-help group. RESULTS: 155 active episodic and chronic CH patients were included. The CHIQ showed good internal consistency (Cronbach's α = 0.91) and test-retest reliability (ICC = 0.93, n = 44). Factor analysis identified a single factor. Convergent validity was shown by significant correlations with the Headache Impact Test™ (HIT-6™, ρ = 0.72, p < 0.001), the Hospital Anxiety and Depression Scale (HADS depression: ρ = 0.53, HADS anxiety: ρ = 0.61, both p < 0.001), the Perceived Stress Scale (PSS-10, ρ = 0.61, p < 0.001) and with CH attack frequency (ρ = 0.29, p < 0.001). Chronic CH patients showed the highest CHIQ scores (25.4 ± 7.9, n = 76), followed by active episodic CH and episodic CH patients in remission (active eCH: 22.2 ± 8.7, n = 79; eCH in remission: 14.1 ± 13.1, n = 127; p < 0.001). Furthermore, the CHIQ was graded into 5 levels from "no to low impact" to "extreme impact" based on the patients' perception. Higher CHIQ grading was associated with higher attack and acute medication frequency, HIT-6™, HADS and PSS scores. CONCLUSION: The English version of the CHIQ is a reliable, valid, and disease-specific patient-reported outcome measure to assess the impact of headaches on CH patients.

Recent advances in diagnosing, managing, and understanding the pathophysiology of cluster headache.

Cluster headache, characterised by attacks of severe, recurrent, unilateral headache and ipsilateral cranial autonomic symptoms, remains a primary headache with an elusive pathophysiology. Recent advances have introduced effective treatments and broadened understanding of the clinical features of cluster headache. These features are similar in patients globally, but regional differences in prevalence and burden exist. International collaborations have led to identification of eight genetic loci associated with cluster headache. The pathophysiological mechanisms are still not fully understood but recent studies show that targeting the trigeminal autonomic reflex by neurostimulation, or targeting the neuropeptide calcitonin gene-related peptide (CGRP), might lessen the attack burden. The US Food and Drug Administration has approved galcanezumab, a monoclonal antibody targeting CGRP, as the first specific preventive treatment for episodic cluster headache. However, a preventive effect was not replicated in chronic cluster headache, and the European Medicines Agency did not approve galcanezumab, restricting its availability in Europe. Owing to the low prevalence of cluster headache, continued collaboration through multicentre clinical trials and data sharing will be imperative for further breakthroughs in understanding and management.

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.

Reduced plasma calcitonin gene-related peptide level identified in cluster headache: A prospective and controlled study.

BACKGROUND: The role of calcitonin gene-related peptide (CGRP) in the cyclic pattern of cluster headache is unclear. To acquire biological insight and to comprehend why only episodic cluster headache responds to CGRP monoclonal antibodies, we examined whether plasma CGRP changes between disease states (i.e. bout, remission and chronic) and controls. METHODS: The present study is a prospective case-control study. Participants with episodic cluster headache were sampled twice (bout and remission). Participants with chronic cluster headache and controls were sampled once. CGRP concentrations were measured in plasma with a validated radioimmunoassay. RESULTS: Plasma was collected from 201 participants diagnosed with cluster headache according to the International Classification of Headache Disorders, 3rd edition, and from 100 age- and sex-matched controls. Overall, plasma CGRP levels were significantly lower in participants with cluster headache compared to controls (p < 0.05). In episodic cluster headache, CGRP levels were higher in bout than in remission (mean difference: 17.1 pmol/L, 95% confidence interval = 9.8-24.3, p < 0.0001). CGRP levels in bout were not different from chronic cluster headache (p = 0.266). CONCLUSIONS: Plasma CGRP is unsuitable as a diagnostic biomarker of cluster headache or its disease states. The identified reduced CGRP levels suggest that CGRPs role in cluster headache is highly complex and future investigations are needed into the modulation of CGRP and its receptors.

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.

Patients with chronic cluster headache may show reduced activity energy expenditure on ambulatory wrist actigraphy recordings during daytime attacks.

OBJECTIVE: To investigate the changes in activity energy expenditure (AEE) throughout daytime cluster headache (CH) attacks in patients with chronic CH and to evaluate the usefulness of actigraphy as a digital biomarker of CH attacks. BACKGROUND: CH is a primary headache disorder characterized by attacks of severe to very severe unilateral pain (orbital, supraorbital, temporal, or in any combination of these sites), with ipsilateral cranial autonomic symptoms and/or a sense of restlessness or agitation. We hypothesized increased AEE from hyperactivity during attacks measured by actigraphy. METHODS: An observational study including patients with chronic CH was conducted. During 21 days, patients wore an actigraphy device on the nondominant wrist and recorded CH attack-related data in a dedicated smartphone application. Accelerometer data were used for the calculation of AEE before and during daytime CH attacks that occurred in ambulatory settings, and without restrictions on acute and preventive headache treatment. We compared the activity and movements during the pre-ictal, ictal, and postictal phases with data from wrist-worn actigraphy with time-concordant intervals during non-headache periods. RESULTS: Four patients provided 34 attacks, of which 15 attacks met the eligibility criteria for further analysis. In contrast with the initial hypothesis of increased energy expenditure during CH attacks, a decrease in movement was observed during the pre-ictal phase (30 min before onset to onset) and during the headache phase. A significant decrease (p < .01) in the proportion of high-intensity movement during headache attacks, of which the majority were oxygen-treated, was observed. This trend was less present for low-intensity movements. CONCLUSION: The unexpected decrease in AEE during the pre-ictal and headache phase of daytime CH attacks in patients with chronic CH under acute and preventive treatment in ambulatory settings has important implications for future research on wrist actigraphy in CH.

Somatosensory Profiling of Patients With Cluster Headache: A Systematic Review and Meta-analysis.

The objectives were 1) to synthesize quantitative sensory testing results in cluster headache (CH) patients and to identify somatosensory differences from healthy subjects (HS), and 2) between symptomatic and asymptomatic sides in CH patients. Two independent reviewers conducted a literature search in MEDLINE, EMBASE, Web of Science, and CINAHL databases. Studies with observational designs were included. Methodological quality and risk of bias were assessed with the Newcastle Ottawa Scale. The selected studies underwent qualitative and quantitative analyses. The qualitative analysis showed inconsistent findings among multiple studies. Meta-analysis showed lower pressure pain thresholds (PPTs) on the symptomatic side of CH patients than HS in V2 (standardized mean difference [SMD] -1.01 [95% confidence interval (CI) -1.79, -.23], P = .01, I2 = 73%, n = 114), V3 (SMD -1 [95% CI -1.54, .45], P < .01, I2 = 82%, n = 354), and cervical region (SMD -1.25 [95% CI -2.07, -.44], P < .01, I2 = 84%, n = 194). Furthermore, lower PPTs than those detected in HS were found on the asymptomatic side in V3 (SMD -.77 [95% CI -1.27, -.27], P < .01, I2 = 79%, n = 354) and in the cervical region (SMD -1.13 [95% CI -1.97, -.3], P < .01, I2 = 85%, n = 194). However, no differences were found in V1 or the extratrigeminal points between these groups. No significant changes were found between symptomatic and asymptomatic sides in trigeminal and extratrigeminal regions. Mechanical hyperalgesia in the trigemino-cervical region of patients with CH could suggest the presence of central pain mechanisms. These results are of clinical relevance because their presence could be associated with a poorer prognosis, chronification, and treatment response. PERSPECTIVE: This study provides consistent findings on the somatosensory profile characterizing patients with CH. Clinicians should assess PPTs and other quantitative sensory testing variables in the trigeminal and extratrigeminal (cervical) regions.

An atypical survey in a cluster headache patient: A case report.

Cluster headache is a rare, severe headache associated with hypothalamic dysfunction or sleep cycles. It is classified in the primary headache group in The International Classification of Headache Disorders-3-2018 (ICHD-3-2018). In this case report, we present a 62-year-old male patient whose cluster headache showed a five times longer remission interval after dental implant treatment and ceased for more than two years following cardiac stent therapy.

Translating the Cluster Headache Quality of Life Questionnaire (CHQ) from English to Dutch with the TRAPD method.

OBJECTIVE: Cluster headache is associated with a decreased quality of life (QoL). The increased focus on patient-reported outcome measures (PROMS) has led to the creation of a tailored Cluster Headache Quality of Life scale (CHQ). Our objective was to create and authenticate a Dutch version of the CHQ (CHQ-D). METHODS: The TRAPD model (Translation, Review, Adjudication, Pretesting, Documentation) was used to translate the CHQ from English to Dutch and ensure cross-cultural adaption. Pre-testing was performed in n = 31 participants, and validity was in a new sample of n = 40 participants who completed the CHQ twice at a 2-day interval. Intraclass correlation coefficient (ICC) and Cronbach's alpha were used to assess the validity and reproducibility of the CHQ-D. RESULTS: To produce the CHQ-D, we made five modifications based on pretesting. Participants finished the questionnaire in a median time of 10 min (IQR:10.0, 17.5) and 90% within 20 min. The majority of participants (74.2%) did not find it burdensome at all. The reliability of the CHQ-D was excellent (Cronbach's alpha: 0.94; ICC: 0.94). CONCLUSION: The CHQ-D is a valid and practical instrument for QoL in individuals with cluster headache. We aim to use CHQ-D as PROM in clinical research in the Netherlands to enforce international collaborations and comparisons of studies.

Biomarkers in cluster headache: A systematic review.

OBJECTIVE: To systematically investigate previously examined biomarkers in blood, urine, cerebrospinal fluid, tear fluid, and saliva of patients with cluster headache. BACKGROUND: Cluster headache is a condition with extensive clinical challenges in terms of diagnosis and treatment. Identification of a biomarker with diagnostic implications or as a potential treatment target is highly warranted. METHODS: We conducted a systematic review including peer reviewed full text of studies that measured biochemical compounds in either blood, urine, cerebrospinal fluid, tear fluid, or saliva of patients with cluster headache diagnosed after the implementation of the International Classification of Headache Disorders (1988) written in English, Danish, Swedish, or Norwegian. Inclusion required a minimum of five participants. The search was conducted in PubMed and EMBASE, in September 2022, and extracted data were screened by two authors. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for reporting systematic reviews were followed. The Newcastle-Ottawa Scale was used to assess the risk of bias in case-controlled studies. RESULTS: We included 40 studies involving 832 patients with cluster headache and 872 controls, evaluating 80 potential biomarkers. The risk of bias for case-controlled studies was a median of 6 (range: 3-8) and 20 studies out of 40 (50%) were of fair or good quality. Most studies were identified within three groups: hypothalamic-regulated hormones, inflammatory markers, and neuropeptides. Among the hypothalamic hormones, cortisol was the most frequently investigated (N = 7) and was elevated in cluster headache in most of the studies. The most frequently examined inflammatory marker was interleukin 1 (N = 3), but findings were divergent. Calcitonin gene-related peptide was the most investigated neuropeptide (N = 9) and all studies found increased levels during attacks. CONCLUSION: Biomarker findings have been inconsistent and widely non-specific for cluster headache, which explains why none of the previous studies succeeded in identifying a unique biomarker for cluster headache, but instead contributed to substantiating the underlying pathophysiologic mechanisms. Several of the examined biomarkers could hold promise as markers for disease activity but are unfit for a clear distinction from both controls and other headaches.

Pediatric Cluster Headache Case Series: Symptomatic Cases and the Migraine Relationship.

BACKGROUND: Current criteria help differentiate cluster headache from migraine. However, children may have overlapping features making it difficult to distinguish the 2 conditions, which may delay diagnosis. Differentiating cluster headache from migraine is important regarding treatment as well as diagnostic workup of secondary headache etiologies. METHODS: Cases at a single pediatric children's hospital from 2015 to 2023 diagnosed with cluster headache before the age of 18 years were reviewed. RESULTS: Twenty-five cases were identified of which 22 cases met criteria for either chronic, episodic, or probable cluster headache. Three cases were diagnosed with cluster headache by their provider, but documentation was insufficient to meet criteria for cluster headache. There were 16 females and 9 males between ages 6 and 17 years. Five cases were identified as symptomatic, 2 cases as chronic, 7 cases as episodic, and 13 cases as probable cluster headache. Symptomatic etiologies include Graves disease, optic neuritis, prolactinoma, hypothalamic pilocytic astrocytoma with carotid stenosis, and congenital right eye blindness. Migrainous features were common, including 76% with nausea, 36% with vomiting, 68% with photophobia, and 56% with phonophobia. Patients with cluster headache also had an independent diagnosis of migraine in 64%. CONCLUSION: Children with cluster headache have a high frequency of migrainous symptoms and co-occurrent diagnosis of migraine. A careful history may differentiate cluster headache from migraine and treated accordingly. Children with cluster headache features should undergo screening for secondary causes with appropriate imaging and other studies. Except for prolactinoma, the symptomatic associations noted in this case series have not been reported before.

A prospective open label 2-8 year extension of the randomised controlled ICON trial on the long-term efficacy and safety of occipital nerve stimulation in medically intractable chronic cluster headache.

BACKGROUND: We demonstrated in the randomised controlled ICON study that 48-week treatment of medically intractable chronic cluster headache (MICCH) with occipital nerve stimulation (ONS) is safe and effective. In L-ICON we prospectively evaluate its long-term effectiveness and safety. METHODS: ICON participants were enrolled in L-ICON immediately after completing ICON. Therefore, earlier ICON participants could be followed longer than later ones. L-ICON inclusion was stopped after the last ICON participant was enrolled in L-ICON and followed for ≥2 years by completing six-monthly questionnaires on attack frequency, side effects, subjective improvement and whether they would recommend ONS to others. Primary outcome was the change in mean weekly attack frequency 2 years after completion of the ICON study compared to baseline. Missing values for log-transformed attack-frequency were imputed for up to 5 years of follow-up. Descriptive analyses are presented as (pooled) geometric or arithmetic means and 95% confidence intervals. FINDINGS: Of 103 eligible participants, 88 (85%) gave informed consent and 73 (83%) were followed for ≥2 year, 61 (69%) ≥ 3 year, 33 (38%) ≥ 5 years and 3 (3%) ≥ 8.5 years. Mean (±SD) follow-up was 4.2 ± 2.2 years for a total of 370 person years (84% of potentially 442 years). The pooled geometric mean (95% CI) weekly attack frequency remained considerably lower after one (4.2; 2.8-6.3), two (5.1; 3.5-7.6) and five years (4.1; 3.0-5.5) compared to baseline (16.2; 14.4-18.3). Of the 49/88 (56%) ICON ≥50% responders, 35/49 (71%) retained this response and 15/39 (38%) ICON non-responders still became a ≥50% responder for at least half the follow-up period. Most participants (69/88; 78% [0.68-0.86]) reported a subjective improvement from baseline at last follow-up and 70/88 (81% [0.70-0.87]) would recommend ONS to others. Hardware-related surgery was required in 44/88 (50%) participants in 112/122 (92%) events (0.35 person-year-1 [0.28-0.41]). We didn't find predictive factors for effectiveness. INTERPRETATION: ONS is a safe, well-tolerated and long-term effective treatment for MICCH. FUNDING: The Netherlands Organisation for Scientific Research, the Dutch Ministry of Health, the NutsOhra Foundation from the Dutch Health Insurance Companies, and Medtronic.

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.