Evaluating patient and family preferences for acute and preventive pediatric headache treatment.

OBJECTIVE: To describe acute and preventive treatment preferences among youth with migraine and their parents/guardians, and to describe the degree of youth-parent/guardian preference agreement. BACKGROUND: Headache disorders are common in youth, but little is known about patient and family preferences for headache treatments and outcomes. METHODS: In this cross-sectional survey, a headache treatment preferences questionnaire was co-created with stakeholders, piloted, and distributed to consenting youth with migraine aged 9-18 years and parents/guardians at a tertiary care headache clinic in western Canada. Response data were summarized for youth and parents/guardians separately, and agreement rates within a youth-parent/guardian pair were compared to a hypothesized agreement rate of 80% for the primary questionnaire items. RESULTS: Seventy-two youth and n = 94 parents/guardians participated, with n = 63 in youth-parent/guardian pairs. Freedom from pain and rapid relief, and reducing pain severity and headache frequency were top acute and preventive treatment priorities, respectively. More than 90% (69/72) agreed that ≥ 50% reduction in headache frequency was a good target. For both acute and preventive interventions, swallowed pill-based options were most often selected as the preferred first-line treatment, with neuromodulation selected as the preferred second-line treatment. The level of agreement within youth-parent/guardian pairs on preferred treatment modalities was lower than hypothesized for acute (63% [40/63], 95% confidence interval [CI] = 52-75%, χ2 = 10.73, p = 0.001) but not for preventive treatment (73% [46/63], 95% CI = 62-84%, χ2 = 1.92, p = 0.166). Regarding which treatment modalities were perceived as most effective, youth-parent agreement was lower than hypothesized for both acute (48% [30/63], 95% CI = 35-60%, χ2 = 41.29, p < 0.001) and preventive treatment (46% [29/63], 95% CI = 34-58%, χ2 = 45.43, p < 0.001). CONCLUSION: Youth and family preferences aligned qualitatively, but sometimes diverged quantitatively, from typical clinical trial outcomes. The level of agreement within youth-parent/guardian pairs on treatment preferences and perceptions was low. Clinicians should consider both perspectives as they may be divergent.

Clinical factors associated with day-to-day peak pain severity in individuals with chronic migraine: A cohort study using daily prospective diary data.

OBJECTIVE: To describe the association between day-to-day peak pain severity and clinical factors in individuals with chronic migraine (CM). BACKGROUND: Little is known about how clinical factors relate to day-to-day pain severity in individuals with CM. METHODS: Adults with CM were enrolled into this observational prospective cohort study that collected daily data about headache, associated symptoms, and lifestyle factors using a digital health platform (N1-Headache™) for 90 days. "Migraine days" were defined as days in which a headache occurred that had features described by the International Classification of Headache Disorders criteria. On these days, peak pain severity was recorded on a 4-point scale; on non-headache days peak pain severity was imputed as "0/none". The associations between peak pain severity and 12 clinical factors were modeled and adjusted for sex, age, daily headache, presence of menstrual bleeding, day of the week, and disability. All numerical and Likert scale variables were standardized prior to analysis. RESULTS: Data were available for 392 participants (35,280 tracked days). The sample was predominantly female (90.6%), with a mean (standard deviation) age of 39.9 (12.8) years. In the final multivariable model with random intercept and slopes, higher than typical self-reported levels of standardized stress (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.04-1.11), standardized irritability (OR 1.05, 95% CI 1.02-1.08), standardized sadness (OR 1.05, 95% CI 1.02-1.07), fatigue (OR 1.25, 95% CI 1.15-1.36), eyestrain (OR 1.38, 95% CI 1.26-1.52), neck pain (OR 1.94, 95% CI 1.76-2.13), skin sensitivity (OR 1.61, 95% CI 1.44-1.80), and dehydration (OR 1.29, 95% CI 1.18-1.42) were associated with higher reported peak pain severity levels, while standardized sleep quality (OR 0.96, 95% CI 0.93-0.99) and standardized waking feeling refreshed (OR 0.84, 95% CI 0.81-0.88) were associated with lower reported peak pain severity levels. The inclusion of a random intercept and random slopes improved upon more parsimonious models and illustrated large differences in individuals' reporting of peak severity according to the levels of the associated clinical factors. CONCLUSION: Our data showed that the experience of CM, from a pain severity perspective, is complex, related to multiple clinical variables, and highly individualized. These results suggest that future work should aim to study a personalized approach to both medical and behavioral interventions for CM based on which clinical factors relate to the individual's experience of pain severity.

Anxiety and depressive symptoms and migraine-related outcomes in children and adolescents.

OBJECTIVE: The objective of this study was to explore the longitudinal relationship between anxiety and depressive symptoms and migraine outcomes in children and adolescents. BACKGROUND: Children and adolescents with migraine experience more anxiety and depressive symptoms than their peers without migraine, but it is unknown if these symptoms are associated with differential migraine outcomes. METHODS: In this prospective clinical cohort study, children and adolescents aged 8.0-18.0 years with migraine completed headache questionnaires and validated measures of anxiety and depressive symptoms (Patient-Reported Outcomes Measurement Information System) at an initial consultation and at their first follow-up visit with a neurologist. Changes in monthly headache frequency and changes in migraine-related disability (Pediatric Migraine Disability Assessment) were tracked at each time point. The relationships between these migraine outcomes and anxiety and depressive symptoms were estimated using models controlling for sex, age, headache frequency, and treatment type. RESULTS: There were 123 consenting participants. In models adjusted for age, sex, baseline disability score, and treatment type, baseline anxiety and depressive symptom levels were not significantly associated with change in headache frequency (for anxiety symptoms: ß = -0.05, 95% confidence interval [CI] = -0.268 to 0.166, p = 0.639; for depressive symptoms: ß = 0.14, 95% CI = -0.079 to 0.359, p = 0.209). Similarly, in models adjusted for age, sex, baseline headache frequency, and treatment type, the change in disability was not associated with baseline anxiety (ß = -0.45, 95% CI = -1.69 to 0.78, p = 0.470), nor with baseline depressive symptom scores (ß = 0.16, 95% CI = -1.07 to 1.40, p = 0.796). In post hoc exploratory analyses (N = 84 with anxiety and N = 82 with depressive symptom data at both visits), there were also no significant associations between change in mental health symptoms and change in headache frequency (for anxiety symptoms: ß = -0.084, 95% CI = -0.246 to 0.078, p = 0.306; for depressive symptoms: ß = -0.013, 95% CI = -0.164 to 0.138, p = 0.865). Similarly, the change in disability scores between visits was not related to the change in anxiety (ß = 0.85, 95% CI = -0.095 to 1.78, p = 0.077) nor depressive symptom scores (ß = 0.32, 95% CI = -0.51 to 1.15, p = 0.446). CONCLUSION: Baseline anxiety and depressive symptom levels were not associated with longitudinal migraine outcomes and neither were longitudinal changes in anxiety and depressive symptom levels; this contradicts popular clinical belief that mental health symptoms predict or consistently change in tandem with migraine outcomes.

The 2023 protocol for update to acute treatment of adults with migraine in the emergency department: The American Headache Society evidence assessment of parenteral pharmacotherapies.

OBJECTIVES: The primary objective of this proposed guideline is to update the prior 2016 guideline on parenteral pharmacotherapies for the management of adults with a migraine attack in the emergency department (ED). METHODS: We will conduct an updated systematic review and meta-analysis using the 2016 guideline methodology to provide clinical recommendations. The same search strategy will be used for studies up to 2023, with a new search strategy added to capture studies of nerve blocks and sphenopalatine blocks. Medline, Embase, Cochrane, clinicaltrials.gov, and the World Health Organization International Clinical Trial Registry Platform will be searched. Our inclusion criteria consist of studies involving adults with a diagnosis of migraine, utilizing medications administered intravenously, intramuscularly, or subcutaneously in a randomized controlled trial design. Two authors will perform the selection of studies based on title and abstract, followed by a full-text review. A third author will intervene in cases of disagreements. Data will be recorded in a standardized worksheet and subjected to verification. The risk of bias will be assessed using the American Academy of Neurology tool. When applicable, a meta-analysis will be conducted. The efficacy of medications will be evaluated, categorizing them as "highly likely," "likely", or "possibly effective" or "ineffective." Subsequently, clinical recommendations will be developed, considering the risk associated with the medications, following the American Academy of Neurology recommendation development process. RESULTS: The goal of this updated guideline will be to provide guidance on which injectable medications, including interventional approaches (i.e., nerve blocks, sphenopalatine ganglion), should be considered effective acute treatment for adults with migraine who present to an ED. CONCLUSIONS: The methods outlined in this protocol will be used in the design of a future systematic review and meta-analysis-informed guideline, which will then be assessed by and submitted for endorsement by the American Headache Society.

Longitudinal trajectories of posttraumatic headache after pediatric mild traumatic brain injury.

OBJECTIVE: This prospective, longitudinal cohort study examined the trajectory, classification, and features of posttraumatic headache after pediatric mild traumatic brain injury. METHODS: Children (N = 213; ages 8.00 to 16.99 years) were recruited from two pediatric emergency departments <24 hours of sustaining a mild traumatic brain injury or mild orthopedic injury. At 10 days, three months, and six months postinjury, parents completed a standardized questionnaire that was used to classify premorbid and posttraumatic headache as migraine, tension-type headache, or not otherwise classified. Multilevel mixed effects models were used to examine posttraumatic headache rate, severity, frequency, and duration in relation to group, time postinjury, and premorbid headache, controlling for age, sex, and site. RESULTS: PTH risk was greater after mild traumatic brain injury than mild orthopedic injury at 10 days (odds ratio = 197.41, p < .001) and three months postinjury (odds ratio = 3.50, p = .030), especially in children without premorbid headache. Posttraumatic headache was more frequent after mild traumatic brain injury than mild orthopedic injury, ß (95% confidence interval) = 0.80 (0.05, 1.55). Groups did not differ in other examined headache features and classification any time postinjury. CONCLUSIONS: Posttraumatic headache risk increases after mild traumatic brain injury relative to mild orthopedic injury for approximately three months postinjury, but is not clearly associated with a distinct phenotype.

Impact of monthly headache days on migraine-related quality of life: Results from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study.

OBJECTIVE: To characterize the direct impact of monthly headache days (MHDs) on health-related quality of life (HRQoL) in people with migraine and the potential mediating effects of anxiety, depression, and allodynia. BACKGROUND: Although the general relationship between increased migraine frequency (i.e., MHDs) and reduced HRQoL is well established, the degree to which reduced HRQoL is due to a direct effect of increased MHDs or attributable to mediating factors remains uncertain. METHODS: Cross-sectional baseline data from participants with migraine who completed the Core and Comorbidities/Endophenotypes modules in the 2012-2013 US Chronic Migraine Epidemiology and Outcomes (CaMEO) study, a longitudinal web-based survey study, were analyzed. The potential contribution of depression, anxiety, and/or allodynia to the observed effects of MHDs on HRQoL as measured by the Migraine-Specific Quality-of-Life Questionnaire version 2.1 (MSQ) was evaluated. RESULTS: A total of 12,715 respondents were included in the analyses. The MSQ domain scores demonstrated progressive declines with increasing MHD categories (B = -1.23 to -0.60; p < 0.001). The observed HRQoL decrements associated with increasing MHDs were partially mediated by the presence of depression, anxiety, and allodynia. The MHD values predicted 24.0%-32.4% of the observed variation in the MSQ domains. Depression mediated 15.2%-24.3%, allodynia mediated 9.6%-16.1%, and anxiety mediated 2.3%-6.0% of the observed MHD effects on the MSQ. CONCLUSIONS: Increased MHD values were associated with lower MSQ scores; the impact of MHDs on the MSQ domain scores was partially mediated by the presence of depression, anxiety, and allodynia. MHDs remain the predominant driver of the MSQ variation; moreover, most of the variation in the MSQ remains unexplained by the variables we analyzed. Future longitudinal analyses and studies may help clarify the contribution of MHDs, comorbidities, and other factors to changes in HRQoL.

Managing and Preventing Migraine in the Emergency Department: A Review.

Migraine is a leading cause of disability worldwide, and acute migraine attacks are a common reason for patients to seek care in the emergency department (ED). There have been recent advancements in the care of patients with migraine, specifically emerging evidence for nerve blocks and new pharmacological classes of medications like gepants and ditans. This article serves as a comprehensive review of migraine in the ED, including diagnosis and management of acute complications of migraine (eg, status migrainosus, migrainous infarct, persistent aura without infarction, and aura-triggered seizure) and use of evidence-based migraine-specific treatments in the ED. It highlights the role of migraine preventive medications and provides a framework for emergency physicians to prescribe them to eligible patients. Finally, it evaluates the evidence for nerve blocks in the treatment of migraine and introduces the possible role of gepants and ditans in the care of patients with migraine in the ED.

Engaging youth and parents in clinical pediatric research: A case-based example.

Background: Youth and parent engagement is a key component of clinical research. There are many ways to actively and meaningfully engage youth and parents as integral members of research teams, for example, through ad-hoc committees, advisory councils, or as co-leads on projects. When youth and parents are actively and meaningfully engaged in research projects, they share knowledge from their lived experiences to improve the quality and relevance of research. Methods: We describe a case-based example of engaging youth and parent research partners when co-designing a questionnaire to assess preferences for pediatric headache treatments, from both a researcher and youth/parent perspective. We also summarize best practices in patient and family engagement from the literature and pertinent guidelines to assist researchers with integrating patient and family engagement into their studies. Results: As researchers, we felt that the integration of a youth and parent engagement plan into our study significantly altered and strengthened questionnaire content validity. We encountered challenges throughout the process and detailed these experiences to help educate others about challenge mitigation and best practices in youth and parent engagement. As youth and parent partners, we felt that engaging in the process of questionnaire development was an exciting and empowering opportunity, and that our feedback was valued and integrated. Conclusions: By sharing our experience, we hope to catalyze thought and discussion around the importance of youth and parent engagement in pediatric research, with the goal of stimulating more appropriate, relevant, and high-quality pediatric research and clinical care in the future.

The spectrum of indomethacin-responsive headaches in children and adolescents.

BACKGROUND: Headaches with marked, specific response to indomethacin occur in children, but the phenotypic spectrum of this phenomenon has not been well-studied. METHODS: We reviewed pediatric patients with headache showing ≥80% improvement with indomethacin, from seven academic medical centers. RESULTS: We included 32 pediatric patients (16 females). Mean headache onset age was 10.9 y (range 2-16 y). Headache syndromes included hemicrania continua (n = 13), paroxysmal hemicrania (n = 10), primary stabbing headache (n = 2), short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (n = 1), primary exercise headache (n = 1) and primary cough headache (n = 1). Adverse events were reported in 13, most commonly gastrointestinal symptoms, which often improved with co-administration of gastro-protective agents. CONCLUSION: Indomethacin-responsive headaches occur in children and adolescents, and include headache syndromes, such as primary cough headache, previously thought to present only in adulthood. The incidence of adverse events is high, and patients must be co-treated with a gastroprotective agent.

Adverse childhood experiences and onset of migraine in Canadian adolescents: A cohort study.

BACKGROUND: Adverse childhood experiences (ACEs) are cross-sectionally associated with headache, including migraine, in pediatric populations. OBJECTIVE: The objective of this study was to determine whether ACEs are prospectively associated with incident health-professional diagnosed migraine and prevalence of non-migraine frequent headache in adolescence, either directly or indirectly through symptoms of depression and anxiety. METHODS: We used data from the National Longitudinal Survey of Children and Youth, a Canadian cohort study that followed children aged 0/1 at baseline, and the person most knowledgeable about them (PMK) until the child reached adolescence. The PMK reported on 14 ACEs (e.g., parental death) when the child was 4/5 and 6/7 years, and symptoms of depression and anxiety in late childhood (age 8/9 years), using a validated tool. Migraine (primary outcome) was ascertained via PMK report of a health-professional diagnosis, and non-migraine frequent headache (>1 time per week) was adolescent self-report, both measured at age 14/15. We estimated direct and indirect effects (IEs) on the log-odds scale through symptoms of depression and anxiety (mediator). We adjusted for sex, parental migraine, and economic deprivation. The analytic sample sizes were: n = 2058 (migraine) and n = 1730 (frequent headache). RESULTS: There were nunweighted  = 71 respondents with migraine (3.4%, 71/2058) and nunweighted  = 204 with non-migraine frequent headache (11.8%, 204/1730). Most respondents experienced no ACEs (weighted percentage = 55.7), followed by 1 ACE (weighted percentage = 34.7) and greater than or equal to two ACEs (weighted percentage = 9.6), respectively. There were direct associations between experiencing one (odds ratio [OR] = 1.71, 95% confidence interval [CI]: 1.01-2.87) and equal to or greater than two (OR = 2.33, 95% CI: 1.13-4.80) ACEs and migraine, but not for non-migraine frequent headache. There were no indirect relationships through symptoms of depression and anxiety for migraine (1 ACE: OR = 1.06, 95% CI: 0.99-1.13 and ≥2 ACEs: OR = 1.11, 95% CI: 0.98-1.28) or non-migraine frequent headache (1 ACE: OR = 0.99, 95% CI: 0.95-1.03 and ≥2 ACEs: OR = 0.98, 95% CI: 0.90-1.07). CONCLUSIONS: ACEs may confer an increased risk of migraine onset in adolescence. The association was not explained by symptoms of depression and anxiety in late childhood.

Outpatient Approach to Resistant and Refractory Migraine in Children and Adolescents: a Narrative Review.

PURPOSE OF REVIEW: Migraine is one of the top reasons for consulting a pediatric neurologist. Although the majority of children and adolescents who receive evidence-based first-line interventions for migraine will improve substantially, a subset of patients develop resistant or refractory migraine. RECENT FINDINGS: In this review, we summarize the level of evidence for a variety of acute and preventive treatment options to consider in children and adolescents with resistant or refractory migraine. We describe the level of evidence for interventional procedures (onabotulinumtoxinA injections, greater occipital and other nerve blocks), neuromodulation (single-pulse transcranial magnetic stimulation, external trigeminal nerve stimulation, remote electrical neuromodulation, and non-invasive vagal nerve stimulation), calcitonin gene-related peptide (CGRP) pathway antagonists (anti-CGRP monoclonal antibodies and gepants), psychological therapies, and manual therapies (acupuncture, craniosacral therapy, massage and physical therapy, and spinal manipulation).

Perceived stress and pain severity in individuals with chronic migraine: A longitudinal cohort study using daily prospective diary data.

OBJECTIVE: We aimed to describe patterns of peak attack severity from day-to-day, and in relation to same-day perceived stress, in individuals with chronic migraine (CM). BACKGROUND: Although changes in perceived stress are often believed to trigger attacks, little is known about the relationship between perceived stress and attack severity, and about the role of perceived stress in the day-to-day experience of individuals with CM, as opposed to those with less frequent attacks. METHODS: This was an observational prospective longitudinal cohort study among adults with CM. Daily data about headache, symptoms, and lifestyle factors were collected using the N1-Headache™ digital health platform for 90 days. Days were classified as "migraine days" when a headache occurred that met the International Classification of Headache Disorders criteria. Perceived stress was measured using a 0-10 rating scale. On migraine days, peak pain severity was recorded on a four-point categorical pain scale. Participant-level plots of daily peak severity, colored by perceived stress score, were generated. The relationship between peak severity and perceived stress was also modeled and adjusted for sex, age, continuous headache, presence of menstrual bleeding, day of the week, and disability. RESULTS: Data on 136 participants with 8216 migraine days were analyzed. Sixty-nine percent (94/136) of participants reported the same peak severity on the majority (≥50%) of their migraine days. For every one unit increase in perceived stress, the odds of reporting a higher peak severity were 10% higher (adjusted OR [95% CI] = 1.10 [1.07-1.14]). The inclusion of random effects for the intercept and slope improved the model and demonstrated that there were large differences in individuals' reporting of peak severity and in the relationship between perceived stress and peak severity. CONCLUSION: Individuals with CM report distinct patterns of peak severity from day-to-day. Although overall higher perceived stress was associated with higher peak severity, there is a substantial amount of variation between individuals in this relationship.

The current state of headache medicine education in the United States and Canada: An observational, survey-based study of neurology clerkship directors and curriculum deans.

OBJECTIVE: To investigate the current headache medicine education paradigm in allopathic and osteopathic medical schools in the United States and Canada. BACKGROUND: There is a disparity in the number of clinicians specially trained to treat patients with headache disorders and the number of people who have them. Early education and exposure to headache medicine is crucial to address this disparity. However, the current state of headache education within medical schools across the United States and Canada is unknown. METHODS: The authors created a medical student headache education survey, which is a 20-question REDCap survey that was distributed via email to the neurology clerkship director, curriculum dean, or similar role at each US and Canadian MD or DO conferring medical school. The email listserv was created using the American Academy of Neurology Clerkship Directory, the Association of American Medical Colleges Organization Directory, the American Association of College of Osteopathic Medicine Organization Directory, manual searches of the institutions' websites, and phone calls and emails to administrators as needed. RESULTS: Of the 249 individuals contacted, 78 completed the survey, yielding a response rate of 31.3%. Of those responses, 84.6% of respondents (66/78) reported that their institution has at least one mandatory session on headache disorders. Many of these sessions (72.7% (48/78)) occurred during preclinical training, and 74.2% (49/78) occurred as part of the clinical curricula. Of respondents, 44.9% (39/78) reported that their institutions coordinate headache education across training levels (i.e., from preclinical to clinical), and only 17.9% (14/78) coordinate across clinical rotations. The most common topics covered were headache red flags, migraine, pharmacologic management, and differentiating primary versus secondary headache. 65.4% of respondents (51/78) felt that the preclinical headache curriculum prepares their students for the clinical experience, and 55.1% (43/78) felt that medical students were learning enough about headache medicine at their institution. Barriers to educating medical students about headache included insufficient time during courses, lack of administrative support in curricula development, lack of available resources, and lack of student interest. Case-based learning modules and online lectures were the most desired educational materials to improve medical student headache education at their institution. CONCLUSIONS: The majority of medical schools report incorporating headache medicine education into preclinical or clinical curricula and cover a range of topics in headache medicine. Yet there remains a lack of consistency, with some reporting limited headache education, citing barriers such as lack of administrative support and available educational resources. There is also variation in what is being taught at the medical student level. Future projects should aim to address said barriers, with the goal of providing a standardized headache medicine curriculum for use across medical schools.

Patterns of Perceived Stress Throughout the Migraine Cycle: A Longitudinal Cohort Study Using Daily Prospective Diary Data.

OBJECTIVES: To describe patterns of perceived stress across stages of the migraine cycle, within and between individuals and migraine episodes as defined for this study. METHODS: Individuals with migraine aged ≥18 years, who were registered to use the digital health platform N1-HeadacheTM , and completed 90 days of daily data entry regarding migraine, headache symptoms, and lifestyle factors were eligible for inclusion. Perceived stress was rated once a day at the participant's chosen time with a single question, "How stressed have you felt today?" with response options graded on a 0-10 scale. Days were categorized into phases of the migraine cycle: Ppre  = pre-migraine headache (the 2 days prior to the first day with migraine headache), P0  = migraine headache days, Ppost  = post-migraine headache (the 2 days following the last migraine day with migraine headache), and Pi  = interictal days (all other days). Episodes, defined as discrete occurrences of migraine with days in all 4 phases, were eligible if there was at least 1 reported daily perceived stress value in each phase. Individuals with ≥5 valid episodes, and ≥75% compliance (tracking 90 days in 120 calendar days or less) were eligible for inclusion in the analysis. RESULTS: Data from 351 participants and 2115 episodes were included in this analysis. Eighty-six percent of the sample (302/351) were female. The mean number of migraine days per month was 6.1 (range 2-13, standard deviation = 2.3) and the mean number of episodes was 6.0 (range 5-10, standard deviation = 1.0) over the 90-day period. Only 8 (8/351, 2.3%) participants had chronic migraine (defined as 15 or more headache days per month with at least 8 days meeting criteria for migraine). Cluster analysis revealed 3 common patterns of perceived stress variation across the migraine cycle. For cluster 1, the "let down" pattern, perceived stress in the interictal phase (Pi ) falls in the pre-headache phase (Ppre ) and then decreases more in the migraine phase (P0 ) relative to Pi . For cluster 2, the "flat" pattern, perceived stress is relatively unchanging throughout the migraine cycle. For cluster 3, the "stress as a trigger/symptom" pattern, perceived stress in Ppre increases relative to Pi , and increases further in P0 relative to Pi . Episodes were distributed across clusters as follows: cluster 1: 354/2115, 16.7%; cluster 2: 1253/2115, 59.2%, and cluster 3: 508/2115, 24.0%. Twelve participants (12/351, 3.4%) had more than 50% of their episodes fall into cluster 1, 216 participants (216/351, 61.5%) had more than 50% of their episodes fall into cluster 2, and 25 participants (25/351, 7.1%) had more than 50% of their episodes fall into cluster 3. There were 40 participants with ≥90% of their episodes in cluster 2, with no participants having ≥90% of their episodes in cluster 1 or 3. CONCLUSIONS: On an aggregate level, perceived stress peaks during the pain phase of the migraine cycle. However, on an individual and episode basis, there are 3 dominant patterns of perceived stress variation across the migraine cycle. Elucidating how patterns of perceived stress vary across the migraine cycle may contribute insights into disease biology, triggers and protective factors, and provide a framework for targeting individualized treatment plans.

Internalizing Symptoms in Pediatric Migraine: A Systematic Review Protocol.

OBJECTIVES: The primary objective of the proposed systematic review is to determine if there is an association between internalizing disorders and symptoms (ie, subclinical symptoms) and migraine in children and adolescents. METHODS: We will perform a peer-reviewed Peer Review of Electronic Search Strategies search of MEDLINE, Embase, PsycINFO, and CINAHL from inception to December 2019. The authors will also review all reference lists of included studies for relevant citations. Observational studies on the association of pediatric migraine with internalizing disorders and symptoms will be included in this review. Case-control, cohort, and cross-sectional studies that include participants aged 18 years and under will be eligible for inclusion. The primary outcome for this systematic review will be migraine and the exposures of interest will include internalizing disorders (eg, major depressive disorder, dysthymia, generalized anxiety disorder, and post-traumatic stress disorder) and internalizing symptoms (depression symptoms, anxiety symptoms, obsessive compulsive symptoms, and post-traumatic stress symptoms). Two investigators will independently carry out an initial screen of abstracts, followed by a second screen of full-text manuscripts. Data extraction will be completed by 2 independent investigators. Study quality will be assessed using the Newcastle-Ottawa criteria for case-control and cohort studies and using a modified version of the Newcastle-Ottawa criteria for cross-sectional studies. A narrative synthesis of the data will be provided and, if possible, data will be quantitatively summarized using appropriate meta-analytic methods. Throughout the manuscript, the Preferred Reporting Items for Systematic Review and Meta-Analysis reporting standards will be followed. RESULTS: The goal of this systematic review will be to provide a narrative, and if possible, quantitative summary on the association between pediatric migraine and internalizing disorders and symptoms. CONCLUSIONS: The methods applied in this systematic review protocol can be used to inform the design of future systematic reviews of observational studies in headache medicine. The results of this systematic review will be used to inform the clinical community on the association between pediatric migraine and internalizing disorders and symptoms and may also be used to inform the design of future research studies in this area.

The Profile and Prognosis of Youth With Status Migrainosus: Results From an Observational Study.

OBJECTIVE: To characterize the clinical features of a large sample of children, adolescents, and young adults with a history of status migrainosus (SM) and to describe their short-term prognosis. BACKGROUND: Data on the clinical characteristics of children and adolescents with SM are sparse and little is known about the prognosis of this population. METHODS: This was a retrospective clinical cohort study that included patients from the Cincinnati Children's Headache Center if they had a diagnosis of migraine and data available for a 1-3 months follow-up interval. Data extracted from the initial interval visit (visit A) included: age, sex, race, migraine diagnosis, SM history, chronic migraine, medication overuse headache (MOH), body mass index (BMI), headache frequency, headache severity, disability, allodynia and lifestyle habits: caffeine intake, meal skipping, sleep duration, exercise frequency, and fluid intake. Data extracted from the initial consultation visit included: months with headache at initial consultation visit, patient endorsing "feeling depressed" and anxiety symptoms. Headache frequency and visit type were also measured at the second visit (visit B) in the follow-up interval. A multivariate logistic regression model with a backward elimination procedure was created to model the odds of having a diagnosis of SM using the cross-sectional predictor variables above. Second, chi-square tests were used to compare the proportion of patients with SM to the proportion of patients without SM who had each of the following outcomes in the short-term follow-up window: treatment response (50% or greater reduction in headache frequency), overall reduction in headache frequency (reduction of 1 or more headache days/month), minimal change in headache frequency (increase in 0-3 headache days/month), and clinical worsening (increase in 4 or more headache days/month). RESULTS: A total of 5316 youth with migraine were included and 559 (10.5%) had a history of SM. In the multivariate logistic regression model, predictors significantly associated with SM were: older age (OR = 1.13, 95% CI = 1.09-1.17, P < .0001), migraine with aura (MWA) (OR = 1.30, 95% CI = 1.03-1.65, P = .03), MOH (OR = 1.72, 95% CI = 1.30-2.28, P = .0001), headache frequency (OR = 0.99, 95% CI = 0.97-0.99, P = .030), higher headache severity (OR = 1.08, 95% CI = 1.02-1.15, P = .009), months with headache at initial consultation (OR = 1.00, 95% CI = 1.00-1.01, P = .042), and admission to infusion center at visit B (OR = 2.27, 95% CI = 1.38-3.72, P = .001). Patients with a history of SM were more likely to experience an increase in 4 or more headache days per month at follow-up: 15.2% as compared to 11.1% of those without SM, χ2 (1, n = 5316) = 8.172, P = .0043. CONCLUSIONS: Youth with SM represent a distinct subgroup of the migraine population and have an unfavorable short-term prognosis.

Family Perspectives on Visiting the Pediatric Emergency Department for Migraine: A Qualitative Study.

OBJECTIVE: The aim of this study was to explore the perspectives of families regarding their expectations and experience of visiting the emergency department (ED) for migraine. METHODS: This was a qualitative study involving the families of 25 patients aged 10 to 18 years receiving ED care for acute migraine. Following their visit, independent semistructured telephone interviews were conducted with both the patient and parent or guardian. Questions were designed to explore factors pertaining to the family's perspective regarding their visit to the ED and expectations for the ED visit. RESULTS: Families reported a variety of reasons for visiting the ED. The majority of participants reported that they were worried about their headaches. Families more commonly had expectations for treatment than they did for investigations. As compared with patients, parents more commonly reported specific expectations for investigations and less commonly expressed concerns about intravenous treatments. Expectations for treatment efficacy varied: whereas some parents expected complete pain relief, for others, lesser degrees of relief were considered satisfactory. The experience of treatment efficacy was related to willingness to receive the same treatment again. CONCLUSIONS: Given that a high frequency of families endorsed that they were worried about the headache when presenting to the ED, clinicians should strive to make a diagnosis of migraine in the ED setting and to educate families about this diagnosis. Because of divergent parent and patient perspectives, health care providers should inquire about family expectations, especially in relation to expectations for investigations and concerns surrounding intravenous interventions, and ensure that both the patient's and parent's perspectives are considered when developing a management plan for pediatric migraine.

Early Life Stress in Adolescent Migraine and the Mediational Influence of Symptoms of Depression and Anxiety in a Canadian Cohort.

OBJECTIVE: This study sought to examine the association between early life stressors and adolescent headache in the Canadian population, and the potential mediating influence of symptoms of depression and anxiety. BACKGROUND: Early life stress or adverse childhood experiences have a well-documented association with migraine and headache in adulthood, as do symptoms of depression and anxiety. However, there is limited evidence examining the relationship between early life environmental stressors and adolescent headache, and a lack of longitudinal research. Family-level factors including parenting behaviors and parental influences such as maternal distress have been implicated in pediatric chronic pain. METHODS: This study used data from 2313 respondents of the National Longitudinal Survey of Children and Youth, followed prospectively from age 0 to 1 years at baseline (1994/1995) until age 14 to 15 years (2008/2009). The relationships between 4 measures of early life family level stressors, and outcomes of incident health professional-diagnosed migraine and self-reported, unclassified frequent headache (>1 per week) were examined. We conducted a series of mediation analyses of the indirect effect (IE) of family-level stressors on headache outcomes through symptoms of depression and anxiety in late childhood. The IE and 95% bias-corrected confidence interval (CIBC ) were estimated using maximum likelihood logistic regression methods (log odds scale). RESULTS: The proportion of respondents with incident migraine and frequent headache was 3.1% and 11.1%, respectively. There were no direct associations between distal early life family-level factors and adolescent headache. Symptoms of depression- and anxiety-mediated relationships between family dysfunction (IE 0.0181, 95% CIBC 0.0001-0.0570), punitive parenting (IE 0.0241, 95% CIBC 0.0015-0.0633), parental depressive symptomatology (IE 0.0416, 95% CIBC 0.0017-0.0861), and incident migraine but not frequent headache. Indirectly, presence of family dysfunction, punitive parenting, and higher parental depressive symptomatology in early life were associated with a greater likelihood of migraine in adolescence, through greater symptoms of depression and anxiety in late childhood. CONCLUSIONS: Findings provide support for the influence of early life family-level factors on prospective risk of developing migraine, through symptoms of depression and anxiety. Addressing family dynamics in clinical practice may reduce unnecessary stress-related burdens on children and adolescents, which could lead to improvements in their somatic complaints.