Questionnaire and structural imaging data accurately predict headache improvement in patients with acute post-traumatic headache attributed to mild traumatic brain injury.

BACKGROUND: Our prior work demonstrated that questionnaires assessing psychosocial symptoms have utility for predicting improvement in patients with acute post-traumatic headache following mild traumatic brain injury. In this cohort study, we aimed to determine whether prediction accuracy can be refined by adding structural magnetic resonance imaging (MRI) brain measures to the model. METHODS: Adults with acute post-traumatic headache (enrolled 0-59 days post-mild traumatic brain injury) underwent T1-weighted brain MRI and completed three questionnaires (Sports Concussion Assessment Tool, Pain Catastrophizing Scale, and the Trait Anxiety Inventory Scale). Individuals with post-traumatic headache completed an electronic headache diary allowing for determination of headache improvement at three- and at six-month follow-up. Questionnaire and MRI measures were used to train prediction models of headache improvement and headache trajectory. RESULTS: Forty-three patients with post-traumatic headache (mean age = 43.0, SD = 12.4; 27 females/16 males) and 61 healthy controls were enrolled (mean age = 39.1, SD = 12.8; 39 females/22 males). The best model achieved cross-validation Area Under the Curve of 0.801 and 0.805 for predicting headache improvement at three and at six months. The top contributing MRI features for the prediction included curvature and thickness of superior, middle, and inferior temporal, fusiform, inferior parietal, and lateral occipital regions. Patients with post-traumatic headache who did not improve by three months had less thickness and higher curvature measures and notably greater baseline differences in brain structure vs. healthy controls (thickness: p < 0.001, curvature: p = 0.012) than those who had headache improvement. CONCLUSIONS: A model including clinical questionnaire data and measures of brain structure accurately predicted headache improvement in patients with post-traumatic headache and achieved improvement compared to a model developed using questionnaire data alone.

Migraine and air pollution: A systematic review.

OBJECTIVE: To systematically synthesize evidence from a broad range of studies on the association between air pollution and migraine. BACKGROUND: Air pollution is a ubiquitous exposure that may trigger migraine attacks. There has been no systematic review of this possible association. METHODS: We searched for empirical studies assessing outdoor air pollution and any quantified migraine outcomes. We included short- and long-term studies with quantified air pollution exposures. We excluded studies of indoor air pollution, perfume, or tobacco smoke. We assessed the risk of bias with the World Health Organization's bias assessment instrument for air quality guidelines. RESULTS: The final review included 12 studies with over 4,000,000 participants. Designs included case-crossover, case-control, time series, and non-randomized pre-post intervention. Outcomes included migraine-related diagnoses, diary records, medical visits, and prescriptions. Rather than pooling the wide variety of exposures and outcomes into a meta-analysis, we tabulated the results. Point estimates above 1.00 reflected associations of increased risk. In single-pollutant models, the percent of point estimates above 1.00 were carbon monoxide 5/5 (100%), nitrogen dioxide 10/13 (78%), ozone 7/8 (88%), PM2.5 13/15 (87%), PM10 2/2 (100%), black carbon 0/1 (0%), methane 4/6 (75%), sulfur dioxide 3/5 (60%), industrial toxic waste 1/1 (100%), and proximity to oil and gas wells 6/13 (46%). In two-pollutant models, 16/17 (94%) of associations with nitrogen dioxide were above 1.00; however, more than 75% of the confidence intervals included the null value. Most studies had low to moderate risks of bias. Where differences were observed, stronger quality articles generally reported weaker associations. CONCLUSIONS: Balancing the generally strong methodologies with the small number of studies, point estimates were mainly above 1.00 for associations of carbon monoxide, nitrogen dioxide, ozone, and particulate matter with migraine. These results were most consistent for nitrogen dioxide.

Developing multivariable models for predicting headache improvement in patients with acute post-traumatic headache attributed to mild traumatic brain injury: A preliminary study.

OBJECTIVES/BACKGROUND: Post-traumatic headache (PTH) is a common symptom after mild traumatic brain injury (mTBI). Although there have been several studies that have used clinical features of PTH to attempt to predict headache recovery, currently no accurate methods exist for predicting individuals' improvement from acute PTH. This study investigated the utility of clinical questionnaires for predicting (i) headache improvement at 3 and 6 months, and (ii) headache trajectories over the first 3 months. METHODS: We conducted a clinic-based observational longitudinal study of patients with acute PTH who completed a battery of clinical questionnaires within 0-59 days post-mTBI. The battery included headache history, symptom evaluation, cognitive tests, psychological tests, and scales assessing photosensitivity, hyperacusis, insomnia, cutaneous allodynia, and substance use. Each participant completed a web-based headache diary, which was used to determine headache improvement. RESULTS: Thirty-seven participants with acute PTH (mean age = 42.7, standard deviation [SD] = 12.0; 25 females/12 males) completed questionnaires at an average of 21.7 (SD = 13.1) days post-mTBI. The classification of headache improvement or non-improvement at 3 and 6 months achieved cross-validation area under the curve (AUC) of 0.72 (95% confidence interval [CI] 0.55 to 0.89) and 0.84 (95% CI 0.66 to 1.00). Sub-models trained using only the top five features still achieved 0.72 (95% CI 0.55 to 0.90) and 0.77 (95% CI 0.52 to 1.00) AUC. The top five contributing features were from three questionnaires: Pain Catastrophizing Scale total score and helplessness sub-domain score; Sports Concussion Assessment Tool Symptom Evaluation total score and number of symptoms; and the State-Trait Anxiety Inventory score. The functional regression model achieved R = 0.64 for modeling headache trajectory over the first 3 months. CONCLUSION: Questionnaires completed following mTBI have good utility for predicting headache improvement at 3 and 6 months in the future as well as the evolving headache trajectory. Reducing the battery to only three questionnaires, which assess post-concussive symptom load and biopsychosocialecologic factors, was helpful to determine a reasonable prediction accuracy for headache improvement.

Treatment with the monoclonal calcitonin gene-related peptide receptor antibody erenumab: A real-life study.

BACKGROUND AND PURPOSE: New prophylactics for migraine, targeting calcitonin gene-related peptide (CGRP), have recently emerged. Real-world data are important for a comprehensive understanding of treatment response. We assessed the consistency of response to erenumab, a monoclonal CGRP receptor antibody, in a real-world setting, in order to determine which patients may be considered responders in clinical practice. METHODS: All erenumab-treated patients (n = 100) completed a time-locked daily electronic diary, and an automated algorithm was used to monitor treatment response. Monthly migraine days (MMD), non-migrainous headache days, days of acute medication use (MAMD), well-being and coping with pain were assessed for a 6-month period. The primary outcome was reduction in MMD compared to baseline. RESULTS: The numbers of MMD and MAMD decreased in all months, in both episodic and chronic migraine patients, compared to baseline (p < 0.001), while general well-being (p < 0.001) and coping with pain (p < 0.001) also improved. Of all patients, 36% had an MMD reduction of ≥50% in ≥3/6 months, and 6% had such a reduction in all 6 months. For a ≥30% MMD reduction, the figures were 60% and 24%, respectively. Almost 90% of patients with an average MMD reduction of ≥30% over the first 3 months had a sustained response in the last 3 months. In addition, 20% of patients without an initial response (average <30%), had a delayed response (average ≥30%) in the last 3 months. CONCLUSION: Erenumab was effective in migraine patients who were highly refractory to previous prophylactics. As a practical guideline, we propose that treatment be continued for at least 6 months and that patients with a ≥30% MMD reduction in at least half of the treatment period should be considered to be responders.

Effect of calcitonin gene-related peptide (-receptor) antibodies in chronic cluster headache: Results from a retrospective case series support individual treatment attempts.

OBJECTIVE: To assess the efficacy of monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor in chronic cluster headache (CCH) treatment under real world conditions. BACKGROUND: Calcitonin gene-related peptide has an important pathophysiological role in cluster headache. Although the randomised controlled trial with the calcitonin gene-related peptide antibody galcanezumab was negative, chronic cluster headache patients with insufficient response to other preventive treatments have been receiving individual off-label treatment attempts with calcitonin gene-related peptide-(receptor) antibodies. METHODS: Data from 22 chronic cluster headache patients who received at least one dose of a calcitonin gene-related peptide(-receptor) antibody and recorded attack frequency in a headache diary were retrospectively collected at eight headache centres. RESULTS: The number of previous preventive therapies was 6.5 ± 2.4 (mean ± standard deviation, range: 2-11). The average number of attacks per week was 23.3 ± 16.4 at baseline and significantly decreased by -9.2 ± 9.7 in the first month of treatment with a calcitonin gene-related peptide(-receptor) antibody (p < 0.001). Fifty-five percent of the patients were 50% responders and 36% were 75% responders with respect to attack frequency. Significant reduction of attack frequency started at week 1 (-6.8 ± 2.8 attacks, p < 0.01). Results were corroborated by significant decreases in weekly uses of acute headache medication (-9.8 ± 7.6, p < 0.001) and pain intensity during attacks (-1.2 ± 2.0, numerical rating scale (NRS) [0-10], p < 0.01) in the first month. In months 2 (n = 14) and 3 (n = 10), reduction of attack frequency from baseline was -8.0 ± 8.4 (p = 0.004) and -9.1 ± 10.0 (p = 0.024), respectively. CONCLUSION: Under real-world conditions, individual treatment with calcitonin gene-related peptide(-receptor) antibodies was effective in 55% of our chronic cluster headache patients. This finding supports individual off-label treatment attempts with calcitonin gene-related peptide-(receptor) antibodies in chronic cluster headache patients insufficiently responding to other therapies.

Aids to management of headache disorders in primary care (2nd edition) : on behalf of the European Headache Federation and Lifting The Burden: the Global Campaign against Headache.

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.

Follow-up over 20 months confirms gains of online behavioural training in frequent episodic migraine.

Aim This study examined the change over 20 months in 178 participants with frequent episodic migraine under adequate treatment as usual, who had completed online behavioural training (oBT) in migraine self-management either directly (group 1, n = 120) or after 10 months of watchful waiting (group 2, n = 58). Methods Participants completed questionnaires and an online headache diary and migraine monitor following the International Classification of Headache Disorders at T0 (baseline), T1 (post-training), T2 (6-month follow-up; extended baseline in group 2), T3 (post-training, group 2 only) and T4 (group 1: 16-month follow-up; group 2: 6-month follow-up). Statistical analyses were conducted on the observed data without imputation of missing observations. Results Both groups were highly comparable. The data over time revealed benefits in response to oBT, with significant between-group differences in the change achieved in the training episodes T2-T0 (group 1) and T4-T2 (group 2). Improved attack frequency ( M = -23%) was higher in participants with more (i.e. 4-6) attacks per month at baseline, and the effects of oBT were durable over 16 months of follow-up. Conclusions oBT is beneficial in frequent episodic migraine, which deserves special efforts in care. Self-management variants such as oBT reach patients easily and supplement these efforts with durable results.

Menstrual versus non-menstrual attacks of migraine without aura in women with and without menstrual migraine.

OBJECTIVE: The objective of this article is to compare clinical characteristics of menstrual and non-menstrual attacks of migraine without aura (MO), prospectively recorded in a headache diary, by women with and without a diagnosis of menstrual migraine without aura (MM) according to the International Classification of Headache Disorders (ICHD). MATERIAL AND METHODS: A total of 237 women from the general population with self-reported migraine in ≥50% of their menstrual periods were interviewed and classified by a physician according to the criteria of the ICHD II. Subsequently, all participants were instructed to complete a prospective headache diary for at least three menstrual cycles. Clinical characteristics of menstrual and non-menstrual attacks of MO were compared by a regression model for repeated measurements. RESULTS: In total, 123 (52%) women completed the diary. In the 56 women who were prospectively diagnosed with MM by diary, the menstrual MO-attacks were longer (on average 10.65 hours, 99% CI 3.17-18.12) and more frequently accompanied by severe nausea (OR 2.14, 99% CI 1.20-3.84) than non-menstrual MO-attacks. No significant differences between menstrual and non-menstrual MO-attacks were found among women with MO, but no MM. CONCLUSION: In women from the general population, menstrual MO-attacks differ from non-menstrual attacks only in women who fulfil the ICHD criteria for MM.

A clinical interview versus prospective headache diaries in the diagnosis of menstrual migraine without aura.

OBJECTIVES: The objective of this article is to compare the diagnosis of menstrual migraine without aura (MM) from a clinical interview with prospective headache diaries in a population-based study. MATERIAL AND METHODS: A total of 237 women with self-reported migraine in at least half of menstruations were interviewed by a neurologist about headache and diagnosed according to the International Classification of Headache Disorders II (ICHD II). Additionally, the MM criteria were expanded to include other types of migraine related to menstruation. Subsequently, all women were asked to complete three month prospective headache diaries. RESULTS: A total of 123 (52%) women completed both clinical interview and diaries. Thirty-eight women were excluded from the analyses: Two had incomplete diaries and 36 women recorded ≤1 menstruation, leaving 85 diaries eligible for analysis. Sensitivity, specificity, positive and negative predictive value and Kappa for the diagnosis of MM in clinical interview vs. headache diary were 82%, 83%, 90%, 71% and 0.62 (95% CI 0.45-0.79). Using a broader definition of MM, Kappa was 0.64 (95% CI 0.47-0.83). CONCLUSION: A thorough clinical interview is valid for the diagnosis of MM. When this is undertaken, prospective headache diaries should not be mandatory to diagnose MM but may be necessary to exclude a chance association.

Medium-term effectiveness of online behavioral training in migraine self-management: A randomized trial controlled over 10 months.

AIM: This randomized, controlled trial examined the medium-term effectiveness of online behavioral training in migraine self-management (oBT; N = 195) versus waitlist control (WLC; N = 173) on attack frequency, indicators of self-management (primary outcomes), headache top intensity, use of rescue medications, quality of life and disability (secondary outcomes). METHODS: An online headache diary following the ICHD-II and questionnaires were completed at baseline (T0), post-training (T1) and six months later (T2). Missing data (T1: 24%; T2: 37%) were handled by multiple imputation. We established effect sizes (ES) and tested between-group differences over time with linear mixed modelling techniques based on the intention-to-treat principle. RESULTS: At T2, attack frequency had improved significantly in oBT (-23%, ES = 0.66) but also in WLC (-19%; ES = 0.52). Self-efficacy, internal and external control in migraine management--and triptan use--improved only in oBT, however. This indicates different processes in both groups and could signify (the start of) active self-management in oBT. Also, only oBT improved migraine-specific quality of life to a sizable extent. CONCLUSIONS: oBT produced self-management gains but could not account for improved attack frequency, because WLC improved as well. The perspective that BT effects develop gradually, and that online delivery will boost BT outreach, justifies further research.

Headache providers' perspectives of headache diaries in the era of increasing technology use: a qualitative study.

Background: No matter what type of headache is being considered across various populations, one of the mainstays of headache medicine is headache tracking. This self-management tool enables patients and their providers to understand patients' underlying symptoms and the effects of treatments they have tried. This is important to determining whether headaches are related to menses for women's health, to determining the time of headache occurrence, e.g., hypnic headache, and the location and duration of symptoms, e.g., trigeminal autonomic cephalgia. Prior research has investigated what people with headaches perceive about headache diary use and how people with headaches utilize electronic headache diaries. However, headache providers' perspectives on the important factors related to headache diaries are less known. Previously, using the Modified Delphi Process, a panel of four experts opined what they perceived as the most important factors for a headache diary. We sought to better understand headache providers' perspectives about headache diary/app usage from providers working in various institutions nationwide. Methods: We conducted 20 semi-structured qualitative interviews of headache providers across the US from various institutions and asked them their perspectives on headache diary use. We transcribed the interviews, which two independent coders then coded. Themes and subthemes were developed using grounded theory qualitative analysis. Results: Six themes emerged: (1) Providers were generally agnostic regarding the headache tracking method, but nearly all recommend the use of smartphones for tracking; (2) Providers had concerns regarding the accessibility of headache trackers; (3) Providers noted benefits to integrating headache tracking data into the EMR but had mixed opinions on how this integration might be done; (4) Providers had mixed opinions regarding the utility and interpretation of the data, specifically regarding data accuracy and efficiency; (5) Providers generally felt that headache tracking lends itself to more collaborative plan management; (6) Providers recommend behavioral health apps for patients but stated that there are few digital behavioral health interventions for headache specifically. Conclusion: Interviews of headache providers, recommenders, and users of headache data are vital informants who can provide a robust amount of information about headache diary development, use in different populations, integration, and more.

Digital diary App use for migraine in primary care: Prospective cohort study.

BACKGROUND: Headache diaries are recommended for migraine management in primary care. OBJECTIVE: Determine the acceptability and use of a digital headache diary App for migraine METHODS: Evaluative prospective primary care cohort study in North of England. Part 1 was a postal survey; if responders were interested, in Part 2 participants trialled the digital N1-Headache App headache diary for 90 days, followed by survey feedback on the App's usability. RESULTS: A total of 637 out of 2189 invited patients (29%) completed the initial survey, and 32% of respondents had previously used a headache diary; 437 out of 637 patients (69%) were interested in using the App. Regression analysis showed that interested patients were those with more severe migraines that limit physical/intellectual activities, and who indicate to not know enough about their migraine. Actual registration numbers and compliance with the App was very modest; 53 out of 173 participants (23%), who ultimately activated their personal N1-Headache App account, were able to generate a personalised trigger and protector map & report. Furthermore, at the end of the 90 day App trial period there was a non-significant trend towards improvements in participants' health confidence levels. CONCLUSION: Migraine patients - particularly those with more severe and frequent migraines - show an interest in using a digital headache diary App, Ultimately, consistent daily use is very modest. The challenge is to improve App usage and compliance rates to allow interpretation of more patients' migraine trigger and/or protector patterns, and wider use amongst patients.

Effects of Botulinum Toxin on Migraine Attack Features in Chronic Migraine: A Six-Month Open-Label Observation Study through Electronic Diary Smartphone Application.

OnobotulintoxinA (OBT-A) is a treatment option for Chronic Migraine (CM). It works on central sensitization and pain but its mode of action is still unknown. To observe how OBT-A treatment works on single migraine attacks, this paper covers an over-6-month observation period through self-reported smartphone application data. This was an observational, open-label cohort study conducted on 34 CM patients under OBT-A treatment, selected between December 2016 and December 2017, who agreed to download a smartphone headache diary application (Aid Diary) according to the study instructions. The analysis was conducted using the smartphone application data reports on allodynia, intensity and extension of pain, and vegetative symptoms. We analysed a total of 707 records of single migraine attacks reported by compliant users (n = 34) in real-time. OBT-A significantly reduced allodynia, the number of vegetative symptoms, pain extension and intensity in single migraine attacks. Pain intensity was correlated with pain extension. In single migraine attacks, OBT-A improved symptoms of central sensitization. This action could be exerted by modulating nociceptive transmission and reducing the burden of single migraine episodes and improving the overall quality of life.

The association between abdominal obesity and characteristics of migraine attacks in Iranian adults.

BACKGROUND: Migraine is a primary headache disorder that affects the neurovascular system. Recent studies have shown that migraine patients with general obesity have higher characteristics of migraine attacks compared with normal weight patients, but data on central obesity are scarce. This study was done to assess the relationship between central obesity and the characteristics of migraine attacks in migraine patients. MATERIALS AND METHODS: This cross-sectional study was conducted on 129 migraine patients (28 men and 101 women), aged 15-67 years, in Isfahan, Iran. Anthropometric measurements such as waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR) and waist-height ratio (WHtR), as well as characteristics of migraine attacks such as severity, frequency, duration, and headache diary result (HDR) was determined for each participant. Linear regression was used to examine the association between anthropometric measurements and characteristics of migraine attacks. P value less than 0.05 was considered significant. RESULTS: WC, WHR, and WHtR were positively associated with the severity (P-value: WC: 0.002, WHR: 0.002, WHtR: 0.001) and frequency (P-value: WC: 0.006, WHR: 0.01, WHtR: 0.002) of migraine attacks. Moreover, we found a significant association between WC (P = 0.001), WHR (P = 0.004), and WHtR (P < 0.001) with HDR. No significant relationship was observed between central obesity indicators and duration of migraine attacks. CONCLUSIONS: Central obesity indicators were positively associated with the severity and frequency of migraine attacks as well as HDR, but not with duration of attacks. Based on our findings, it can be concluded that weight loss may decrease the characteristics of migraine attacks.