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Objective: The objective of this study was to aggregate data for the first genomewide association study meta-analysis of cluster headache, to identify genetic risk variants, and gain biological insights., Methods: A total of 4,777 cases (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from 10 European and 1 East Asian cohorts. We first performed an inverse-variance genomewide association meta-analysis of 4,043 cases and 21,729 controls of European ancestry. In a secondary trans-ancestry meta-analysis, we included 734 cases and 9,846 controls of East Asian ancestry. Candidate causal genes were prioritized by 5 complementary methods: expression quantitative trait loci, transcriptome-wide association, fine-mapping of causal gene sets, genetically driven DNA methylation, and effects on protein structure. Gene set and tissue enrichment analyses, genetic correlation, genetic risk score analysis, and Mendelian randomization were part of the downstream analyses., Results: The estimated single nucleotide polymorphism (SNP)-based heritability of cluster headache was 14.5%. We identified 9 independent signals in 7 genomewide significant loci in the primary meta-analysis, and one additional locus in the trans-ethnic meta-analysis. Five of the loci were previously known. The 20 genes prioritized as potentially causal for cluster headache showed enrichment to artery and brain tissue. Cluster headache was genetically correlated with cigarette smoking, risk-taking behavior, attention deficit hyperactivity disorder (ADHD), depression, and musculoskeletal pain. Mendelian randomization analysis indicated a causal effect of cigarette smoking intensity on cluster headache. Three of the identified loci were shared with migraine., Interpretation: This first genomewide association study meta-analysis gives clues to the biological basis of cluster headache and indicates that smoking is a causal risk factor. ANN NEUROL 2023;94:713-726., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Preparations for the Global Campaign Against Headache done jointly with WHO started almost 25 years ago. It was officially incorporated 18 years ago. It is the story of a few dedicated individuals who, together with the World Health Organization, generated epidemiological data all over the world and made use of these data to gradually increase the position of headache disorders, until migraine became number two among all causes of years lost to disability. It is also the story of impressive development of scientific tools, their validation and use in low-income countries., Methods: Models of care for headache patients were developed that are adaptable and hence can be implemented in future throughout the world., Results: The last phase of the campaign shall use the impressive data set generated to cause real improvement in the healthcare for people with headache throughout the world. The recent World Health Organization initiative: Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders invites international organizations to collaborate, and headache is mentioned., Conclusion: This calls for the International Headache Society and all its national members and all other organizations involved in headache to work together with Lifting the Burden, the organization in charge of the Global Campaign Against Headache.

Objective: To investigate whether medication-overuse headache patients have differential DNA-methylation pattern., Methods: We collected blood samples from 120 medication-overuse headache-patients, 57 controls (29 episodic migraine patients and 28 healthy controls) in a hypothesis-generating cross-sectional case-control pilot study; 100 of the medication-overuse headache-patients were followed for six months and samples were collected at two and six months for the longitudinal methylation analyses. Blood cell proportions of leucocytes (neutrophils, NK-cells, monocytes, CD8+ and CD4+ T-cells, and B-cells) and the neutrophile-lymphocyte ratio were estimated using methylation data as a measure for immunological analysis and a cell type-specific epigenome wide association study was conducted between medication-overuse headache-patients and controls, and longitudinally for reduction in headache days/month among medication-overuse headache-patients., Results: We found a higher neutrophile-lymphocyte ratio in medication-overuse headache-patients compared to controls, indicating a higher immunological response in medication-overuse headache-patients (false discovery rate (adjusted p-value)<0.001). Reduction in headache days/month (9.8; 95% CI 8.1-11.5) was associated with lower neutrophile-lymphocyte ratio (false discovery rate adjusted p-value = 0.041).Three genes ( CORIN, CCKBR and CLDN9 ) were hypermethylated in specific cell types in medication-overuse headache-patients compared to controls. No methylation differences were associated with reduction in headache days in medication-overuse headache-patients after six months., Conclusion: This pilot study was consistent with higher immunological response in medication-overuse headache-patients which decreased with a reduction in headache days in longitudinal analysis. medication-overuse headache-patients exhibited differential methylation in innate immune cells but did not exhibit longitudinal differences with alterations in headache days. Our study creates hypotheses for further biomarker searches. ClinicalTrials.gov Identifier: NCT02993289.

Medication overuse headache (MOH) is a secondary headache disorder attributed to overuse of acute headache medications by a person with an underlying headache disorder, usually migraine or tension-type headache. MOH is common among individuals with 15 or more headache days per month. Although MOH is associated with substantial disability and reductions in quality of life, this condition is often under-recognized. As MOH is both preventable and treatable, it warrants greater attention and awareness. The diagnosis of MOH is based on the history and an unremarkable neurological examination, and is made according to the diagnostic criteria of the International Classification of Headache Disorders third edition (ICHD-3). Pathophysiological mechanisms of MOH include altered descending pain modulation, central sensitization and biobehavioural factors. Treatment of MOH includes the use of headache preventive therapies, but essential to success is eliminating the cause, by reducing the frequency of use of acute headache medication, and perhaps withdrawing the overused medication altogether. Appropriate treatment is usually highly effective, leading to reduced headache burden and acute medication consumption., (© 2023. Springer Nature Limited.)

Objective: We investigated whether telephone follow-up consultations could lead to appropriate adjustment of treatments and a higher degree of patient satisfaction among patients with migraine and tension-type headache (TTH)., Background: Migraine and TTH are disabling headache forms requiring optimized treatment., Methods: In a prospective, non-randomized, quality control study with controls comparing telephone-interview intervention (TeII) with business-as-usual (BAU) treatment, we included newly referred patients with migraine and/or TTH. The TeII group was contacted by telephone by healthcare professionals at 8 and 16 weeks after the first visit addressing headache treatment. Electronic questionnaires were sent to all participants before the first visit and after 6 months. Predefined outcomes were number of patients with change in preventive and acute medication; change in headache frequency; migraine frequency; scores from the eight-item Headache Under-Response to Treatment (HURT-8) questionnaire, Insomnia Severity Index (ISI), and Hospital Anxiety and Depression Scale (HADS); and patient satisfaction after 6 months., Results: From May 2020 to April 2021, there were 230 patients enrolled in the TeII program, whereof 96 patients were included in the analysis. For the BAU group, 91 patients with similar sex and age distribution were identified via medical-record reviews in the same period. More patients in the TeII group than in the BAU group had a change in acute medication (27/96 [28%] vs. five of 91 [6%], p < 0.001) and preventive medication (28/96 [29%] vs. 12/91 [13%], p = 0.006). Headache days per month decreased in the TeII group (-4.6, 95% confidence interval [CI] -6.5 to -2.7; p = 0.001) and the BAU group (-2.5, 95% CI -4.6 to -0.4; p = 0.018), without significant difference between the groups (p = 0.080). There was no difference in migraine frequency between the groups (TeII: 1.0 day, 95% CI, -1.3 to 1.0; BAU: 1.0 day, 95% CI, -2.5 to 0.5; p = 0.718) or HURT-8 score (TeII: 10.5, 95% CI 9.5-11.5; BAU: 13.0, 95% CI 11.7-14.2; p = 0.053). There were no changes in the ISI score (TeII: 1.0, interquartile range [IQR] 6; p = 0.152; BAU: 0.5, IQR 4.5; p = 0.824), HADS-Anxiety score (TeII: -5, IQR 5.3; p = 0.186; BAU: 1.0, IQR 4.0; p = 0.445), or HADS-Depression score (TeII: 0.0, IQR 3.0; p = 0.163; BAU: 0.0, IQR 2.0; p = 0.303) in any of the groups. There was a higher degree of patient satisfaction in the TeII group compared with the BAU group in treatment (median [IQR] score 4 [3-5] vs. 3 [3-4], p < 0.001), headache improvement (median [IQR] 3 [2-4] vs. 2 [1-3], p = 0.002), the headache program (median [IQR] 4 [3-5] vs. 3 [3-4], p < 0.001), and information (median [IQR] 4 [3-5] vs. 3 [3-4], p = 0.005)., Conclusion: Patients with migraine and/or TTH benefit from a telephone follow-up approach within the first 6 months of their treatment course in terms of more efficient treatment and higher patient satisfaction., (© 2022 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Objectives: To investigate previous treatment and clinical characteristics in migraine and tension-type headache patients at their first visit to a tertiary headache center., Methods: This was a cross-sectional study using data obtained from electronic questionnaires and medical charts. Migraine and tension-type headache patients were investigated at their first visit to the Danish Headache Center., Results: Out of 382 patients the main diagnoses of primary headaches were: 36% with episodic migraine, 43% with chronic migraine, 3% with episodic tension-type headache and 17% with chronic tension-type headache. The majority had attempted non-pharmacological treatment options such as physiotherapy (episodic migraine: 53%, chronic migraine: 68%, episodic tension-type headache: 50%, chronic tension-type headache: 65%) and acupuncture: (episodic migraine: 45%, chronic migraine: 62%, episodic tension-type headache: 17%, chronic tension-type headache: 51%). The majority of migraine patients had tried no more than one triptan (episodic migraine: 71%, chronic migraine: 66%). In total, 35% of episodic migraine and 19% of chronic migraine patients as well as 50% of episodic tension-type headache and 41% of chronic tension-type headache patients had never tried preventive medication. The headache under-response to treatment (HURT) questionnaire score was higher in chronic migraine (score 15) and chronic tension-type headache (score 16) patients than the episodic forms ( P  < 0.004)., Conclusions: Headache patients had attempted several non-pharmacological treatments prior to their first visit at a tertiary headache center in Denmark. The limited use of acute and preventive treatment before the first visit demonstrates a need for better treatment at the primary and secondary care level.

Objectives: We aimed to investigate whether coexistent self-reported neck pain influences cephalic and extracephalic pain sensitivity in individuals with migraine and tension-type headache (TTH) in relation to diagnosis and headache frequency., Methods: A population of 496 individuals completed a headache interview based on ICHD criteria, providing data collected by self-administered questionnaires, assessments of pericranial total tenderness score (TTS) and pressure pain thresholds (PPT). Stimulus-response (SR) functions for pressure vs. pain were recorded. Presence of neck pain in the past year was assessed by the self-administered questionnaire. We categorized participants by primary headache type. We also categorized participants into 3 groups by headache frequency: chronic (≥15) or episodic (<15 headache days/month) headache and controls. TTS, PPTs and the area under the SR curve were compared between subgroups using Generalized Linear Models with pairwise comparisons controlling for age and sex., Results: Individuals with chronic followed by episodic headache had higher TTS than controls (overall p≤0.001). The difference between chronic and episodic headache subgroups was significant in the group with neck pain (p≤0.001) but not in the group without neck pain. In individuals with neck pain, mean TTS was higher in coexistent headache (migraine and TTH), 23.2 ± 10.7, and pure TTH, 17.8 ± 10.3, compared to pure migraine, 15.9 ± 10.9 and no headache 11.0 ± 8.3 (overall p<0.001). Temporal and finger PPTs did not statistically differ among the chronic headache, the episodic headache and controls in individuals with and without neck pain. Temporalis and trapezius SR-functions showed that tenderness was increased in individuals with chronic headache to higher degree than in those with episodic headache, and more so in those with neck pain., Conclusions: Coexistent neck pain is associated with greater pericranial tenderness in individuals with chronic headache and to a lesser degree in those with episodic headache. Sensitization may be a substrate or consequence of neck pain and primary headache, but a longitudinal study would be needed for further clarification., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Headache disorders are disabling, with major consequences for productivity, yet the literature is silent on the relationship between headache-attributed disability and lost productivity, often erroneously regarding the two as synonymous. We evaluated the relationship empirically, having earlier found that investment in structured headache services would be cost saving, not merely cost-effective, if reductions in headache-attributed disability led to > 20% pro rata recovery of lost productivity., Methods: We used individual participant data from Global Campaign population-based studies conducted in China, Ethiopia, India, Nepal, Pakistan and Russia, and from Eurolight in Lithuania, Luxembourg and Spain. We assessed relationships in migraine and probable medication-overuse headache (pMOH), the most disabling common headache disorders. Available symptom data included headache frequency, usual duration and usual intensity. We used frequency and duration to estimate proportion of time in ictal state (pTIS). Disability, in the sense used by the Global Burden of Disease study, was measured as the product of pTIS and disability weight for the ictal state. Impairment was measured as pTIS * intensity. Lost productivity was measured as lost days (absence or < 50% productivity) from paid work and corresponding losses from household work over the preceding 3 months. We used Spearman correlation and linear regression analyses., Results: For migraine, in a linear model, we found positive associations with lost paid worktime, significant (p < 0.05) in many countries and highly significant (p < 0.001) in some despite low values of R 2 (0-0.16) due to high variance. With lost household worktime and total lost productivity (paid + household), associations were highly significant in almost all countries, although still with low R 2 (0.04-0.22). Applying the regression equations for each country to the population mean migraine-attributed disability, we found pro rata recoveries of lost productivity in the range 16-56% (> 20% in all countries but Pakistan). Analysing impairment rather than disability increased variability. For pMOH, with smaller numbers, associations were generally weaker, occasionally negative and mostly not significant., Conclusion: Relief of disability through effective treatment of migraine is expected, in most countries, to recover > 20% pro rata of lost productivity, above the threshold for investment in structured headache services to be cost saving., (© 2021. The Author(s).)

Background: Obesity confers adverse effects to every system in the body including the central nervous system. Obesity is associated with both migraine and idiopathic intracranial hypertension (IIH). The mechanisms underlying the association between obesity and these headache diseases remain unclear., Methods: We conducted a narrative review of the evidence in both humans and rodents, for the putative mechanisms underlying the link between obesity, migraine and IIH., Results: Truncal adiposity, a key feature of obesity, is associated with increased migraine morbidity and disability through increased headache severity, frequency and more severe cutaneous allodynia. Obesity may also increase intracranial pressure and could contribute to headache morbidity in migraine and be causative in IIH headache. Weight loss can improve both migraine and IIH headache. Preclinical research highlights that obesity increases the sensitivity of the trigeminovascular system to noxious stimuli including inflammatory stimuli, but the underlying molecular mechanisms remain unelucidated., Conclusions: This review highlights that at the epidemiological and clinical level, obesity increases morbidity in migraine and IIH headache, where weight loss can improve headache morbidity. However, further research is required to understand the molecular underpinnings of obesity related headache in order to generate novel treatments., (© 2021. The Author(s).)

Background: Although the European Medicines Agency and the US Food and Drug Administration have cleared several devices that use neuromodulation to provide clinical benefits in the acute or preventive treatment of migraine, the Clinical Trials Committee of the International Headache Society has not developed guidelines specifically for clinical trials of neuromodulation devices. In recognition of the distinct needs and challenges associated with their assessment in controlled trials, the Committee provides these recommendations for optimizing the design and conduct of controlled trials of neuromodulation devices for the acute and/or preventive treatment of migraine., Methods: An international group of headache scientists and clinicians with expertise in neuromodulation evaluated clinical trials involving neuromodulation devices that have been published since 2000. The Clinical Trials Committee incorporated findings from this expert analysis into a new guideline for clinical trials of neuromodulation devices for the treatment of migraine., Results: Key terms were defined and recommendations provided relative to the assessment of neuromodulation devices for acute treatment in adults, preventive treatment in adults, and acute and preventive treatment in children and adolescents. Ethical and administrative responsibilities were outlined, and a bibliography of previous research involving neuromodulation devices was created., Conclusions: Adoption of these recommendations will improve the quality of evidence regarding this important area in migraine treatment.

Background: Combined withdrawal and early preventive medication was the most effective treatment for medication overuse headache (MOH) within the first 6 months in a previous study, but results from a longer follow-up period are lacking., Objective: (1) To measure the efficacy at 1 year of three different treatment approaches to MOH; (2) to compare withdrawal and early preventives (W+P), preventives with potential withdrawal therapy after 6 months (P+pW), and withdrawal with delayed potential preventives (W+pP); and (3) to identify predictors of chronic headache after 1 year., Methods: Patients with MOH and migraine and/or tension-type headache were randomly assigned to one of the three outpatient treatments. Headache calendar and questionnaires were filled out. Primary outcome was a reduction in headache days/month after 1 year., Results: Of 120 patients, 96 completed 1-year follow-up, and all were included in our analyses. Overall headache days/month were reduced from 24.6 (23.4-25.8) to 15.0 (13.0-17.0) (p < 0.0001), and only 11/96 patients (11%) relapsed. Reduction in monthly headache days was 10.3 days (95% CI: 6.7-13.9) in the W+P group, 10.8 days (95% CI: 7.6-14) in the P+pW group, and 7.9 days (95% CI: 5.1-10.7) in the W+pP group. No significant differences in treatment effect were seen between the three groups (p = 0.377). After 1 year, 39/96 (41%) had chronic headache. Predictors of chronic headache after 1 year were higher headache frequency (aOR 1.19; 1.09-1.31), more days with acute medication (aOR 1.11; 1.03-1.19), higher pain intensity (aOR 1.04; 1.01-1.08), and depression (aOR 4.7; 1.38-18.95), whereas higher self-rated health (aOR 0.61; 0.36-0.97) and high caffeine consumption (aOR 0.40; 0.16-0.96) were predictors of a lower risk of chronic headache. No adverse events were reported., Conclusions: All treatment strategies proved effective in treating MOH with a low relapse rate. The W+P strategy leads to the fastest effect, confirming earlier treatment recommendations. Identification of predictors for chronic headache may help identify more complex patients., (© 2021 American Headache Society.)

Objectives: Tension-type headache (TTH) is the most prevalent primary headache disorder. We assessed the cross-sectional impact of TTH on health related quality of life (HRQoL) in a general population. We also examined the association of HRQoL scores with headache frequency, disability, medication overuse, poor self-rated health, psychiatric comorbidity, and pain sensitivity in individuals with TTH., Methods: A sample of 547 subjects completed a headache diagnostic interview, the SF-12 to calculate physical (PCS) and mental (MCS) health component scores, depression (major depression inventory [MDI]) and neuroticism (Eysenck Personality Questionnaire) measures. We defined the following headache diagnosis categories: pure TTH, pure migraine, and coexistent headache (TTH + migraine). Cases were further classified into chronic (≥15) or episodic (<15 headache days/month)., Results: Using generalized linear models (GLM) adjusted for age, sex and education, both PCS-12 and MCS-12 scores varied in groups distinguished by migraine and TTH status; scores were lower for individuals with coexistent headache (TTH + migraine; n=83), followed by pure TTH (n=97) and pure migraine (n=43) compared to the no headache group (n=324) (p≤0.001). In analyses considering chronicity, PCS-12 scores were lower in chronic coexistent headache followed by pure chronic TTH (CTTH), episodic migraine +/- episodic TTH (ETTH) and pure ETTH than in the no headache group (p≤0.001). MCS-12 scores were lower in pure CTTH, followed by chronic coexistent headache, episodic migraine +/- ETTH and pure ETTH compared to the no headache group (p≤0.001). Multiple regression models showed that in TTH, lower PCS-12 scores were associated with age (p=0.04), female sex (p=0.02), and poor self-rated health (p≤0.001). Lower MCS-12 scores in TTH were associated with depression (p≤0.001)., Conclusions: In a population sample, TTH, and to higher degree CTTH, are associated with decreased HRQoL., (© 2020 Sait Ashina et al., published by De Gruyter, Berlin/Boston.)

Introduction: Cephalic autonomic symptoms occur in 27‒73% of migraine patients during attacks. The role of parasympathetic activation in migraine attack initiation remains elusive. Low frequency stimulation of the sphenopalatine ganglion increases parasympathetic outflow. In this study, we hypothesized that low frequency stimulation of the sphenopalatine ganglion would provoke migraine-like attacks in migraine patients., Methods: In a double-blind randomized sham-controlled crossover study, 12 migraine patients with a sphenopalatine ganglion neurostimulator received low frequency or sham stimulation for 30 min on two separate days. We recorded headache characteristics, cephalic autonomic symptoms, ipsilateral mechanical perception and pain thresholds, mean blood flow velocity in the middle cerebral artery (V MCA ) and diameter of the superficial temporal artery during and after stimulation., Results: Five patients (42%) reported a migraine-like attack after low frequency stimulation compared to six patients (50%) after sham ( p  = 1.000). We found a significant increase in mechanical detection thresholds during low frequency stimulation compared to baseline ( p  = 0.007). Occurrence of cephalic autonomic symptoms and changes in mechanical perception thresholds, V MCA and diameter of the superficial temporal artery showed no difference between low frequency stimulation compared to sham ( p  = 0.533)., Conclusion: Low frequency stimulation of the sphenopalatine ganglion did not induce migraine-like attacks or autonomic symptoms in migraine patients. These data suggest that increased parasympathetic outflow by the sphenopalatine ganglion neurostimulator does not initiate migraine-like attacks. Study protocol: ClinicalTrials.gov registration number NCT02510742.

Objectives: Medication-overuse headache (MOH) is recognized as a biobehavioural disorder, warranting that both biological and psychological factors are targeted throughout treatment. A psychological factor of importance may be personality that could be used to tailor treatment if differences are found across headache diagnoses. The objectives were as follows: (a) To investigate if migraine patients and patients with MOH differed on personality traits, (b) To investigate if the two headache groups differed from a Danish normative sample, with respect to personality traits., Materials and Methods: The NEO-Five-Factor Inventory was completed, and an age-matched cohort of episodic migraine patients (n = 94) and MOH patients (n = 94) was included. Multivariate regression models and sex-stratified comparisons were made on patients' raw scores from five personality traits; neuroticism, extraversion, openness, agreeableness, and conscientiousness. The headache groups were also compared to personality traits from a Danish normative sample (n = 1032)., Results: MOH females obtained significantly lower scores on extraversion (24.4 ± 4.3 vs 27.1 ± 7.2, P < 0.01), openness (23.7 ± 3.9 vs 26.2 ± 6.4, P < 0.01), and conscientiousness (28.9 ± 3.7 vs 34.6 ± 5.8, P > 0.01) as compared to female migraineurs. Males showed no differences. Compared to the normative sample, both headache groups showed a lower score on extraversion (P < 0.01). Furthermore, MOH patients had statistically significant lower scores on conscientiousness while the migraine patients had a higher score., Conclusion: Results suggests some personality trait differences between migraine and MOH patients. Especially, females showed different personality traits, where the MOH females appeared more introvert and less socially orientated. If confirmed in larger studies, this information could be used in personalized treatment in clinical practice., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Complete stop of acute medication and/or migraine medication for treatment of medication-overuse headache (MOH) has previously been reported more effective in reducing headache days and migraine days per month compared with restricted intake of acute medication. However, it is unknown whether complete stop or restricted intake is the most feasible treatment for patients., Objectives: To investigate whether feasibility of withdrawal in MOH is different between complete stop of acute medication and restricted intake, and whether reductions in headache-related medication dependence, anxiety and depression differ between the treatments., Methods: Medication-overuse headache patients were included in a prospective, open-label, outpatient study and randomized to two months of withdrawal with either no analgesics or acute migraine medication (programme A) or acute medication restricted to 2 days/week (programme B). After 6 and 12 months, patients graded feasibility of withdrawal. Dependence was measured by Severity of Dependence Scale (SDS), while anxiety and depression were measured by Hospital Anxiety and Depression Scale (HADS)., Results: We included 72 MOH patients with primary migraine and/or tension-type headache. Forty-nine completed withdrawal and the SDS questionnaire at 12-month follow-up, and the feasibility of withdrawal was significantly higher in programme A compared to programme B (p < 0.001). At 12 months, the dependence was reduced by 44% in programme A compared to 26% in programme B (p = 0.053), while the anxiety score was reduced by 32% and 11%, respectively (p = 0.048)., Conclusions: Withdrawal with complete stop of acute medication was more feasible and most effective in reducing headache-related anxiety compared with restricted intake., Significance: A complete stop of all analgesics is the most effective treatment for MOH regarding reduction in headache days but has often been regarded as too challenging for patients. However, in this study, complete stop appears to be more feasible compared with restricted intake of analgesics seen from the patients' perspective., (© 2019 European Pain Federation - EFIC®.)

Small subsets of patients who fail to respond to pharmacological treatment may benefit from alternative treatment methods. In the last decade, neurostimulation is being explored as a potential treatment option for the patients with chronic, severely disabling refractory primary headaches. To alleviate pain, specific nerves and brain areas have been stimulated, and various methods have been explored: deep brain stimulation, occipital nerve stimulation, and sphenopalatine ganglion stimulation are among the more invasive ones, whereas transcranial magnetic stimulation and supraorbital nerve stimulation are noninvasive. Vagal nerve stimulation can be invasive or noninvasive, though this review included only data for noninvasive VNS. Most of these methods have been tested in small open-label patient series; recently, more data from randomized, controlled, and blinded studies are available. Although neurostimulation treatments have demonstrated good efficacy in many studies, it still has not been established as a standard treatment in refractory patients. This review analyzes the available evidence regarding efficacy and safety of different neurostimulation modalities for the treatment of chronic migraine and cluster headache., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim To evaluate aerobic exercise in migraine and co-existing tension-type headache and neck pain. Methods Consecutively recruited persons with migraine and co-existing tension-type headache and neck pain were randomized into an exercise group or control group. Aerobic exercise consisted of bike/cross-trainer/brisk walking for 45 minutes, three times/week. Controls continued usual daily activities. Pain frequency, intensity, and duration; physical fitness, level of physical activity, well-being and ability to engage in daily activities were assessed at baseline, after treatment and at follow-up. Results Fifty-two persons completed the study. Significant between-group improvements for the exercise group were found for physical fitness, level of physical activity, migraine burden and the ability to engage in physical activity because of reduced impact of tension-type headache and neck pain. Within the exercise group, significant reduction was found for migraine frequency, pain intensity and duration, neck pain intensity, and burden of migraine; an increase in physical fitness and well-being. Conclusions Exercise significantly reduced the burden of migraine and the ability to engage in physical activity because of reduced impact of tension-type headache and neck pain. Exercise also reduced migraine frequency, pain intensity and duration, although this was not significant compared to controls. These results emphasize the importance of regular aerobic exercise for reduction of migraine burden.

Background: Headache disorders are both common and burdensome but, given the many people affected, provision of health care to all is challenging. Structured headache services based in primary care are the most efficient, equitable and cost-effective solution but place responsibility for managing most patients on health-care providers with limited training in headache care. The development of practical management aids for primary care is therefore a purpose of the Global Campaign against Headache. This manuscript presents an outcome measure, the Headache Under-Response to Treatment (HURT) questionnaire, describing its purpose, development, psychometric evaluation and assessment for clinical utility. The objective was a simple-to-use instrument that would both assess outcome and provide guidance to improving outcome, having utility across the range of headache disorders, across clinical settings and across countries and cultures., Methods: After literature review, an expert consensus group drawn from all six world regions formulated HURT through item development and item reduction using item-response theory. Using the American Migraine Prevalence and Prevention Study's general-population respondent panel, two mailed surveys assessed the psychometric properties of HURT, comparing it with other instruments as external validators. Reliability was assessed in patients in two culturally-contrasting clinical settings: headache specialist centres in Europe (n = 159) and primary-care centres in Saudi Arabia (n = 40). Clinical utility was assessed in similar settings (Europe n = 201; Saudi Arabia n = 342)., Results: The final instrument, an 8-item self-administered questionnaire, addressed headache frequency, disability, medication use and effect, patients' perceptions of headache "control" and their understanding of their diagnoses. Psychometric evaluation revealed a two-factor model (headache frequency, disability and medication use; and medication efficacy and headache control), with scale properties apparently stable across disorders and correlating well and in the expected directions with external validators. The literature review found few instruments linking assessment to clinical advice or suggested actions: HURT appeared to fill this gap. In European specialist care, it showed utility as an outcome measure across headache disorders. In Saudi Arabian primary care, HURT (translated into Arabic) was reliable and responsive to clinical change., Conclusions: With demonstrated validity and clinical utility across disorders, cultures and settings, HURT is available for clinical and research purposes.

Background: The prevalence of migraine with co-existing tension-type headache and neck pain is high in the general population. However, there is very little literature on the characteristics of these combined conditions. The aim of this study was to investigate a) the prevalence of migraine with co-existing tension-type headache and neck pain in a clinic-based sample, b) the level of physical activity, psychological well-being, perceived stress and self-rated health in persons with migraine and co-existing tension-type headache and neck pain compared to healthy controls, c) the perceived ability of persons with migraine and co-existing tension-type headache and neck pain to perform physical activity, and d) which among the three conditions (migraine, tension-type headache or neck pain) is rated as the most burdensome condition., Methods: The study was conducted at a tertiary referral specialised headache centre where questionnaires on physical activity, psychological well-being, perceived stress and self-rated health were completed by 148 persons with migraine and 100 healthy controls matched by sex and average age. Semi-structured interviews were conducted to assess characteristics of migraine, tension-type headache and neck pain., Results: Out of 148 persons with migraine, 100 (67%) suffered from co-existing tension-type headache and neck pain. Only 11% suffered from migraine only. Persons with migraine and co-existing tension-type headache and neck pain had lower level of physical activity and psychological well-being, higher level of perceived stress and poorer self-rated health compared to healthy controls. They reported reduced ability to perform physical activity owing to migraine (high degree), tension-type headache (moderate degree) and neck pain (low degree). The most burdensome condition was migraine, followed by tension-type headache and neck pain., Conclusions: Migraine with co-existing tension-type headache and neck pain was highly prevalent in a clinic-based sample. Persons with migraine and co-existing tension-type headache and neck pain may require more individually tailored interventions to increase the level of physical activity, and to improve psychological well-being, perceived stress and self-rated health.

The debate on the clinical definition of refractory Chronic Migraine (rCM) is still far to be concluded. The importance to create a clinical framing of these rCM patients resides in the complete disability they show, in the high risk of serious adverse events from acute and preventative drugs and in the uncontrolled application of therapeutic techniques not yet validated.The European Headache Federation Expert Group on rCM presents hereby the updated definition criteria for this harmful subset of headache disorders. This attempt wants to be the first impulse towards the correct identification of these patients, the correct application of innovative therapeutic techniques and lastly aim to be acknowledged as clinical entity in the next definitive version of the International Classification of Headache Disorders 3 (ICHD-3 beta).