Naratriptan in the Prophylactic Treatment of Cluster Headache

Objective To assess the efficacy, safety, and tolerability of verapamil as prophylactic therapy for patients withcluster headache, and compare its efficacy with that of prednisone.Methods Prospectively, according to the order of visit, a total of 45 patients with episodic cluster headache or chronic cluster headache were divided into verapamil treatment group (n=23, the odd) and prednisone treatment group (n=22, the even). The seizure frequency, and times of and dosage of using acesodyne were observed in the 2 groups 1 week before treatment, 1 and 2 week after treatment.Results Mean frequency of headache occurrence decreased from 8.78 to 2.52 and 1.35 times,respectively, in the first and second week of treatment in the verapamil group (P=0.000) and from 8.09 to 2.95 and 1.64 times, respectively, at the corresponding time in the prednisone group (P=0.000). Mean abortive agent consumption decreased from 8.09 to 1.65 and 0.48 pills, respectively, in the verapamil group (P=0.000) and from 7.77 to 2.59 and 1.36 pills, respectively, in the prednisone group (P=0.000) in the first and second week of treatment; no significant differences existed in the mean frequency of headache and abortive agent consumption between the 2 groups at the same time point (P＞0.05). The side effects of verapamil were mild, including dizziness, constipation and bradycardia and those ofprednisone were insomnia, increased appetite combined with weight gain and discomfort of abdomen. Conclusion Both verapamil and prednisone prophylaxis therapy for episodic and chronic cluster headache yield significant reduction in headache frequency and abortive agent consumption; choices can be made according to different situations. Key words: Cluster headache; Verapamil; Prednisone

ObjectiveTo present the first Brazilian real-world results with galcanezumab and provide a consensus expert opinion on the prophylactic treatment of cluster headache (CH) in Brazil.MethodsThe first part of the study (real-world results) was observational, prospective, uncontrolled, and descriptive. A sample of 44 consecutive patients with episodic or chronic CH were evaluated and treated in a traditional tertiary clinic from March 2020 to June 2024. The second part (consensus expert opinion) consisted of a survey completed by ten Brazilian headache clinicians with at least 25 years of clinical experience, who published at least 15 headache papers and attended at least 15 national or international headache conferences.ResultsForty-four patients (86.4% men, 13.6% women) were included. The average age was 45.9 ± 14.2 years. The diagnosis was made 27.3 ± 13.6 years after the onset of headache bouts. In 84.1% of the patients, CH was classified as episodic. Verapamil, lithium, or verapamil plus lithium were prescribed to respectively, 25%, 9.1%, and 6.8% of patients. Galcanezumab was prescribed to all and the majority (65.9%) used a dose of 300 mg once. There was a reduction in headache frequency of ≥ 50% at 3 weeks in 65.9% of patients for all doses of galcanezumab, and in 72.4% of those using galcanezumab 300 mg. Verapamil was recommended as a first-line treatment by 6 of 10 experts and a second-line treatment by the other 4 experts; galcanezumab was recommended as a first-line treatment by 4 of 10 experts and as a second-line treatment by 3 of 10 experts.ConclusionsThis study presented the first real-world data with galcanezumab in Brazilian patients with CH and showed a reduction in headache frequency in most patients. A survey of Brazilian experts not meant to represent the country’s guidelines, favored galcanezumab as either the first or the second option in prophylaxis. Collectively, these results highlighted galcanezumab’s promising efficacy as a new tool in CH patients.

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. 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. 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). 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.

To investigate the safety and efficacy of intranasal ketamine for the treatment of a single cluster headache (CH) attack. Acute treatment options for patients with CH who have an insufficient response to oxygen and triptans are limited. Intranasal ketamine has anecdotally been successful in treating a CH attack. We conducted an open-label pilot study enrolling 23 patients with chronic CH (International Classification of Headache Disorders, 3rd edition), and of these, 20 patients treated a single CH attack with intranasal ketamine. Under in-hospital observation, patients received 15mg of intranasal ketamine every 6min a maximum of five times. The primary endpoint was a 50% reduction in pain intensity within 15min after initiating treatment. The primary endpoint was not met; 15min after the first ketamine administration, the mean reduction in pain intensity was 1.1 (95% confidence interval [CI]: -0.6 to 2.7, p=0.188) on the numeric rating scale (NRS), equivalent to a 15% reduction in pain intensity. However, 30min after the first application, the pain intensity was reduced by 59% on an 11-point NRS (mean difference: 4.3, 95% CI: 2.4-6.2, p<0.001, N=16) and 11 out of 16 (69%) scored 4 or below on the NRS. Four patients received rescue medication 15min after the first ketamine application and were therefore excluded from the analysis at 30min. Half of the patients preferred ketamine to oxygen and/or sumatriptan injection. No serious adverse events were identified during the trial. Intranasal ketamine may be an effective acute treatment for CH at 30min but should be tested in a larger controlled design. Patients and physicians should be conscious of the abuse potential of ketamine.

Essential oils (EOs) with pro-convulsant properties are known to cause seizures and may worsen migraine. Here we report five cases of cluster headache (CH) secondary to the usage of toothpastes containing pro-convulsant EOs. Patients were identified from the headache clinics of three tertiary care hospitals in south India. Detailed history, examination, and brain magnetic resonance imaging were done in all patients. CH was diagnosed according to the International Classification of Headache Disorders, 3rd edition. Descriptive statistics were used to analyze data. We had five cases of EO-related CH (EORCH), from February 2020 to August 2021; three females and two males, with age ranging from 19 to 54 years. Three had new onset CH, while two had previous cluster attacks which had become refractory to medications for the past 1 year. The toothpastes contained EOs of camphor, eucalyptus, sage, thujone, clove, and fennel in various combinations. These toothpastes were used for a period of at least 3 months in those with new onset CH and for 12 months or more by those with chronic CH. After stopping the usage of these toothpastes, the CH attacks resolved completely within 5-10 days in all patients. In one patient we re-challenged with the same toothpaste and got the CH attack after a period of 2 months. None of the patients had recurrence of CH attacks at follow-up, ranging from 1 to 2 years. EOs with pro-convulsive properties may trigger and sustain CH. Physicians may consider inquiring about the exposure to these pro-convulsant EOs in patients with CH and may consider advising the discontinuation of products like toothpastes containing them as a possible means of CH remission.

BackgroundTriptans are effective for immediate relief of episodic cluster headache (CH) but do not reduce the frequency of attacks. Intravenous bolus injection of corticosteroids like methylprednisolone (MP) has been reported to decrease the frequency of CH attacks. We validated the prophylactic efficacy of MP pulse therapy by monitoring CH recurrence over several years following treatment of six consecutive male patients (mean age: 38.8 years, range: 26–54 years) afflicted by frequent (often daily) CH attacks.FindingsTotal MP dose per infusion was 250–500 mg for five patients and 125 mg for the sixth (a diabetic). High-dose MP was administered for 2 or 3 consecutive days in hospital for the first two patients treated. The next four patients received a single bolus injection at presentation, and in some cases a second injection days later at an outpatient clinic. The first two cases treated were also prescribed daily oral prednisolone for at most 6 months while the latter four cases were not. The frequency of CH attacks was markedly reduced in all patients, with intervals between attacks ranging from 4 to 23 months. We noted no apparent adverse events following MP administration.ConclusionsHigh-dose MP therapy reduced CH attack frequency and improved patient quality of life.

Female cluster headache in the United States of America: What are the gender differences?: Results from the United States Cluster Headache Survey

Objective Calcitonin gene-related peptide (CGRP)-(receptor) monoclonal antibody (mAb) has been reported to reduce the frequency of medication overuse in patients with migraine. The present study investigated whether or not CGRP-mAb treatment shows early effectiveness for medication overuse headache (MOH) in Japan. Methods We retrospectively reviewed 34 patients with MOH who received preventive treatment with CGRP-mAb from June 2021 to October 2022. The International Classification of Headache Disorders, 3rd edition was used to diagnose MOH. This study was conducted at the Department of Neurology, Saitama Medical University. Patients were recruited from this specialized headache outpatient center. Results In total, 69 patients with migraine had newly introduced CGRP-mAb, and 34 patients had MOH (49.3%). The mean±standard deviation patient age was 44±15.5 years old. The study population included 24 women (70.6%). The types of CGRP-mAb used were galcanezumab in 16 patients (47.0%), fremanezumab in 10 (29.4%), and erenumab in 8 (23.5%). The mean disease duration was 19.6±13.1 years. The types of migraine diagnosis were chronic migraine in 28 patients (82.4%) and migraine with aura in 11 patients (32.4%). The mean number of headache days in the month before administration of CGRP-mAb was 22±7.7 days; 1 month after administration, the MHD was 16.9±9.1 days. The change in MHD was -5.7 days (22.7%), indicating significant improvement (p<0.05). Conclusion CGRP-mAb has been suggested as a preventive treatment for patients with MOH. Further investigation of the long-term efficacy of CGRP-mAb for MOH is needed.

SYNOPSISFor two years we have tested the prophylactic efficacy of budipine for the treatment of cluster headache. The open study was carried out on 27 men and 8 women. 23 patients suffered from episodic and 2 from chronic cluster headache. 7 patients had cluster‐migraine, and 3 chronic paroxysmal hemicrania. 20 patients were free of cluster headache attacks 2–6 days after beginning daily prophylactic budipine therapy with 15–60 mg. 14 patients showed a markedly decreased frequency of attacks and the intensity of persisting attacks was diminished. One patient reported only a slight improvement. There were no non‐responders to budipine therapy. 10 patients showed only mild budipine side effects. Budipine was found very effective for treatment of cluster headache.

Objective. Cluster headache (CH) may cause excruciating pain and not all patients get satisfactory help. Patient dissatisfaction with general practitioners (GPs) and neurologists, and use of complementary and alternative treatment (CAM) may reflect this. The authors studied patient satisfaction with doctors’ treatment and use of CAM in a Norwegian CH cohort. Subjects. A total of 196 subjects with a cluster headache diagnosis were identified in the registers of two neurological departments in North Norway. Design. Of these, 70 with a confirmed diagnosis according to the second edition of the International Classification of Headache Disorders (ICHD-2) completed a comprehensive questionnaire with questions concerning satisfaction with doctors’ treatment, use of CAM, and effect of both treatment regimes. Results. Satisfaction with doctors’ treatment was reported in 44/70 (63%) (GPs) and 50/70 (71%) (neurologists) while 39/70 (56%) were satisfied with both. Too long a time to diagnosis, median four years, was the most commonly reported claim regarding doctors’ treatment. Use of CAM was reported in 27/70 (39%), and 14/70 (20%) reported experience with ≥ 2 CAM. Ten patients reported benefit from CAM (37% of “CAM users”). The average cluster period was longer in CAM-users than others (p = 0.02), but CAM use was not associated with age, education, use of medication, effect of conventional treatment, duration of cluster attacks, or time to diagnosis. Conclusion. About two-thirds of CH patients were satisfied with treatment from either GPs or neurologists, and about one-third had used CAM. Despite experiencing diagnostic delay and severe pain, cluster patients seem in general to be satisfied with doctors’ conventional treatment.

BackgroundThere 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.MethodsThe 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.ResultsAmong 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).ConclusionsPAS 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.

ObjectiveInvestigate the immune system's role in cluster headache by analyzing cytokines in people with cluster headache and headache‐free controls, and explore if certain cytokines could predict a specific phenotype.MethodsWe measured 45 cytokines in adult participants from the Danish Cluster Headache Biobank in a prospective case–control setup. People with cluster headache were diagnosed according to the International Classification of Headache Disorders third‐edition. Controls were matched for age and sex.ResultsA total of 412 were analyzed deriving from 99 with chronic cluster headache, 108 with episodic cluster headache (ECH) in bout, 105 with ECH in remission, and 100 successfully matched controls. Compared with controls, 13 cytokines were altered for ECH in bout (p < 0.05), 3 in remission (p < 0.05), and 10 for chronic cluster headache (p < 0.05). Oncostatin m was significantly elevated in all 3 disease states compared with controls (p < 0.05). Overall, the investigated cytokines showed distinct patterns of alterations between chronic cluster headache and episodic cluster headache in bout and, interestingly, IL‐1β was significantly associated with having chronic cluster headache rather than episodic in bout in a logistic regression model adjusting for potential confounders (p < 0.05).InterpretationFindings show that the immune system is altered in all 3 states of cluster headache compared with controls. Oncostatin m was elevated, constituting a promising target for future studies. The distinct alterations between episodic and chronic cluster headache are striking and urges further research of the immune system in cluster headache to better understand its potential role in prediction of disease activity and treatment response. ANN NEUROL 2025;98:4–18

Headache and Sleep

According to the International Classification of Headache Disorders diagnostic criteria, the differences between migraine and cluster headache (CH) are clear. In addition to headache attack duration and pain characteristics, the symptoms accompanying headache represent the key features in a differential diagnosis of these 2 primary headache disorders. Just a few studies of patients with CH exist examining the presence of nausea, vomiting, photophobia, phonophobia, and aura, the features commonly accompanying migraine headache. The aim of this study was to determine the presence of migraine-like features (MF) in patients with CH and establish the significance of these phenomena related to other clinical features and response to treatment. One hundred and fifty-five patients with CH were studied, and 24.5% of them experienced at least one of MF during every CH attack. Nausea and vomiting were the most frequently reported MF. The clinical presentation between CH patients with and without MF was not significantly different with the exception of aggravation of pain by effort (20.6% vs 4.1%) and facial sweating (13.2% vs 0.85%), both more frequent in CH patients with MF. Inferred from the results of our study, the presence of MF in CH patients had no important influence on the diagnosis and treatment of CH patients. The major differences of these 2 primary headache disorders, attack duration, lateralization, and the nature of associated symptoms, as delineated in the International Classification of Headache Disorders, are still useful tools for effective diagnosis.

Long-term safety, tolerability, and efficacy of eptinezumab in chronic cluster headache (CHRONICLE): an open-label safety trial.