More precise phenotyping of cluster headache using prospective attack reports.

BACKGROUND AND PURPOSE: The clinical characteristics of cluster headache (CH) are based mainly on retrospective attack descriptions of 'usual' attacks, but whether these reports are reliable is uncertain. The aim was to compare retrospective and prospective attack descriptions and describe the within- and between-patient variability of attacks. METHOD: Fifty-seven CH patients underwent a semi-structured interview obtaining a retrospective account of usual CH attacks. Patients thereafter prospectively recorded the clinical characteristics of up to 10 attacks per patient in a headache diary. Four different attack characteristics were investigated: (i) severity, (ii) duration, (iii) number of autonomic symptoms and (iv) number of migrainous symptoms. Retrospective and prospective data were compared. Within- and between-patient variability of attacks was assessed. RESULTS: Retrospective attack descriptions (n = 57) were significantly longer (P = 0.046) and more severe (P < 0.0001) for untreated attacks compared with prospective reports (n = 500). The number of autonomic symptoms was significantly higher in the retrospective reports compared to the prospective reports (P < 0.0001). Within-patient variability for attack duration, pain severity and number of autonomic and migrainous symptoms was low. Compared to men, more women reported longer (P = 0.026) and more severe (P = 0.028) attacks with more migrainous symptoms (P = 0.033). CONCLUSIONS: Important differences were found between prospectively and retrospectively reported attacks with duration and severity of untreated attacks overestimated in retrospective attack descriptions. CH attacks display low within-patient variability, but the presentation of CH attacks varies between patients. The high prevalence of symptoms typically associated with migraine should raise more diagnostic awareness for CH, especially in women who are more often misdiagnosed as having migraine.

Correction to: A PRISMA-compliant systematic review of the endpoints employed to evaluate symptomatic treatments for primary headaches.

Following publication of the original article [1], we have been notified that the name of author five was spelled incorrectly as M. Ferrili, when the correct spelling is MAN Ferilli.

Disturbed sleep in cluster headache is not the result of transient processes associated with the cluster period.

BACKGROUND AND PURPOSE: Cluster headache (CH) is characterized by severe, unilateral attacks of pain and a high nocturnal attack burden. It remains unknown whether perturbations of sleep are solely present during the CH bout. Therefore, we aimed to investigate differences in sleep between the bout and remission period in patients with episodic CH and, secondly, to compare patients in the two phases with controls. METHODS: Patients with episodic CH (aged 18-65 years), diagnosed according to the International Classification of Headache Disorders 2nd edition, were admitted for polysomnography at the Danish Center for Sleep Medicine in bout and in remission. The macrostructure of sleep, including arousals, breathing parameters, limb movements and periodic limb movements, was compared with 25 age-, sex- and body mass index-matched healthy controls. RESULTS: There were no differences in any of the sleep parameters for patients in bout (n = 32) compared with patients in remission (n = 23). Attacks were unrelated to sleep stages, presence of apnea episodes, periodic limb movements, limb movements and arousals. In bout, patients had longer sleep latency (18.8 vs. 11.7 min, P < 0.05) and rapid eye movement sleep latency (1.7 vs. 1.2 h, P < 0.05) than controls and sleep efficiency was lower (82.5% vs. 86.5%, P < 0.05). Patients in remission only had a longer sleep latency compared with controls (17.5 vs. 11.7 min, P < 0.01). CONCLUSIONS: The results support the presence of a continuing or slowly recovering disturbance of sleep outside the bout rather than a disturbance occurring secondary to attacks. Further, we confirm that there is no relation between CH attacks and specific sleep stages or between CH and breathing parameters.

A PRISMA-compliant systematic review of the endpoints employed to evaluate symptomatic treatments for primary headaches.

BACKGROUND: Primary headache are prevalent and debilitating disorders. Acute pain cessation is one of the key points in their treatment. Many drugs have been studied but the design of the trials is not usually homogeneous. Efficacy of the trial is determined depending on the selected primary endpoint and usually other different outcomes are measured. We aim to critically appraise which were the employed outcomes through a systematic review. METHODS: We conducted a systematic review of literature focusing on studies on primary headache evaluating acute relief of pain, following the PRISMA guideline. The study population included patients participating in a controlled study about symptomatic treatment. The comparator could be placebo or the standard of care. The collected information was the primary outcome of the study and all secondary outcomes. We evaluated the studied drug, the year of publication and the type of journal. We performed a search and we screened all the potential papers and reviewed them considering inclusion/exclusion criteria. RESULTS: The search showed 4288 clinical trials that were screened and 794 full articles were assessed for eligibility for a final inclusion of 495 papers. The studies were published in headache specific journals (58%), general journals (21.6%) and neuroscience journals (20.4%). Migraine was the most studied headache, in 87.8% studies, followed by tension type headache in 4.7%. Regarding the most evaluated drug, triptans represented 68.6% of all studies, followed by non-steroidal anti-inflammatories (25.1%). Only 4.6% of the papers evaluated ergots and 1.6% analyzed opioids. The most frequent primary endpoint was the relief of the headache at a determinate moment, in 54.1%. Primary endpoint was evaluated at 2-h in 69.9% of the studies. Concerning other endpoints, tolerance was the most frequently addressed (83%), followed by headache relief (71.1%), improvement of other symptoms (62.5%) and presence of relapse (54%). The number of secondary endpoints increased from 4.2 (SD = 2.0) before 1991 to 6.39 after 2013 (p = 0.001). CONCLUSION: Headache relief has been the most employed primary endpoint but headache disappearance starts to be firmly considered. The number of secondary endpoints increases over time and other outcomes such as disability, quality of life and patients' preference are receiving attention.

Sleep in cluster headache - beyond a temporal rapid eye movement relationship?

BACKGROUND AND PURPOSE: Cluster headache (CH) is a primary headache disorder characterized by severe attacks of unilateral pain following a chronobiological pattern. There is a close connection with sleep as most attacks occur during sleep. Hypothalamic involvement and a particular association with rapid eye movement (REM) sleep have been suggested. Sleep in a large, well-characterized population of CH patients was investigated. METHODS: Polysomnography (PSG) was performed on two nights in 40 CH patients during active bout and one night in 25 age, sex and body mass index matched controls in hospital. Macrostructure and other features of sleep were analyzed and related to phenotype. Clinical headache characterization was obtained by semi-structured interview. RESULTS: Ninety-nine nights of PSG were analyzed. Findings included a reduced percentage of REM sleep (17.3% vs. 23.0%, P = 0.0037), longer REM latency (2.0 vs. 1.2 h, P = 0.0012) and fewer arousals (7.34 vs. 14.1, P = 0.003) in CH patients. There was no difference in prevalence of sleep apnea between patients (38%) and matched controls (32%, P = 0.64) although the apnea index in patients was numerically higher (mean apnea-hypopnea index 10.75 vs. 4.93). No temporal association between nocturnal attacks (n = 45) and particular sleep stages was observed. CONCLUSIONS: To date, this is the largest study of sleep in CH. It is demonstrated that REM sleep is affected which is in line with our current understanding of CH and hypothalamic involvement in the regulation of this sleep stage. Further, fewer arousals were found in CH patients but no association between apnea events or specific sleep stages. The findings support a central role of the hypothalamus and arousal systems in CH.

Sleep and chronobiology in cluster headache.

BACKGROUND AND AIM: Cluster headache (CH) is the headache disorder with the strongest chronobiological traits. The severe attacks of pain occur with diurnal and annual rhythmicity but the precise rhythm and involvement of potential zeitgebers is unknown. Patients complain of poor sleep quality yet this has never been studied. We investigated triggers, rhythms, sleep quality and chronotypes in CH. METHODS: Patients and controls completed questionnaires and structured interviews composed of new and previously validated parts including the Pittsburgh Sleep Quality Index (PSQI) and Morningness-Eveningness Questionnaire (MEQ). Patients were characterized by a CH index, a unified measure of headache burden. RESULTS: A total of 275 CH patients and 145 matched controls were included. The most common trigger was sleep (80%) and a relationship between clusters and daylight was identified. Of the patients, 82.2% reported diurnal and 56% annual rhythmicity. Patients reported impaired sleep quality (PSQI) (p < 0.0001) and an inverse relationship between time passed since last attack and sleep quality was identified (p < 0.0001). The CH index was positively related to the PSQI (p < 0.0001). CONCLUSION: Diurnally, CH exhibits a relationship with night-time and annually with daylight hours. Patients' sleep quality is reduced compared with controls. Results suggest a complex relationship as sleep quality improves between clusters, but remains pathological.

Sleep in trigeminal autonomic cephalagias: a review.

PURPOSE OF REVIEW: Sleep and cluster headache (CH) are believed to be interconnected but the precise relation to the other trigeminal autonomic cephalalgias (TACs) is uncertain and complex. A better understanding of these relations may eventually lead to a clarification of the underlying mechanisms and eventually to more effective therapeutic regimens. This review aims to evaluate the existing literature on the subject of TACs and sleep. An association between episodic CH and distinct macrostructural sleep phases, especially the relation to rapid eye movement (REM) sleep, has been described in some older studies but could not be confirmed in other, more recent studies. Investigations into the microstructure of sleep in these patients are lacking. Only a few case reports exist on the relation between sleep and other TACs. SUMMARY: Recent studies do not find an association between CH and REM sleep. One older study suggests chronic paroxysmal hemicranias may be locked to REM sleep but otherwise the relation is unknown. Reports indicate that CH and obstructive sleep apnoea are associated in some individuals but results are diverging. Single cases show improvement of CH upon treatment of sleep apnoea, but the causal relationship remains in question. Other TACs are probably not connected to sleep and strictly nocturnal attacks should prompt investigations for secondary causes. The relation between CH and sleep is, however, fascinating and detailed sleep studies in carefully diagnosed patients are warranted.

Cluster headache and sleep, is there a connection? A review.

PURPOSE OF REVIEW: Sleep and the chronobiological disease cluster headache are believed to be interconnected. Despite efforts, the precise nature of the relationship remains obscured. A better understanding of this relation may lead to more effective therapeutic regimes for patients suffering from this debilitating disease. This review aims to evaluate the existing literature on the subject of cluster headache and sleep. LATEST FINDINGS: Several previous studies describe an association between episodic cluster headache and distinct macrostructural sleep phases. This association was not confirmed in a recent study of seven episodic cluster headache patients, but it was suggested that further studies into the correlation between cluster headache attacks and the microstructure of sleep are relevant. The connection between cluster headache and the hypocretins is currently under investigation. SUMMARY: There is evidence in favour of an association between episodic cluster headache and REM sleep whereas no such relation to chronic cluster headache has been reported. Particular features in the microstructure of sleep and arousal mechanisms could play a role in the pathogenesis of cluster headache. Reports indicate that cluster headache and obstructive sleep apnoea are associated. Single cases show improvement upon treatment of sleep apnoea, but the causal relationship remains in question.