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Objective This study was undertaken to identify susceptibility loci for cluster headache and obtain insights into relevant disease pathways. Methods We carried out a genome-wide association study, where 852 UK and 591 Swedish cluster headache cases were compared with 5,614 and 1,134 controls, respectively. Following quality control and imputation, single variant association testing was conducted using a logistic mixed model for each cohort. The 2 cohorts were subsequently combined in a merged analysis. Downstream analyses, such as gene-set enrichment, functional variant annotation, prediction and pathway analyses, were performed. Results Initial independent analysis identified 2 replicable cluster headache susceptibility loci on chromosome 2. A merged analysis identified an additional locus on chromosome 1 and confirmed a locus significant in the UK analysis on chromosome 6, which overlaps with a previously known migraine locus. The lead single nucleotide polymorphisms were rs113658130 (p = 1.92 x 10(-17), odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.37-1.66) and rs4519530 (p = 6.98 x 10(-17), OR = 1.47, 95% CI = 1.34-1.61) on chromosome 2, rs12121134 on chromosome 1 (p = 1.66 x 10(-8), OR = 1.36, 95% CI = 1.22-1.52), and rs11153082 (p = 1.85 x 10(-8), OR = 1.30, 95% CI = 1.19-1.42) on chromosome 6. Downstream analyses implicated immunological processes in the pathogenesis of cluster headache. Interpretation We identified and replicated several genome-wide significant associations supporting a genetic predisposition in cluster headache in a genome-wide association study involving 1,443 cases. Replication in larger independent cohorts combined with comprehensive phenotyping, in relation to, for example, treatment response and cluster headache subtypes, could provide unprecedented insights into genotype-phenotype correlations and the pathophysiological pathways underlying cluster headache. ANN NEUROL 2021

Migraine is a disabling primary headache disorder that directly affects more than one billion people worldwide. Despite its widespread prevalence, migraine remains under-diagnosed and under-treated. To support clinical decision-making, we convened a European panel of experts to develop a ten-step approach to the diagnosis and management of migraine. Each step was established by expert consensus and supported by a review of current literature, and the Consensus Statement is endorsed by the European Headache Federation and the European Academy of Neurology. In this Consensus Statement, we introduce typical clinical features, diagnostic criteria and differential diagnoses of migraine. We then emphasize the value of patient centricity and patient education to ensure treatment adherence and satisfaction with care provision. Further, we outline best practices for acute and preventive treatment of migraine in various patient populations, including adults, children and adolescents, pregnant and breastfeeding women, and older people. In addition, we provide recommendations for evaluating treatment response and managing treatment failure. Lastly, we discuss the management of complications and comorbidities as well as the importance of planning long-term follow-up. © 2021, The Author(s).

The Aids to Management are a product of the Global Campaign against Headache, a worldwide programme of action conducted in official relations with the World Health Organization. Developed in partnership with the European Headache Federation, they update the first edition published 11 years ago. The common headache disorders (migraine, tension-type headache and medication-overuse headache) are major causes of ill health. They should be managed in primary care, firstly because their management is generally not difficult, and secondly because they are so common. These Aids to Management, with the European principles of management of headache disorders in primary care as the core of their content, combine educational materials with practical management aids. They are supplemented by translation protocols, to ensure that translations are unchanged in meaning from the English-language originals. The Aids to Management may be individually downloaded and, as is the case for all products of the Global Campaign against Headache, are available without restriction for non-commercial use.

In joint initiatives, the European Headache Federation and Lifting The Burden have described a model of structured headache services (with their basis in primary care), defined service quality in this context, and developed practical methods for its evaluation. Here, in a continuation of the service quality evaluation programme, we set out ten suggested role- and performance-defining standards for specialized headache centres operating as an integral component of these services. Verifiable criteria for evaluation accompany each standard. The purposes are five-fold: (i) to inspire and promote, or stimulate the establishment of, specialized headache centres as centres of excellence; (ii) to define the role of such centres within optimally structured and organized national headache services; (iii) to set out criteria by which such centres may be recognized as exemplary in their fulfilment of this role; (iv) to provide the basis for, and to initiate and motivate, collaboration and networking between such centres both nationally and internationally; (v) ultimately to improve the delivery and quality of health care for headache. © 2019 The Author(s).

We systematically reviewed data about the effect of exogenous estrogens and progestogens on the course of migraine during reproductive age. Thereafter a consensus procedure among international experts was undertaken to develop statements to support clinical decision making, in terms of possible effects on migraine course of exogenous estrogens and progestogens and on possible treatment of headache associated with the use or with the withdrawal of hormones. Overall, quality of current evidence is low. Recommendations are provided for all the compounds with available evidence including the conventional 21/7 combined hormonal contraception, the desogestrel only oral pill, combined oral contraceptives with shortened pill-free interval, combined oral contraceptives with estradiol supplementation during the pill-free interval, extended regimen of combined hormonal contraceptive with pill or patch, combined hormonal contraceptive vaginal ring, transdermal estradiol supplementation with gel, transdermal estradiol supplementation with patch, subcutaneous estrogen implant with cyclical oral progestogen. As the quality of available data is poor, further research is needed on this topic to improve the knowledge about the use of estrogens and progestogens in women with migraine. There is a need for better management of headaches related to the use of hormones or their withdrawal.

We systematically reviewed data about the effect of exogenous estrogens and progestogens on the course of migraine during reproductive age. Thereafter a consensus procedure among international experts was undertaken to develop statements to support clinical decision making, in terms of possible effects on migraine course of exogenous estrogens and progestogens and on possible treatment of headache associated with the use or with the withdrawal of hormones. Overall, quality of current evidence is low. Recommendations are provided for all the compounds with available evidence including the conventional 21/7 combined hormonal contraception, the desogestrel only oral pill, combined oral contraceptives with shortened pill-free interval, combined oral contraceptives with estradiol supplementation during the pill-free interval, extended regimen of combined hormonal contraceptive with pill or patch, combined hormonal contraceptive vaginal ring, transdermal estradiol supplementation with gel, transdermal estradiol supplementation with patch, subcutaneous estrogen implant with cyclical oral progestogen. As the quality of available data is poor, further research is needed on this topic to improve the knowledge about the use of estrogens and progestogens in women with migraine. There is a need for better management of headaches related to the use of hormones or their withdrawal. © 2018 The Author(s).

The diagnosis of primary headache disorders is clinical and based on the diagnostic criteria of the International Headache Society (ICHD-3-beta). However several brain conditions may mimic primary headache disorders and laboratory investigation may be needed. This necessity occurs when the treating physician doubts for the primary origin of headache. Features that represent a warning for a possible underlying disorder causing the headache are new onset headache, change in previously stable headache pattern, headache that abruptly reaches the peak level, headache that changes with posture, headache awakening the patient, or precipitated by physical activity or Valsalva manoeuvre, first onset of headache ≥50 years of age, neurological symptoms or signs, trauma, fever, seizures, history of malignancy, history of HIV or active infections, and prior history of stroke or intracranial bleeding. All national headache societies and the European Headache Alliance invited to review and comment the consensus before the final draft. The consensus recommends brain MRI for the case of migraine with aura that persists on one side or in brainstem aura. Persistent aura without infarction and migrainous infarction require brain MRI, MRA and MRV. Brain MRI with detailed study of the pituitary area and cavernous sinus, is recommended for all TACs. For primary cough headache, exercise headache, headache associated with sexual activity, thunderclap headache and hypnic headache apart from brain MRI additional tests may be required. Because there is little and no good evidence the committee constructed a consensus based on the opinion of experts, and should be treated as imperfect. OA gold

Purpose: Migraine and epilepsy are both prevalent chronic neurological disorders. The prevalence of migraine is 12% in the general adult population and 8,6% in children. However, there seems to be a higher prevalence of migraine in epilepsy patients. In this multicenter pilot study, we wanted to investigate what percentage of epilepsy patients also had a history of migraine. Method: During 4 consecutive weeks every epilepsy patient (>6 years old) seen at the consultation in 8 different neurology departments in Belgium, was interrogated about the occurrence of migraine using a specially designed questionnaire (based on the ICHD-II migraine criteria). Results: The questionnaire was completed in 397 patients. 231/397 patients were older than 17y (118M/113F), 166/397 were younger than 18y (89M/77F). The mean age of epilepsy onset was 16,5y (range 0- 76y). 34/231 (9M/25F) adult patients were diagnosed with migraine. In children this was the case in 18/166 patients (8M/10F). This diagnosis was newly made when completing the questionnaire in 7 adults and 7 children. The mean age of migraine onset was 18,4y (range 6-45). 7/52 patients had migraine with aura. 12/52 patients (23%) had at least 1 firstdegree relative with epilepsy and 23/52 (44%) had at least 1 first-degree relative with migraine. Conclusion: In this Belgian multicenter study, 15% of adult epilepsy patients and 11% of the children were diagnosed with migraine. These results suggest a higher prevalence of migraine in epilepsy patients compared to a normal population.

Introduction: Migraine is thought to be more prevalent in patients with epilepsy but limited data are available. In this Belgian multicenter study the comorbidity of migraine and epilepsy was prospectively analysed. Methods: During a 4 week period every epilepsy patient (>6 years old) from a series of Neurology departments in Belgium, was interrogated about the occurrence of migraine (based on the ICHD-II migraine criteria) using a specifically designed questionnaire. Results: In 237 patients (119F/118M; mean age: 32 years, range: 6-82) the questionnaire was completed and a full data set was available for analysis. 76/237 patients were younger than 18, 161/237 were >18 years old. Mean age of epilepsy onset was 17 years (range: 0-71). 36/237 (15%) patients with a mean age of 30 years (range: 8-72) (27F/9M) were diagnosed with migraine. In 11/36 this diagnosis was new. The mean age of migraine onset was 19 years (range: 7-45). 5 patients had migraine with aura. 10/36 patients (28%) reported to have at least 1 first degree relative with epilepsy and 16/36 (44%) to have at least 1 first degree relative with migraine. Conclusion: In this Belgian multicenter study, 15% of epilepsy patients were diagnosed with migraine. These results suggest a higher prevalence of migraine in epilepsy patients compared to the normal population.