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Background: Cluster headache is a less-prevalent primary headache disorder but is overrepresented with regards to use of health care and social services. More insight into the socioeconomic impact is required. Methods: We investigated both the personal and societal disease burden and cost in 400 patients with well-classified cluster headache according to the ICHD-criteria and 200 sex- and age matched controls. All participants completed a cross sectional questionnaire and semi-structured interview. Results: Patients with chronic cluster headache constituted 146 out of 400 (37%). Overall, restriction in personal and/or professional life was reported by 94% of patients during attack periods. Even in remission, nine times as many episodic patients rated their health as poor/very poor compared to controls (9% vs 1%, p = 0.002). For chronic patients, the odds of rating health as good/very good were ten times lower compared to controls (OR:10.10, 95%CI:5.29–18.79. p < 0.001) and three times lower compared to episodic patients in remission (OR:3.22, 95%CI:1.90–5.47, p < 0.001). Additionally, chronic cluster headache patients were 5 times more likely to receive disability pension compared to episodic (OR:5.0, 95%CI:2.3–10.9, p < 0.001). The mean direct annual costs amounted to 9,158€ and 2,763€ for chronic and episodic patients, respectively (p < 0.001). We identified a substantial loss of productivity due to absence from work resulting in a higher indirect cost of 11,809 €/year/patient in the chronic population and 3,558 €/year/patient in the episodic population. Presenteeism could not be quantified but productivity was reduced in patients by 65% in periods with attacks compared to controls. Conclusion: Cluster headache has a major negative impact on personal life, self-perceived health, and societal cost. Patients with the chronic variant are vastly more burdened. Patients with the episodic form were still markedly affected during the remission period. This study highlights the need for more effective therapy to lighten the burden on patients and society. [ABSTRACT FROM AUTHOR]

Objective: To investigate the safety and efficacy of intranasal ketamine for the treatment of a single cluster headache (CH) attack. Background: 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. Methods: 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 15 mg of intranasal ketamine every 6 min a maximum of five times. The primary endpoint was a 50% reduction in pain intensity within 15 min after initiating treatment. Results: The primary endpoint was not met; 15 min 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, 30 min 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 15 min after the first ketamine application and were therefore excluded from the analysis at 30 min. Half of the patients preferred ketamine to oxygen and/or sumatriptan injection. No serious adverse events were identified during the trial. Conclusion: Intranasal ketamine may be an effective acute treatment for CH at 30 min but should be tested in a larger controlled design. Patients and physicians should be conscious of the abuse potential of ketamine. [ABSTRACT FROM AUTHOR]

Objective: Neuronal‐specific enolase (NSE) and protein S100B have gained considerable interest as the markers of CNS injury, glial cell activation, and/or blood‐brain barrier (BBB) disruption. No studies have investigated NSE and S100B in cluster headache (CH), but these biomarkers could contribute to the understanding of CH. Methods: Patients with episodic CH in bout (eCHa), in remission (eCHr), and chronic CH (cCH) were included in this randomized, double‐blind, placebo‐controlled, 2‐way cross‐over provocation study carried out at the Danish Headache Center. The primary endpoints included (1) differences of NSE and S100B in between groups (eCHa, eCHr, and cCH) at baseline; (2) differences over time in plasma concentrations of NSE and S100B between patient developing an attack and those who did not; (3) differences in plasma concentrations over time of NSE and S100B between active day and placebo day. Baseline findings were compared to the historical data on migraine patients and healthy controls and presented with means ± SD. Results: Nine eCHa, 9 eCHr, and 13 cCH patients completed the study and blood samples from 11 CGRP‐induced CH attacks were obtained. There were no differences in NSE levels between CH groups at baseline, but CH patients in active disease phase had higher levels compared with 32 migraine patients (9.1 ± 2.2 µg/L vs 6.0 ± 2.2 µg/L, P <.0001) and 6 healthy controls (9.1 ± 2.2 µg/L vs 7.3 ± 2.0 µg/L, P =.007). CGRP‐infusion caused no NSE changes and, but a slight, non‐significant, increase in NSE was seen in patients who reported a CGRP‐induced CH attack (2.39 µg/L, 95% Cl [−0.26, 3.85], P =.061). At baseline S100B levels in eCHa patients were higher compared to cCH patients (0.06 ± 0.02 µg/L vs 0.04 ± 0.02 µg/L, P =.018). Infusion of CGRP and CGRP‐induced attacks did not change S100B levels. Apart from induced CH‐attacks no other adverse events were noted. Conclusions: At baseline eCHa patients had higher S100B plasma levels than cCH patients and there was a slight, however not significant, NSE increase in response to CGRP‐induced CH attack. Our findings suggest a possible role of an ictal activation of glial cells in CH pathophysiology, but further studies are warranted. [ABSTRACT FROM AUTHOR]

Objective: The aim of this systematic review and meta‐analysis (SR‐MA) was to identify signaling molecule profiles and blood‐derived biomarkers in migraine and cluster headache (CH) patients. Background: Currently no migraine and CH valid biomarkers are available. Blood tests based on biomarker profiles have been used to gather information about the nervous system. Such tests have not yet been established within the primary headache field. Methods: Case‐control and case‐crossover studies investigating whole blood, plasma, and serum were identified worldwide. The qualitative synthesis focused on 9 signaling molecules (serotonin [5‐HT], calcitonin gene‐related peptide [CGRP], endothelin‐1 [ET‐1], neurokinin A, neurokinin B, neuropeptide Y, pituitary adenylate cyclase‐activating peptide 38 [PACAP‐38], substance P (SP), and vasoactive intestinal peptide) and the quantitative synthesis on 5‐HT and CGRP (≥5 comparisons available). The meta‐analysis was conducted using standard and 3‐level random effect models. Results: Fifty‐four eligible studies were identified (87.0% migraine, 9.3% CH, 3.7% migraine, and CH), and 2768 headache patients and 1165 controls included. Comparable fluctuations of 5‐HT, CGRP, ET‐1, PACAP‐38, and SP in blood were generally observed between migraine and CH. Significant findings were observed for some subgroups and strata, for example, higher interictal and ictal 5‐HT venous blood levels (ratio of means = 1.32, 95% CI: 1.08; 1.61; ratio of means = 1.23, 95% CI: 1.01; 1.49) in episodic migraine with aura with a female‐dominated case group, higher interictal CGRP blood levels in episodic migraine (ratio of means = 1.63, 95% CI: 1.18; 2.26), and chronic migraine (ratio of means = 1.89, 95% CI: 1.33; 2.68), and higher ictal CGRP blood levels (ratio of means = 1.35, 95% CI: 1.09; 1.68) in episodic migraine were observed. In most subgroups, the quantitative synthesis revealed a high degree of heterogeneity between studies in part explained by the blood sampling site, specimen source, blood specimen, and sex distribution. Other potential confounders were age, aura, study quality, menstrual cycle, and methodology (eg, storage temperature). Conclusions: Potential migraine and CH signaling molecule profiles and biomarkers were revealed. Nevertheless, the high degree of heterogeneity between studies impedes identification of valid biomarkers but allowed us to assess the presence of confounders. Consideration of the potential confounders identified in this SR‐MA might be of importance in the experimental planning of future studies. This consideration could be incorporated through establishment of specific guidelines. [ABSTRACT FROM AUTHOR]