Randomized controlled studies evaluating Topiramate, Botulinum toxin type A, and mABs targeting CGRP in patients with chronic migraine and medication overuse headache: A systematic review and meta-analysis.

BACKGROUND: This systematic review focuses on chronic migraine patients with medication overuse headache using, respectively, topiramate, botulinum toxin type A, and human monoclonal antibodies targeting calcitonin gene-related peptide or its receptor. METHODS: A systematic search was conducted in the databases CENTRAL, MEDLINE, Embase and Web of Science until May 2022. We included randomized controlled trials reporting the outcomes of change in monthly headache/migraine days, ≥50% response rates and change in medication overuse status. Studies were excluded if response rates were not reported. Risk of bias assessment was performed using the Cochrane RoB2 tool. The quality of evidence for outcomes across included studies was evaluated according to the five factors outlined in Cochrane GRADE approach. FINDINGS: The initial search resulted in 1599 records. Following screening, 10 studies met our inclusion criteria, while seven studies with sufficient data were included in the meta-analysis. Studies assessing Botulinum toxin type A included 1139 patients and showed a mean reduction in headache frequency by 1.92 days per month compared to placebo (-1.92; 95% CI -2.68 to -1.16). Studies assessing human monoclonal antibodies included 1982 patients, and showed significant positive effect compared to placebo for all measured outcomes. The overall odds ratio for the ≥50% response rate was 2.90 (95% CI, 2.23 to 3.78). No significant difference was observed in the frequency of adverse effect for both Botulinum toxin type A and low dose of human monoclonal antibodies compared to placebo. There is currently insufficient evidence to determine the impact of topiramate in chronic migraine patients with medication overuse headache. INTERPRETATION: Botulinum toxin type A and human monoclonal antibodies targeting calcitonin gene-related peptide receptor were beneficial in reducing monthly migraine days and ≥50% response rate, but uncertainties remained for Botulinum toxin type A regarding response rate. The effect size for human monoclonal antibodies was greater with relatively lower drop-out rate. High-quality randomized trials are required to evaluate the effect of topiramate in chronic migraine patients with medication overuse headache.

The global prevalence of headache: an update, with analysis of the influences of methodological factors on prevalence estimates.

BACKGROUND: According to the Global Burden of Disease (GBD) study, headache disorders are among the most prevalent and disabling conditions worldwide. GBD builds on epidemiological studies (published and unpublished) which are notable for wide variations in both their methodologies and their prevalence estimates. Our first aim was to update the documentation of headache epidemiological studies, summarizing global prevalence estimates for all headache, migraine, tension-type headache (TTH) and headache on ≥15 days/month (H15+), comparing these with GBD estimates and exploring time trends and geographical variations. Our second aim was to analyse how methodological factors influenced prevalence estimates. METHODS: In a narrative review, all prevalence studies published until 2020, excluding those of clinic populations, were identified through a literature search. Prevalence data were extracted, along with those related to methodology, world region and publication year. Bivariate analyses (correlations or comparisons of means) and multiple linear regression (MLR) analyses were performed. RESULTS: From 357 publications, the vast majority from high-income countries, the estimated global prevalence of active headache disorder was 52.0% (95%CI 48.9-55.4), of migraine 14.0% (12.9-15.2), of TTH 26.0% (22.7-29.5) and of H15+ 4.6% (3.9-5.5). These estimates were comparable with those of migraine and TTH in GBD2019, the most recent iteration, but higher for headache overall. Each day, 15.8% of the world's population had headache. MLR analyses explained less than 30% of the variation. Methodological factors contributing to variation, were publication year, sample size, inclusion of probable diagnoses, sub-population sampling (e.g., of health-care personnel), sampling method (random or not), screening question (neutral, or qualified in severity or presumed cause) and scope of enquiry (headache disorders only or multiple other conditions). With these taken into account, migraine prevalence estimates increased over the years, while estimates for all headache types varied between world regions. CONCLUSION: The review confirms GBD in finding that headache disorders remain highly prevalent worldwide, and it identifies methodological factors explaining some of the large variation between study findings. These variations render uncertain both the increase in migraine prevalence estimates over time, and the geographical differences. More and better studies are needed in low- and middle-income countries.

If headache has any association with hypertension, it is negative. Evidence from a population-based study in Nepal.

BACKGROUND: Hypertension and headache disorders are major contributors to public ill health, linked by a long-standing but questionable belief that hypertension is a conspicuous cause of headache. In Nepal, where hypertension is common and often untreated, we assessed the substance of this belief, hypothesising that, should hypertension be a significant cause of headache, a clear positive association between these disorders would exist. METHODS: In a cross-sectional, nationwide study, trained health workers conducted face-to-face structured interviews, during unannounced home visits, with a representative sample of the Nepalese adult population (18-65 years). They applied standard diagnostic criteria for headache disorders and measured blood pressure digitally. Hypertension was defined as systolic pressure ≥140 and/or diastolic ≥90 mm Hg. RESULTS: Of 2,100 participants (59.0% female, mean age 36.4 ± 12.8 years), 317 (15.1%) had hypertension (41.0% female) and 1,794 (85.4%) had headache (61.6% female; 728 migraine, 863 tension-type headache, 161 headache on ≥15 days/month [mutually exclusive diagnoses]; 42 unclassified headaches).All headache collectively was less prevalent among hypertension cases (78.9%) than non-cases (86.6%; p = 0.001). A negative association between hypertension and all headache was demonstrated in bivariate analysis (odds ratio: 0.6 [95% Confidence interval: 0.4-0.8]; p < 0.001), but did not maintain significance in multivariate regression analysis (adjusted odds ratio: 0.8 [95% Confidence interval: 0.5-1.1]; p = 0.09). The findings were reflected, without significance, in each headache type. CONCLUSIONS: If any association exists between hypertension and headache disorders, it is negative. From the public-health perspective, headache disorders and hypertension are unrelated entities: they need distinct policies and programs for prevention, control and management.

Use of medicinal plants for headache, and their potential implication in medication-overuse headache: Evidence from a population-based study in Nepal.

BACKGROUND: In Nepal, traditional treatment using medicinal plants is popular. Whereas medication-overuse headache is, by definition, caused by excessive use of acute headache medication, we hypothesized that medicinal plants, being pharmacologically active, were as likely a cause. METHODS: We used data from a cross-sectional, nationwide population-based study, which enquired into headache and use of medicinal plants and allopathic medications. We searched the literature for pharmacodynamic actions of the medicinal plants. RESULTS: Of 2100 participants, 1794 (85.4%) reported headache in the preceding year; 161 (7.7%) reported headache on ≥15 days/month, of whom 28 (17.4%) had used medicinal plants and 117 (72.7%) allopathic medication(s). Of 46 with probable medication-overuse headache, 87.0% (40/46) were using allopathic medication(s) and 13.0% (6/46) medicinal plants, a ratio of 6.7:1, higher than the overall ratio among those with headache of 4.9:1 (912/185). Of 60 plant species identified, 49 were pharmacodynamically active on the central nervous system, with various effects of likely relevance in medication-overuse headache causation. CONCLUSIONS: MPs are potentially a cause of medication-overuse headache, and not to be seen as innocent in this regard. Numbers presumptively affected in Nepal are low but not negligible. This pioneering project provides a starting point for further research to provide needed guidance on use of medicinal plants for headache.

A universal outcome measure for headache treatments, care-delivery systems and economic analysis.

BACKGROUND: The first manuscript in this series delineated a model of structured headache services, potentially cost-effective but requiring formal cost-effectiveness analysis (CEA). We envisaged a need for a new outcome measure for this purpose, applicable to all forms of treatment, care and care-delivery systems as opposed to comparisons of single-modality treatments. CONCEPTION AND DELINEATION: A literature review confirmed the lack of any suitable established measure. We prioritised construct validity, simplicity, comprehensiveness and expression in intuitive units. We noted that pain was the key burdensome symptom of migraine and episodic tension-type headache (TTH), that pain above a certain level was disabling, that it was difficult to put economic value to pain but relatively easy to do this for time, a casualty of headache leading to lost productivity. Alleviation of pain to a non-disabling level would be expected to bring restoration of function. We therefore based the measure on time spent in the ictal state (TIS) of migraine or TTH, either as total TIS or proportion of all time. We expressed impact on health, in units of time, as TIS*DW, where DW was the disability weight for the ictal state supplied by the Global Burden of Disease (GBD) studies. If the time unit was hours, TIS*DW yielded hours lived with (or lost to) disability (HLDs), in analogy with GBD's years lived with disability (YLDs). UTILITY ASSESSMENT: Acute treatments would reduce TIS by shortening attack duration, preventative treatments by reducing attack frequency; health-care systems such as structured headache services would have these effects by delivering these treatments. These benefits were all measurable as HLDs-averted. Population-level estimates would be derived by factoring in prevalence, but also taking treatment coverage and adherence into account. For health-care systems, additional gains from provider-training (promoting adherence to guidelines and, therefore, enhancing coverage) and consumer-education (improving adherence to care plans), increasing numbers within populations gaining the benefits of treatments, would be measurable by the same metric. CONCLUSIONS: The new outcome measure expressed in intuitive units of time is applicable to treatments of all modalities and to system-level interventions for multiple headache types, with utility for CEA and for informing health policy.

Is there a causal relationship between stress and migraine? Current evidence and implications for management.

BACKGROUND: The purpose of this narrative review is to examine the literature investigating a causal relationship between stress and migraine and evaluate its implications for managing migraine. METHODS: PubMed, PsycINFO and CINAHL were searched from 1988 to August 2021, identifying 2223 records evaluating the relationship between stress and migraine. Records were systematically screened. All potentially relevant records were thematically categorized into six mechanistic groups. Within each group the most recent reports providing new insights were cited. RESULTS: First, studies have demonstrated an association of uncertain causality between high stress loads from stressful life events, daily hassles or other sources, and the incidence of new-onset migraine. Second, major stressful life events seem to precede the transformation from episodic to chronic migraine. Third, there is some evidence for changes in levels of stress as a risk factor for migraine attacks. Research also suggests there may be a reversed causality or that stress-trigger patterns are too individually heterogeneous for any generalized causality. Fourth, migraine symptom burden seems to increase in a setting of stress, partially driven by psychiatric comorbidity. Fifth, stress may induce sensitization and altered cortical excitability, partially explaining attack triggering, development of chronic migraine, and increased symptom burden including interictal symptom burden such as allodynia, photophobia or anxiety. Finally, behavioral interventions and forecasting models including stress variables seem to be useful in managing migraine. CONCLUSION: The exact causal relationships in which stress causes incidence, chronification, migraine attacks, or increased burden of migraine remains unclear. Several individuals benefit from stress-oriented therapies, and such therapies should be offered as an adjuvant to conventional treatment and to those with a preference. Further understanding the relationship between stress, migraine and effective therapeutic options is likely to be improved by characterizing individual patterns of stress and migraine, and may in turn improve therapeutics.

Structured headache services as the solution to the ill-health burden of headache: 1. Rationale and description

In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the "patient journey") with perplexing obstacles.High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary.The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded.It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses.

Biofeedback Treatment App for Pediatric Migraine: Development and Usability Study.

OBJECTIVE: The objective of this study was to develop and investigate the usability of a biofeedback treatment smartphone app for adolescent migraine sufferers. BACKGROUND: Biofeedback is effective in treating pediatric migraine. However, biofeedback is not widely used due to the necessity of a trained therapist and specialized equipment. Emerging digital technology, including smartphones and wearables, enables new ways of administering biofeedback. METHODS: In a prospective open-label development and usability study, 10 adolescent migraine sufferers used a newly developed biofeedback app with wearable sensors that measured their muscle tension, finger temperature, and heart rate. Three iterative rounds of usability testing, including a 2-week home testing period, were completed. A biofeedback algorithm, combining and optimizing the 3 physiological modalities, and several algorithms for sham-treatment were created. Usability was evaluated statistically and summarized thematically. RESULTS: Five of ten participants completed all 3 rounds of usability testing. A total of 72 biofeedback sessions were completed. Usability scoring was consistently high, with median scores ranging from 3.5 to 4.5 on a 5-point scale. The biofeedback optimization algorithm correlated excellently to the raw physiological measurements (r = 0.85, P < .001). The intervention was safe and tolerable. CONCLUSION: We developed an app for young migraine sufferers to receive therapist-independent biofeedback. The app underwent a rigorous development process as well as usability and feasibility testing. It is now ready for clinical trials.

Volume and shape of subcortical grey matter structures related to headache: A cross-sectional population-based imaging study in the Nord-Trøndelag Health Study.

BACKGROUND: The relationship between subcortical nuclei and headache is unclear. Most previous studies were conducted in small clinical migraine samples. In the present population-based MRI study, we hypothesized that headache sufferers exhibit reduced volume and deformation of the nucleus accumbens compared to non-sufferers. In addition, volume and deformation of the amygdala, caudate, hippocampus, pallidum, putamen and thalamus were examined. METHODS: In all, 1006 participants (50-66 years) from the third Nord-Trøndelag Health Survey, were randomly selected to undergo a brain MRI at 1.5 T. Volume and shape of the subcortical nuclei from T1 weighted 3D scans were obtained in FreeSurfer and FSL. The association with questionnaire-based headache categories (migraine and tension-type headache included) was evaluated using analysis of covariance. Individuals not suffering from headache were used as controls. Age, sex, intracranial volume and Hospital Anxiety and Depression Scale were used as covariates. RESULTS: No effect of headache status on accumbens volume and shape was present. Exploratory analyses showed significant but small differences in volume of caudate and putamen and in putamen shape between those with non-migrainous headache and the controls. A post hoc analysis showed that caudate volume was strongly associated with white matter hyperintensities. CONCLUSION: We did not confirm our hypothesis that headache sufferers have smaller volume and different shape of the accumbens compared to non-sufferers. No or only small differences in volume and shape of subcortical nuclei between headache sufferers and non-sufferers appear to exist in the general population.

Burden and costs of migraine in a Swedish defined patient population - a questionnaire-based study.

BACKGROUND: Migraine is a disabling, chronic neurological disease leading to severe headache episodes affecting 13.2% of the Swedish population. Migraine leads to an extensive socio-economic burden in terms of healthcare costs, reduced workforce and quality of life (QoL) but studies of the health-economic consequences in a Swedish context are lacking. The objective of this study is to map the health-economic consequences of migraine in a defined patient population in terms of healthcare consumption, production loss and QoL in Sweden. METHODS: The study is based on data from a web-based survey to members in the Swedish patients' association suffering from migraine. The survey was conducted in May 2018 and included people with migraine aged 18 years or older. The survey included questions on health resource consumption, lost production resulting from migraine-related absenteeism and presenteeism, and QoL as measured by the EuroQol 5 dimensions questionnaire (EQ-5D-5 L) and the Headache Impact Test (HIT-6). The results are presented in yearly costs per patient and losses in quality adjusted life years (QALYs). RESULTS: The results are based on answers from 630 individuals with migraine and are presented by number of migraine days per month. The total cost per patient and year increased with the number of migraine days per month (p < 0.001) and varied between approximately €5000 for those with less than 3 migraine days per month and €24,000 per year for those with 21-28 migraine days per month. Production loss represented the main part of the costs, approximately 80%. The average loss in QALYs per year also increased with the monthly number of migraine days (p = 0.023). CONCLUSIONS: Migraine leads to significant societal costs and loss of quality of life. There appears to be an unmet need and a potential for both cost savings and QoL benefits connected with a reduction in the number of migraine days.

Inverse relationship between type 1 diabetes mellitus and migraine. Data from the Nord-Trøndelag Health Surveys 1995-1997 and 2006-2008.

Aims The aim of this cross-sectional population-based study was to investigate the associations between migraine and type 1 and type 2 diabetes mellitus (DM). Methods We used data from the second (1995-1997) and third survey (2006-2008) in the Nord-Trøndelag Health Study. Analyses were made for the 26,121 participants (30-97 years of age, median 58.3 years) with known headache and DM status in both surveys, and for the 39,584 participants in the third survey (20-97 years, median 54.1 years). The diagnosis of migraine was given to those who fulfilled the questionnaire-based migraine diagnosis in the second and/or third survey. Associations were assessed using multiple logistic regression, estimating prevalence odds ratio (OR) with 95% confidence intervals (CIs). Results In the multivariate analysis of the 26,121 participants in both surveys, adjusting for age, gender, years of education, and smoking, classical type 1 DM (n = 81) was associated with a lower prevalence of any headache (OR = 0.55, 95% CI 0.34-0.88),and migraine (OR = 0.47, 95% CI 0.26-0.96) compared to those without DM (n = 24,779). Correspondingly, the merged group of classical type 1 DM and latent autoimmune diabetes of adults (LADA) (n = 153) were less likely to have migraine (OR = 0.53, 95% CI 0.31-0.91). Similarly, an inverse relationship between type 1 DM and migraine was found in analyses of 39,584 participants in the third survey. No clear association was found between headache and type 2 DM. Conclusions In this cross-sectional population-based study of mainly middle-aged participants, type 1 DM was inversely associated with headache, in particular migraine.

The effects of aerobic exercise for persons with migraine and co-existing tension-type headache and neck pain. A randomized, controlled, clinical trial.

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.

White matter hyperintensities and headache: A population-based imaging study (HUNT MRI).

OBJECTIVE: To examine the relationship between white matter hyperintensities and headache. METHODS: White matter hyperintensities burden was assessed semi-quantitatively using Fazekas and Scheltens scales, and by manual and automated volumetry of MRI in a sub-study of the general population-based Nord-Trøndelag Health Study (HUNT MRI). Using validated questionnaires, participants were categorized into four cross-sectional headache groups: Headache-free (n = 551), tension-type headache (n = 94), migraine (n = 91), and unclassified headache (n = 126). Prospective questionnaire data was used to further categorize participants into groups according to the evolution of headache during the last 12 years: Stable headache-free, past headache, new onset headache, and persistent headache. White matter hyperintensities burden was compared across headache groups using adjusted multivariate regression models. RESULTS: Individuals with tension-type headache were more likely to have extensive white matter hyperintensities than headache-free subjects, with this being the case across all methods of white matter hyperintensities assessment (Scheltens scale: Odds ratio, 2.46; 95% CI, 1.44-4.20). Migraine or unclassified headache did not influence the odds of having extensive white matter hyperintensities. Those with new onset headache were more likely to have extensive white matter hyperintensities than those who were stable headache-free (Scheltens scale: Odds ratio, 2.24; 95% CI, 1.13-4.44). CONCLUSIONS: Having tension-type headache or developing headache in middle age was linked to extensive white matter hyperintensities. These results were similar across all methods of assessing white matter hyperintensities. If white matter hyperintensities treatment strategies emerge in the future, this association should be taken into consideration.

Lifestyle factors and risk of migraine and tension-type headache. Follow-up data from the Nord-Trøndelag Health Surveys 1995-1997 and 2006-2008.

AIMS: The aim of this population-based historical cohort study was to investigate the influence of lifestyle factors on the risk of developing migraine or tension-type headache (TTH). METHODS: Data from the Nord-Trøndelag Health Study performed in 1995-1997 and 2006-2008 was used. A total of 15,276 participants without headache at baseline were included. A Poisson regression was used to evaluate the associations between lifestyle factors and risk ratios (RRs) of migraine and TTH 11 years later. Precision of the estimates was assessed by 95% confidence interval (CIs). RESULTS: Increased risk of migraine (RR 1.30, 95% CI 1.11-1.52) was found in smokers (past or current) compared to those who had never smoked. Hard physical exercise 1-2 hours per week reduced the risk of migraine (OR 0.71, 95% CI 0.54-0.94) compared to inactivity, and the risk of migraine was also lower among those who consumed alcohol (RR 0.73, 95% CI 0.57-0.94) compared to abstainers. No association was found between smoking, physical activity, alcohol use and risk of TTH. CONCLUSIONS: The main finding was that current and previous smoking was associated with increased risk of migraine, but not of TTH.

Digital Technology and Mobile Health in Behavioral Migraine Therapy: a Narrative Review.

PURPOSE OF REVIEW: This article reviews the recent research and development of electronic health (eHealth) and, in particular, mobile health (mHealth) strategies to deliver behavioral treatment for migraine. Prospects for future development and research of mobile health in migraine are suggested. RECENT FINDINGS: Advances in digital technology and mobile technology have led to an era where electronic and mobile approaches are applied to several aspects of healthcare. Electronic behavioral interventions for migraine seem to be acceptable and feasible, but efficacy measures are uncertain. Clinical trials on mHealth-based classical behavioral therapies, such as relaxation, biofeedback, and cognitive behavioral therapy are missing in the literature. Within mHealth, headache diaries are the most researched and scientifically developed. Still, there is a gap between commercially available apps and scientifically validated and developed apps. Digital technology and mobile health has not yet lived out its potential in behavioral migraine therapy. Application of proper usability and functionality designs towards the right market, together with appraisal of medical and technological recommendations, may facilitate rapid development of eHealth and mHealth, while also establishing scientific evidence.

Health-care utilization for headache disorders in Nepal: a population-based door-to-door survey.

BACKGROUND: Headache disorders are an important global public-health problem, but under-diagnosed, undertreated and under-prioritized. Deficiencies in health care for headache, present everywhere, are likely to be greater in poorly-resourced countries. This study reports on health-care utilization for headache in Nepal, a low-income country with high headache burden. METHODS: We took data from a cross-sectional, nationwide population-based door-to-door survey, with multistage cluster random sampling. Face-to-face structured interviews included enquiry into consultations with professional health-care providers (HCPs), and investigations and treatments for headache. Analysis included associations with sociodemographic variables and indices of symptom severity. RESULTS: Of 2100 participants, 1794 reported headache during the preceding year (mean age 36.1 ± 12.6 years; male/female ratio 1:1.6). Of these, 58.4% (95% CI: 56.1-60.7%) had consulted at least once in the year with HCPs at any level, most commonly (25.0%) paramedical; 15.0% had consulted pharmacists, 10.8% general physicians and 7.6% specialists (of any type). Participants with probable medication-overuse headache consulted most (87.0%), followed by those with migraine (67.2%) and those with tension-type headache (48.6%; p < 0.001). A minority (11.9%) were investigated, mostly (8.9%) by eye tests. Half (50.8%) had used conventional medications for headache in the preceding month, paracetamol being by far the most common (38.0%), and 10.3% had used herbal therapies. Consultation was positively associated with rural habitation (AOR = 1.5; p < 0.001). Proportions consulting increased in line with all indices of symptom severity. CONCLUSIONS: Although over half of participants with headache had consulted professional HCPs, this reflects demand, not quality of care. Although 7.6% had seen specialists, very few would have been headache specialists in any sense of this term. High persistent burden, with only half of participants with headache using conventional medications, and these not best chosen, suggests these consultations fell far short of meeting need. Health policy in Nepal should recognise this, since the consequences otherwise are costly: lost health, diminished productivity and damaged national economy. On a positive note, the proportions consulting suggest that capacity exists at multiple levels within the Nepalese health system. With this to build upon, structured headache services in line with international recommendations appear achievable in Nepal. Educational programmes are the essential requirement.

Prolonged migraine aura: new insights from a prospective diary-aided study.

BACKGROUND: There is limited literature on prolonged aura (PA - defined as an aura including at least one symptom for > 1 h and < 7d), and there are no prospective studies. The aim of this study is to characterize prospectively the phenotype and prevalence of PA. FINDINGS: Two hundred and twenty-four patients suffering from migraine with aura were recruited from the Headache Centers of Pavia and Trondheim. Patients prospectively described, on an ad hoc diary, each aura symptom (AS), the duration of AS and headache, and headache features. Seventy-two patients recorded three consecutive auras in their diaries. 19 (26.4%) of patients suffered at least one PA. Out of 216 recorded auras, 38 (17.6%) were PAs. We compared PAs with non-PAs with respect to 20 features; PAs were characterized by a higher number of non-visual symptoms (non-VS) (p < 0.001). No other differences were found. We obtained similar results when we compared auras with at least one symptom with a duration of > 2 h (n = 23) or > 4 h (n = 14) with the the others (n = 193 and n = 202 respectively). CONCLUSION: PAs are quite common. They do not differ from the other auras (even when their duration extends to 2 and/or 4 h) with the exception of a higher number of non-VS.

Headache following head injury: a population-based longitudinal cohort study (HUNT).

BACKGROUND: Headache is the most frequent symptom following head injury, but long-term follow-up of headache after head injury entails methodological challenges. In a population-based cohort study, we explored whether subjects hospitalized due to a head injury more often developed a new headache or experienced exacerbation of previously reported headache compared to the surrounding population. METHODS: This population-based historical cohort study included headache data from two large epidemiological surveys performed with an 11-year interval. This was linked with data from hospital records on exposure to head injury occurring between the health surveys. Participants in the surveys who had not been hospitalized because of a head injury comprised the control group. The head injuries were classified according to the Head Injury Severity Scale (HISS). Multinomial logistic regression was performed to investigate the association between head injury and new headache or exacerbation of pre-existing headache in a population with known pre-injury headache status, controlling for potential confounders. RESULTS: The exposed group consisted of 294 individuals and the control group of 25,662 individuals. In multivariate analyses, adjusting for age, sex, anxiety, depression, education level, smoking and alcohol use, mild head injury increased the risk of new onset headache suffering (OR 1.74, 95% CI 1.05-2.87), stable headache suffering (OR 1.70, 95% CI 1.15-2.50) and exacerbation of previously reported headache (OR 1.93, 95% CI 1.24-3.02). The reference category was participants without headache in both surveys. CONCLUSION: Individuals hospitalized due to a head injury were more likely to have new onset and worsening of pre-existing headache and persistent headache, compared to the surrounding general population. The results support the entity of the ICHD-3 beta diagnosis "persistent headache attributed to traumatic injury to the head".

The association between migraine and physical exercise.

BACKGROUND: There is an unmet need of pharmacological and non-pharmacological treatment options for migraine patients. Exercise can be used in the treatment of several pain conditions, including. However, what exact role exercise plays in migraine prevention is unclear. Here, we review the associations between physical exercise and migraine from an epidemiological, therapeutical and pathophysiological perspective. METHODS: The review was based on a primary literature search on the PubMed using the search terms "migraine and exercise". RESULTS: Low levels of physical exercise and high frequency of migraine has been reported in several large population-based studies. In experimental studies exercise has been reported as a trigger factor for migraine as well as migraine prophylaxis. Possible mechanisms for how exercise may trigger migraine attacks, include acute release of neuropeptides such as calcitonin gene-related peptide or alternation of hypocretin or lactate metabolism. Mechanisms for migraine prevention by exercise may include increased beta-endorphin, endocannabinoid and brain-derived neurotrophic factor levers in plasma after exercise. CONCLUSION: In conclusion, it seems that although exercise can trigger migraine attacks, regular exercise may have prophylactic effect on migraine frequency. This is most likely due to an altered migraine triggering threshold in persons who exercise regularly. However, the frequency and intensity of exercise that is required is still an open question, which should be addressed in future studies to delineate an evidence-based exercise program to prevent migraine in sufferers.

Does pain sensitivity change by migraine phase? A blinded longitudinal study.

Objective Studies suggest that pain thresholds may be altered before and during migraine headaches, but it is still debated if a central or peripheral dysfunction is responsible for the onset of pain in migraine. The present blinded longitudinal study explores alterations in thermal pain thresholds and suprathreshold heat pain scores before, during, and after headache. Methods We measured pain thresholds to cold and heat, and pain scores to 30 seconds of suprathreshold heat four times in 49 migraineurs and once in 31 controls. Sessions in migraineurs were categorized by migraine diaries as interictal, preictal (≤one day before attack), ictal or postictal (≤one day after attack). Results Trigeminal cold pain thresholds were decreased ( p = 0.014) and pain scores increased ( p = 0.031) in the ictal compared to the interictal phase. Initial pain scores were decreased ( p < 0.029), and the temporal profile showed less adaptation ( p < 0.020) in the preictal compared to the interictal phase. Hand cold pain thresholds were decreased in interictal migraineurs compared to controls ( p < 0.019). Conclusion Preictal heat hypoalgesia and reduced adaptation was followed by ictal trigeminal cold suballodynia and heat hyperalgesia. Our results support that cyclic alterations of pain perception occur late in the prodromal phase before headache. Further longitudinal investigation of how pain physiology changes within the migraine cycle is important to gain a more complete understanding of the pathogenic mechanisms behind the migraine attack.