Establishing the relationship between antecedent events and headaches is a formidable challenge. Successfully addressing this challenge should provide insights into disease mechanisms and lead to new strategies for treatment. In the second paper in this series, we review the available literature on trigger factors and premonitory features.

We conclude that trigger factors and premonitory symptoms are very common, but that the frequency estimates vary widely based on the study approach and population. We recommend that multimodal approaches are necessary for the comprehensive study of predictive biophenotypes as determined by triggers and premonitory symptoms, including retrospective and prospective cohort studies and case-crossover studies.

Migraine shares a complex and poorly understood relationship with sleep. Patients consistently report poor sleep prior to migraine attacks and during them, identifying poor sleep as a migraine trigger. However, anecdotally, sleep is reported to serve a therapeutic role in terminating headache. Are the associations between migraine and sleep simply the result of various bidirectional relationships? A growing body of evidence suggests there may be a common underlying etiology as well. Our objective was to review studies of sleep and migraine from the last 2 decades utilizing validated subjective and objective measures of sleep and to explore potential mechanisms underlying this complex relationship by incorporating recent advances in neuroscience. We specifically focus on insomnia, obstructive sleep apnea, parasomnias, sleep related movement disorders, and REM sleep related disorders and their relationship to migraine. Parts of brainstem-cortical networks involved in sleep physiology are unintentionally being identified as important factors in the common migraine pathway. Recent discoveries on anatomic localization (the hypothalamus as a key and early mediator in the pathophysiology of migraine), common mediating signaling molecules (such as serotonin and dopamine), and the discovery of a new CNS waste removal system, the glymphatic system, all point to a common pathophysiology manifesting in migraine and sleep problems.

Objective To evaluate relationships among modifiable psychological factors and chronic migraine and severe migraine-related disability in a clinic-based sample of persons with migraine. Background Evidence evaluating relationships between modifiable psychological factors and chronic migraine and severe migraine-related disability is lacking in people with migraine presenting for routine clinical care. Methods Adults with migraine completed surveys during routinely scheduled visits to a tertiary headache center. Participants completed surveys assessing chronic migraine (meeting criteria for migraine with ≥15 headache days in the past month), severe migraine disability (Migraine Disability Assessment Scale score ≥ 21), and modifiable psychological factors [depressive symptoms (Patient Health Questionnaire-9), anxious symptoms (Generalized Anxiety Disorder-7), Pain Catastrophizing Scale and Headache Specific Locus of Control]. Logistic regression evaluated relationships between modifiable psychological factors and chronic migraine and severe migraine disability. Results Among 90 eligible participants the mean age was 45.0 (SD = 12.4); 84.8% were women. One-third (36.0%) met study criteria for chronic migraine; half of participants (51.5%) reported severe migraine-related disability. Higher depressive symptoms (OR = 1.99, 95% CI = 1,11, 3.55) and chance HSLC (OR = 1.85, 95% CI = 1.13, 1.43) were associated with chronic migraine. Higher depressive symptoms (OR = 3.54, 95%CI = 1.49, 8.41), anxiety symptoms (OR = 3.65, 95% CI = 1.65, 8.06), and pain catastrophizing (OR = 1.95, 95% CI = 1.14, 3.35), were associated with severe migraine-related disability. Conclusions Psychiatric symptoms and pain catastrophizing were strongly associated with severe migraine-related disability. Depression and chance locus of control were associated with chronic migraine. This study supports the need for longitudinal observational studies to evaluate relationships among naturalistic variation in psychological factors, migraine-related disability and migraine chronification.

Objective To test whether behavioral weight loss (BWL) intervention decreases headaches in women with comorbid migraine and overweight/obesity. Methods This randomized, single-blind trial allocated women [18–50 years old, 4–20 migraine days/month, Body Mass Index (BMI)=25.0–49.9 kg/m2] to 16 weeks of BWL, (n=54) that targeted exercise and eating behaviors for weight loss, or Migraine Education control (ME, n=56) that delivered didactic instruction on migraine and treatments. Participants completed a 4-week smartphone headache diary at baseline, post-treatment (16–20 weeks) and follow-up (32–36 weeks). The primary outcome was post-treatment change in migraine days/month, analyzed via linear mixed effects models. Results Of 110 participants randomized, 85 (78%) and 80 (73%) completed post-treatment and follow-up. Although BWL achieved greater weight loss [mean (95% CI) kg] vs. ME at post-treatment [−3.8 (−2.5, −5.0) vs. +0.9 (−0.4,2.2) p<.001] and follow-up [−3.2 (−2.0, −4.5) vs. +1.1 (−0.2,2.4), p<.001], there were no significant group (BWL vs. ME) differences [mean (95%CI)] migraine days/month at post-treatment [−3.0 (−2.0, −4.0) vs. −4.0 (−2.9, −5.0), p=.185] or follow-up [−3.8 (−2.7, −4.8) vs. −4.4 (−3.4, −5.5), p=.378]. Conclusion Contrary to hypotheses, BWL and ME yielded similar, sustained reductions in migraine headaches. Future research should evaluate whether adding BWL to standard pharmacologic and/or non-pharmacologic migraine treatment approaches yields greater benefits.

Migraine is a common neurological disorder with significantly higher incidence and prevalence in women than men. The presentation of the disease in women is modulated by changes in sex hormones from adolescence to pregnancy and menopause. Yet, the effect of sex influences has often been neglected in both basic and clinical and in clinical management of the disease. In this review, evidence from epidemiological, clinical, animal, and neuroimaging studies on the significance of the sex-related influences in migraine is presented, and the unmet needs in each area are discussed. © 2016 Wiley Periodicals, Inc.

Objective/Background Obesity is related to migraine. Maladaptive pain coping strategies (e.g., pain catastrophizing), may provide insight into this relationship. In women with migraine and obesity, we cross-sectionally assessed: 1) prevalence of clinical catastrophizing; 2) characteristics of those with and without clinical catastrophizing; and 3) associations of catastrophizing with headache features. Methods Obese women migraineurs seeking weight loss treatment (n=105) recorded daily migraine activity for 1-month via smartphone and completed the Pain Catastrophizing Scale (PCS). Clinical catastrophizing was defined as total PCS score ≥30. The Headache Impact Test (HIT-6), Allodynia Symptom Checklist (ASC-12), Headache Management Self-Efficacy Scale (HMSE), and assessments for depression (CES-D) and anxiety (GAD-7) were also administered. Using PCS scores and Body Mass Index (BMI) as predictors in linear regression, we modeled a series of headache features (i.e., headache days, HIT-6, etc.) as outcomes. Results One-quarter (25.7%;95%CI=17.2%–34.1%) of participants met criteria for clinical catastrophizing: they had higher BMI(37.9±7.5 vs. 34.4±5.7 kg/m2, p=0.035), longer migraine attack duration(160.8±145.0 vs. 97.5±75.2 hours/month, p=0.038), higher HIT-6 scores(68.7±4.6 vs. 64.5±3.9, p<0.001), more allodynia(7.0±4.1 vs. 4.5±3.5, p<0.003), depression(25.4±12.4 vs. 13.3±9.2, p<0.001), and anxiety(11.0±5.2 vs. 5.6±4.1, p<0.001), and lower self-efficacy(80.1±25.6 vs. 104.7±18.9, p<0.001) compared to participants without clinical catastrophizing. The odds of chronic migraine were nearly 4-fold greater in those with (n=8/29.6%) versus without (n=8/10.3%) clinical catastrophizing (OR=3.68;95%CI=1.22–11.10, p=0.021). In all participants, higher PCS scores were related to more migraine days(β=0.331, p=0.001), longer attack duration(β=0.390, p<0.001), higher HIT-6 scores(β=0.425, p<0.001), and lower HMSE scores (β=−0.437, p<0.001). Higher BMI, but not higher PCS scores, was related to more frequent attacks (β=−0.203, p=0.044). Conclusions One-quarter of participants with migraine and obesity reported clinical catastrophizing. These individuals had more frequent attacks/chronicity, longer attack duration, higher pain sensitivity, greater headache impact, and lower headache management self-efficacy. In all participants, PCS scores were related to several migraine characteristics, above and beyond the effects of obesity. Prospective studies are needed to determine sequence and mechanisms of relationships between catastrophizing, obesity, and migraine.

BackgroundMigraine, particularly chronic migraine (CM), is underdiagnosed and undertreated worldwide. Our objective was to develop and validate a self-administered tool (ID-CM) to identify migraine and CM.MethodsID-CM was developed in four stages. (1) Expert clinicians suggested candidate items from existing instruments and experience (Delphi Panel method). (2) Candidate items were reviewed by people with CM during cognitive debriefing interviews. (3) Items were administered to a Web panel of people with severe headache to assess psychometric properties and refine ID-CM. (4) Classification accuracy was assessed using an ICHD-3β gold-standard clinician diagnosis.ResultsStages 1 and 2 identified 20 items selected for psychometric validation in stage 3 (n = 1562). The 12 psychometrically robust items from stage 3 underwent validity testing in stage 4. A scoring algorithm applied to four symptom items (moderate/severe pain intensity, photophobia, phonophobia, nausea) accurately classified most migraine cases among 111 people (sensitivity = 83.5%, specificity = 88.5%). Augmenting this algorithm with eight items assessing headache frequency, disability, medication use, and planning disruption correctly classified most CM cases (sensitivity = 80.6%, specificity = 88.6%).DiscussionID-CM is a simple yet accurate tool that correctly classifies most individuals with migraine and CM. Further testing in other settings will also be valuable.