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Objectives: We used Cluster Analysis of Migraine‐associated Symptoms (CAMS) to critically evaluate current International Classification of Headache Disorders‐Third Edition (ICHD‐3) migraine‐associated symptoms criteria. Background: Diagnostic criteria play a central role in guiding clinical trial inclusion, and therefore available treatments. Migraine and tension‐type headaches (TTH) are differentiated in ICHD‐3 by many headache characteristics, including associated symptoms. A diagnosis of probable migraine indicates some but not all features of migraine are met. Photophobia and phonophobia, or nausea and/or vomiting, are required to meet a diagnosis of migraine; however, CAMS—a model that describes associated symptoms across youth with headache—indicates that a broader range of symptoms contain information about migraine burden. Methods: In this multisite retrospective cross‐sectional study, we evaluated ICHD‐3 migraine criteria. Youth aged 6–17 years with migraine (including probable migraine) or TTH were included in the analysis. We used CAMS to evaluate the migraine‐associated symptom criterion. With CAMS as a guide, we evaluated how changes to the migraine‐associated symptom criterion altered who met the diagnosis of migraine. Results: Of the 9017 participants included in this study, 66.7% were female and had a median (interquartile range) age of 13 (10–15) years. Most participants had migraine or probable migraine (99.0%), and the remainder had TTH (1.0%). A sizable percentage (10.1%) of youth under the umbrella diagnosis of migraine were diagnosed with probable migraine because they did not meet migraine‐associated symptom criterion D; however, many in this group reported several non‐ICHD migraine‐associated symptoms. We explored alterations to criterion D based on CAMS. Allowing for photophobia or phonophobia re‐categorized 55.6% of youth as having migraine, though some only had one symptom. Including lightheadedness or lightheadedness and spinning re‐categorized 19.7% and 25.8% of youth with migraine, respectively, but all of those who were re‐categorized had at least two migraine‐associated symptoms. Conclusion: The ICHD‐3 captures the most prevalent migraine‐associated symptoms; however, many youths with probable migraine who do not meet full criteria due to insufficient associated symptoms nonetheless experience multiple non‐ICHD migraine‐associated symptoms. Changes to criterion D should be considered for the ICHD‐4. Plain Language Summary: For clinicians to make a diagnosis of migraine based on International Classification of Headache Disorders‐Third Edition (ICHD‐3) criteria, patients must have headache‐associated nausea, vomiting, or light and sound sensitivity (criterion D). However, migraine can also be associated with other symptoms like lightheadedness, difficulties with thinking, and vertigo. In this study of youth aged 6–17 years with migraine, probable migraine, or tension‐type headache, we looked at how altering the ICHD‐3 criterion D changed participants' diagnosis based on their symptoms; overall, our results suggest that the next version of ICHD should account for the fact that many youth who do not experience nausea, vomiting, or light and sound sensitivities still experience manyx other migraine associated symptoms. [ABSTRACT FROM AUTHOR]

Objective: To conduct a retrospective cross‐sectional multicenter study to validate the relationships between migraine‐associated symptoms. Background: Symptoms associated with headache—photophobia and phonophobia, nausea, and/or vomiting—are required criteria for migraine diagnosis based on the International Classification of Headache Disorders‐Third Edition (ICHD‐3). However, individuals with migraine report high rates of other symptoms (e.g., lightheadedness, difficulty thinking). We recently completed a single‐center study assessing the relationships between an expanded set of migraine‐associated symptoms. Methods: A pre‐registered cross‐sectional multicenter retrospective analysis was conducted on standardized questionnaire data of youth ages 6–17 years from two headache registries at pediatric tertiary care centers. Cluster Analysis of Migraine‐associated Symptoms (CAMS) was implemented to assess associations between 11 migraine‐associated symptoms. We explored differences between the two centers, and how CAMS was associated with demographics, including sex and age, and headache burden. Results: There were 10,721 participants who were 66.5% female and had a median (interquartile range) age of 13 (10–15) years. The first three CAMS dimensions accounted for 46.5% of the variance and were consistent across sites. The first dimension indicated those reporting any migraine‐associated symptoms were likely to report multiple. The second dimension separated symptoms into those included in ICHD‐3 migraine diagnostic criteria and non‐ICHD symptoms (e.g., lightheadedness, difficulty thinking). The third dimension separated sensory hypersensitivity and vestibular symptoms. An abundance of migraine‐associated symptoms correlated with greater headache severity (Spearman's ρ = 0.18, 95% confidence interval [CI] 0.17–0.20; small effect size) and disability (ρ = 0.26, 95% CI 0.25–0.28; small effect size). We also observed differences in associated symptoms across age and sex. Discussion: Associations between an expanded set of migraine‐associated symptoms are informative for headache burden and reveal intriguing changes across child development and sex. We were able to replicate findings across two centers, indicating that these symptom clusters are inherent to migraine. Plain Language Summary: The presence of symptoms such as light or sound sensitivity, nausea, and vomiting can help clinicians differentiate between migraine and other headache disorders, such as tension‐type headache. However, people with migraine commonly experience symptoms that are not part of migraine diagnostic criteria per the International Classification for Headache Disorders‐Third Edition criteria, including lightheadedness, vision changes, and vertigo. In this study, we found that by considering these other associated symptoms, we were able to better understand the burden of headache in children and adolescents; e.g., we found that having more associated symptoms was associated with more headache severity and greater headache impact in children and teenagers. [ABSTRACT FROM AUTHOR]

Objective: To qualitatively and quantitatively summarize the evidence for the use of onabotulinumtoxinA injections in children and adolescents with migraine. Background: There are limited evidence‐based treatment options for youth with migraine, especially youth with chronic migraine (CM). OnabotulinumtoxinA injections are an established evidence‐based treatment for adults with CM. While several studies have assessed their safety and efficacy among adolescents with CM, there are no published systematic reviews summarizing the pediatric evidence. Methods: We carried out a systematic review, reported according to the Preferred Reporting Items for Systematic Review and Meta‐Analysis, aiming to identify studies that included five or more children and adolescents aged ≤18 years with a diagnosis of migraine, who were treated with ≥50 units (U) of onabotulinumtoxinA and had outcomes assessed ≥4 weeks after one or more injection cycle. Both observational studies and randomized controlled trials (RCTs) were eligible for inclusion. Two investigators independently carried out the first (titles and abstracts) and second (full text) screening stages, as well as data extraction and quality appraisal. The American Academy of Neurology risk of bias grading scheme was used to assess study risk of bias. Studies with adequate data were pooled using random effects meta‐analyses, and Hedge's g standardized mean differences with 95% confidence intervals (CIs) were generated to estimate the effect sizes of the continuous outcomes included. Studies lacking data required for meta‐analysis were summarized qualitatively. Results: We screened 634 studies and included 14 studies comprising 491 participants, of whom 489 had CM. Two studies were RCTs, 12 were observational uncontrolled studies, and all but one study included only youth with CM. Five Class IV observational uncontrolled studies were amenable to pooling in meta‐analyses. After a mean of 2–2.6 injection cycles, headache frequency was shown to decrease significantly after treatment with onabotulinumtoxinA (Hedge's g = 0.97, 95% CI 0.58–1.35; p < 0.0001), as did severity (Hedge's g = 1.24, 95% CI 0.55–1.94; p = 0.0005), with both estimates having a large effect size magnitude. A Class I parallel‐group RCT of one injection series (155 U, 74 U, or placebo), powered to detect a change in 4 headache days per month, did not find outcome differences between the active and placebo treatment arms. A Class IV crossover RCT showed superiority of active (155 U) versus placebo injections. The remaining Class IV observational studies that were excluded from the meta‐analyses all showed improved outcomes with onabotulinumtoxinA injections over time. No serious adverse events related to treatment occurred. Conclusion: OnabotulinumtoxinA injections have established safety for use in children and adolescents with CM and are likely effective in reducing headache frequency and severity over time. However, in the absence of an adequately powered parallel‐group RCT assessing the efficacy of multiple injection cycles, it remains unclear if this intervention is superior to placebo. Plain Language Summary: The results of our review suggest that onabotulinumtoxinA injections are safe and that they are likely effective for children and adolescents with chronic migraine. However, the available research is generally biased because of study design issues, and it is still uncertain if onabotulinumtoxinA injections have benefits above and beyond the benefits of placebo injections for children and adolescents. Better‐designed research is required to understand if onabotulinumtoxinA injections are more effective than placebo injections in treating children and adolescents with chronic migraine. [ABSTRACT FROM AUTHOR]

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. Plain Language Summary: People with chronic migraine (CM) have a high frequency of attacks (≥15 days/month), yet little is known about their day‐to‐day experience of pain. We looked at the relationship between 12 clinical factors, including mood, sleep, stress, and day‐to‐day pain severity scores in adults with CM. We found that people's experience of pain severity and its relationship to different clinical factors was very individualized, with a lot of variability between people. [ABSTRACT FROM AUTHOR]

The article focuses on investigating clinical outcomes among youth with continuous headache, revealing improvements in headache status within 3–4 months after receiving multidisciplinary treatment, despite moderate average headache severity. It is discussed that treatment utilization shifted towards increased use of pill-based preventive treatments and decreased engagement in nonpharmacologic strategies, highlighting potential treatment preferences and priorities among this population.

Objective: To examine trends in diagnosis of headache and migraine in a large pediatric neurology cohort, and test whether an electronic health record (EHR)‐integrated headache questionnaire can increase specificity of diagnosis and likelihood of prescribing migraine treatment. Background: Under‐diagnosis of migraine contributes to the burden of disease. As we founded our Pediatric Headache Program in 2013, we recognized that the proportion of patients with headache who were given a diagnosis of migraine was much lower than expected. Methods: We developed a patient headache questionnaire, initially on paper (2013–2014), then in an electronic database (2014–2016), and finally integrated into our electronic health record (pilot: 2016, full: May 2017). We compared diagnoses and prescribed treatments for new patients who were given a headache diagnosis, looking at trends in the proportion of patients given specific diagnoses (migraine, etc.) versus the non‐specific diagnosis, "headache." Next, we conducted a prospective cohort study to test for association between provider use of the form and the presence of a specific diagnosis, then for an association between specific diagnosis and prescription of migraine treatment. Results: Between July 2011 and December 2022 the proportion of new headache patients who were given a diagnosis of migraine increased 9.7% and non‐specific headache diagnoses decreased 21.0%. In the EHR cohort (June 2017–December 2022, n = 15,122), use of the provider form increased the rate of specific diagnosis to 87.2% (1839/2109) compared to 75.5% (5708/7560) without a patient questionnaire, nearly doubling the odds of making a specific diagnosis (odds ratio [OR] 1.90, 95% confidence interval [CI]: 1.65–2.19). Compared to those given only a non‐specific headache diagnosis who were prescribed a migraine therapy 53.7% (1766/3286) of the time, 75.3% (8914/11836) of those given a specific diagnosis received a migraine therapy, more than doubling the odds of prescription (OR 2.39, 95% CI: 2.20–2.60). Conclusions: Interventions to improve specificity of diagnosis were effective and led to increased rates of prescription of migraine treatments. These results have been sustained over several years. This headache questionnaire was adapted into the Foundation system of EpicCare, so it is broadly available as a clinical and research tool for institutions that use this EHR software. [ABSTRACT FROM AUTHOR]

Background: Youth with continuous (always present) headache are vastly understudied; much remains to be understood regarding treatment response in this population. Objective: To describe and explore biopsychosocial factors related to initial clinical outcomes among treatment‐seeking youth with continuous headache. Methods: This retrospective cohort study extracted data of 782 pediatric patients (i.e., aged <18 years) with continuous headache from a large clinical repository. Youth in this study had experienced continuous headache for ≥1 month before presenting to a multidisciplinary headache specialty clinic appointment. Extracted data from this appointment included patients' headache history, clinical diagnoses, and headache‐related disability, as well as information about biopsychosocial factors implicated in headache management and/or maintenance (e.g., healthy lifestyle habits, history of feeling anxious or depressed). Additional data regarding patient headache characteristics, disability, and lifestyle habits were extracted from a subset of 529 youth who returned to clinic 4–16 weeks after their initial follow‐up visit. After characterizing initial treatment response, exploratory analyses compared youth with the best and worst treatment outcomes on several potentially influential factors. Results: Approximately half of youth (280/526; 53.2%) continued to have continuous headache at follow‐up, ~20% of youth (51/526) reported a significant (≥50%) reduction in headache frequency. Improvements in average headache severity (e.g., percentage with severe headaches at initial visit: 45.3% [354/771]; percentage with severe headaches at follow‐up visit: 29.8% [156/524]) and headache‐related disability were also observed (e.g., percentage severe disability at initial visit: 62.9% [490/779]; percentage severe disability at initial follow‐up visit: 34.2% [181/529]). Individuals with the worst headache frequency and disability had a longer history of continuous headache (mean difference estimate = 5.76, p = 0.013) and worse initial disability than the best responders (χ2[3, 264] = 23.49, p < 0.001). They were also more likely to have new daily persistent headache (χ2[2, 264] = 12.61, p = 0.002), and were more likely to endorse feeling depressed (χ2[1, 260] = 11.46, p < 0.001). Conclusion: A notable percentage of youth with continuous headache show initial improvements in headache status. Prospective, longitudinal research is needed to rigorously examine factors associated with continuous headache treatment response. [ABSTRACT FROM AUTHOR]

Objective: To examine group differences in self‐reported migraine days among youth who completed the Childhood and Adolescent Migraine Prevention (CHAMP) trial prior to its closure and explore the relationship between self‐reported and "nosology‐derived" (i.e., International Classification of Headache Disorders, 3rd edition [ICHD‐3]) migraine days. Background: The CHAMP trial compared amitriptyline and topiramate to placebo for migraine prevention in youth and proposed to analyze change in migraine days as a secondary outcome. There is considerable variability in the field regarding what constitutes a "migraine day," how this is determined and reported in trials, and how consistent these measures are with diagnostic nosology. Methods: CHAMP trial completers (N = 175) were randomized to receive amitriptyline (n = 77), topiramate (n = 63), or placebo (n = 35). Participants maintained daily headache diaries where they reported each day with headache and if they considered that headache to be a migraine. For each headache day, participants completed a symptom record and reported about symptoms such as pain location(s) and presence of nausea/vomiting or photophobia and phonophobia. We examined group differences in self‐reported migraine days at trial completion (summed from trial weeks 20–24) compared to baseline. We also used an algorithm to determine whether participants' symptom reports met ICHD‐3 criteria for migraine without aura, and examined the association between self‐reported and "nosology‐derived" migraine days. Results: Results showed no significant differences between groups in self‐reported migraine days over the course of the trial. Self‐reported and "nosology‐derived" migraine days during the baseline and treatment phases were strongly associated (r's = 0.73 and 0.83, respectively; p's < 0.001). Conclusion: Regardless of treatment, CHAMP trial completers showed clinically important reductions in self‐reported migraine days over the course of the trial (about 3.8 days less). The strong association between self‐reported and "nosology‐derived" migraine days suggests youth with migraine can recognize a day with migraine and reliably report their headache features and symptoms. Greater rigor and transparency in the calculation and reporting of migraine days in trials is needed. [ABSTRACT FROM AUTHOR]

Objective: To assess agreement for migraine day between self‐report and diagnostic guidelines for children and adolescents using a headache diary. Background: Trial guidelines recommend prospective collection of headache features and adoption of migraine day as an outcome measure, but there is no clear consensus on the definition of migraine day. Methods: This is a secondary analysis of data from two projects—a prospective cohort study validating a pediatric scale of treatment expectancy and a clinical trial of occipital nerve blocks to treat status migrainosus. Participants completed a text message‐based diary for 4 or 12 weeks (depending on treatment), and a detailed headache assessment on a random 20% of headache days. Using this assessment, we determined whether a headache day qualified for migraine or probable migraine, based on the International Classification of Headache Disorders, 3rd edition (ICHD‐3). Results: Of 122 enrolled children and adolescents, 106 (86.9%) completed ≥1 detailed headache assessment (438 entries). We found moderate agreement between self‐reported and ICHD‐derived migraine day, with a Cohen's Kappa of 0.50 (positive predictive value [PPV]: 0.66; negative predictive value [NPV]: 0.85; correlation: 0.51). Allowing for ICHD‐derived probable migraine significantly increased PPV (0.66 vs. 0.94; 95% CI: 0.57–0.74 vs. 0.90–0.97), but decreased NPV (0.85 vs. 0.293; CI: 0.77–0.90 vs. 0.199–0.40), Cohen's Kappa (0.50 vs. 0.237; CI: 0. 389–0.60 vs. 0.139–0.352), and correlation (r = 0.51 vs. 0.302; CI: 0.41–0.61 vs. 0.192–0.41). Pain severity (OR: 5.7; CI: 2.39–13.8), photophobia (OR: 4.1; CI: 1.02–16.6), and phonophobia (OR: 7.5; CI: 1.95–29.3) were significantly associated with participants' perception of migraine. Conclusion: We found only moderate agreement between self‐reported and ICHD‐derived migraine day, suggesting both measures are not equal but may represent overlapping aspects of migraine as a disease. This highlights the difficulty of applying ICHD criteria to individual attacks. We recommend greater methodological transparency in future research to avoid readers conflating both measures. [ABSTRACT FROM AUTHOR]

Objective: This case‐control study examines if measures of subjective and objective (actigraphic) sleep difficulties mediate alterations in amygdalar connectivity in adolescents with migraine compared to healthy adolescents. Background: Adolescents with migraine have different functional connectivity of the amygdala compared to individuals without migraine. Sleep is often disturbed in adolescents with migraine, and could contribute to the alterations in functional connectivity. Methods: Twenty adolescents with migraine and 20 healthy controls were recruited from Cincinnati Children's Hospital. Participants completed surveys about their headaches and overall sleep quality, sleep hygiene, and perceived sleep difficulties (Insomnia Severity Scale [ISI]); completed wrist‐worn actigraphy; and underwent a magnetic resonance imaging scan. Results: Adolescents with migraine differed from healthy controls only in perceived difficulty in sleep initiation and maintenance (ISI: 8.5 ± 4.7 and 4.5 ± 3.7 [mean ± standard deviation], −4.00 [95% confidence: −6.7 to −1.3], p = 0.005) and had greater functional connectivity between the amygdala and the posterior cingulate cortex, precuneus, dorsolateral prefrontal, sensorimotor, and the occipital cortexes. The differences in functional connectivity of the amygdala were not mediated by the subjective/objective sleep measures (ISI/wake minutes after sleep onset). Conclusions: Adolescents with migraine have greater connectivity between the amygdala and areas involved in sensory, affective, and cognitive aspects of pain. These alterations may not be due to higher levels of sleep difficulties in adolescents with migraine, suggesting that both amygdala and sleep alterations may play an independent role in migraine pathophysiology. This advances the understanding of the mechanisms underlying pediatric migraine and can potentially advance migraine management. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To compare spatial pain modulation capabilities between adolescents with and without migraine. Background: Conditioned pain modulation (CPM) responses at the leg are similar in adolescents with versus without migraine. However, the anatomical region of testing may affect spatial pain modulation capabilities as differences in nociceptive processing between patients with migraine and healthy controls are found in local areas that are near the site of clinical pain but not in nonlocal areas. This study aimed to examine spatial pain modulation capabilities tested by the CPM paradigm using test stimulus applied to a local body area. Methods: Nineteen adolescents with migraine (age 14.9 ± 2.3, mean ± SD; 16 female) and 20 healthy adolescents (age 13.8 ± 2.5, mean ± SD; 16 female) completed this case–control study at Cincinnati Children's Hospital Medical Center. Pressure pain thresholds (PPT) were assessed at the trapezius before and during immersion of the foot in a cold water bath (8°C). Results: In the migraine group (146.0 ± 79.1, mean ± SD), compared to healthy controls (248.0 ± 145.5, mean ± SD), significantly lower PPT (kilopascal) values were found (estimate = 124.28, 95% CI: 58.98, 189.59, p < 0.001; effect size: d = 1.40). No differences between the groups were found for pain intensity and unpleasantness ratings of cold‐water immersion nor the CPM response. Conclusions: This study found altered ascending nociceptive processing of mechanical stimuli at the neck in adolescents with migraine. However, endogenous pain modulatory mechanisms were functional and not altered. In light of other studies, impairments in inhibitory control may not be involved in migraine pathophysiology in pediatric patients regardless of stimulus location. [ABSTRACT FROM AUTHOR]

Objectives: Migraine is a common disabling neurological disorder. Current acute treatments for migraine in adolescents are mostly pharmacological and may have limited effectiveness, can cause side effects, and may lead to medication overuse. There is an unmet need for effective and well‐tolerated treatments. Remote electrical neuromodulation (REN) is a novel acute treatment of migraine that stimulates upper arm peripheral nerves to induce conditioned pain modulation (CPM)—an endogenous analgesic mechanism. The REN device (Nerivio®, Theranica Bio‐Electronics Ltd., Israel) is a FDA‐authorized device for acute treatment of migraine in adults. This study assessed the efficacy and safety of REN in adolescents with migraine. Design and Methods: This was an open‐label, single‐arm, multicenter study in adolescents (ages 12–17 years) with migraine. Participants underwent a 4‐week run‐in phase. Eligible participants continued to an 8‐week treatment phase with the device. Pain severity, associated symptoms, and functional disability were recorded at treatment initiation, and 2 and 24 hours post‐treatment. The primary endpoints of this study were related to the safety and tolerability of REN. The secondary endpoints were related to device efficacy and included the proportion of participants who achieved pain relief at 2 hours post‐treatment and the proportion of participants who achieved pain freedom at 2 hours. The presented results reflect an interim analysis with subsequent stopping of the rest of the study. Results: Sixty participants were enrolled for the study; of these, 14 failed to meet the run‐in criteria and 1 was lost to follow‐up. Forty‐five participants performed at least one treatment, of which 39 participants completed a test treatment with REN. One device‐related adverse event (2%) was reported in which a temporary feeling of pain in the arm was felt. Pain relief and pain‐free at 2 hours were achieved by 71% (28/39) and 35% (14/39) participants, respectively. At 2 hours, 69% (23/33) participants experienced improvement in functional ability. Conclusions: REN may offer a safe and effective non‐pharmacological alternative for acute treatment in adolescents. [ABSTRACT FROM AUTHOR]

Objectives: This basic mechanistic study examined the changes in brain activation and resting‐state connectivity after 8 weeks of CBT in youth with migraine. Background: Cognitive behavioral therapy (CBT) is a psychological intervention that is effective in reducing pain in migraine patients. However, the neural mechanisms underlying CBT in adolescents with migraine are not yet known. Methods: Eighteen adolescents with migraine (15 females, age 15.1 ± 2.1 years [mean ± SD]) completed 8 weekly CBT sessions. Before the first and after the final CBT session, participants underwent structural and resting‐state blood‐oxygen‐level‐dependent contrast MRI scans. Arterial spin labeling was also used to examine brain activation during the resting state. For connectivity analyses, the right and left amygdala were chosen as seed regions. Relationships of the time courses within these seeds with voxels across the whole brain were evaluated. Results: Headache frequency decreased from 15 ± 7.4 headaches per month before CBT to 10 ± 7.4 after CBT (P <.001). After CBT, greater brain activations in frontal regions involved in cognitive regulation of pain were found. In addition, after CBT increased connectivity between the amygdala and frontal regions was observed. Associations between brain activation and amygdalar connectivity with a reduction in headache frequency were also observed. Conclusions: Alterations in brain function and amygdalar connectivity with areas involved in nociceptive processing, cognitive function, and emotional regulation may underlie the ability of CBT to aid in the prevention of headaches in migraine patients. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to design, code, and pilot test the feasibility and preliminary efficacy of a self‐management digital therapeutic tool for adolescents with migraine. Background: Self‐management of migraine in adolescents is complex and has important implications for health outcomes. A comprehensive and accessible approach to self‐management is needed for youth with migraine, their parents, and clinicians. Methods: An iterative co‐design process was used to develop and optimize the Migraine Manager's digital therapeutic self‐management tool. Subsequently, 40 adolescents, age 11‐18 years, were enrolled in an 8‐week single‐arm open label trial (N = 36 analyzed). The primary outcome was headache days. Results: Usage data for Migraine Manager were similar to other health app usage data and feedback from participants was uniformly positive, indicating acceptable feasibility. Preliminary efficacy was demonstrated by a reduction in headache days from 17.2 ± 8.5 at baseline to 7.9 ± 7.2 at 8 weeks (95% CI, −13.0 to −7.8; P <.001). There was also statistically significant improvement in patient physical functioning quality of life reported by both patients (baseline = 55.7 ± 20.4; 8 weeks = 69.7 ± 21.9, P =.005) and parents (baseline = 58.5 ± 22.8; 8 weeks = 74.3 ± 18.1, P =.002), and in parent‐reported ingestion issues subscale of the adherence barriers scale from baseline to 8 weeks (baseline = 6.0 ± 2.6; 8 weeks = 5.2 ± 3.0, P =.020). Conclusions: A self‐management digital therapeutic tool for adolescents with migraine can offer care to patients who might not otherwise receive such services. Migraine Manager demonstrated the feasibility and preliminary efficacy in this pilot trial, highlighting the potential beneficial impact of this tool. Larger controlled trials with long‐term follow‐up are needed to definitively determine the clinical efficacy of Migraine Manager. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

An editorial is presented in which author discusses new guidelines of migraine. Topics discussed include information on guidelines from American Academy of Neurology (AAN) in collaboration with specialty societies has developed a growing number of evaluation and treatment guidelines; challenges of guideline development like finding strength of the evidence of efficacy; and use of the standardized approach of the guideline development.

Objective: To provide evidence‐based recommendations for the acute symptomatic treatment of children and adolescents with migraine. Methods: We performed a systematic review of the literature and rated risk of bias of included studies according to the American Academy of Neurology classification of evidence criteria. A multidisciplinary panel developed practice recommendations, integrating findings from the systematic review and following an Institute of Medicine‐compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence. Results: There is evidence to support the efficacy of the use of ibuprofen, acetaminophen (in children and adolescents), and triptans (mainly in adolescents) for the relief of migraine pain, although confidence in the evidence varies between agents. There is high confidence that adolescents receiving oral sumatriptan/naproxen and zolmitriptan nasal spray are more likely to be headache free at 2 hours than those receiving placebo. No acute treatments were effective for migraine‐related nausea or vomiting; some triptans were effective for migraine‐related phonophobia and photophobia. Recommendations: Recommendations for the treatment of acute migraine in children and adolescents focus on the importance of early treatment, choosing the route of administration best suited to the characteristics of the individual migraine attack, and providing counselling on lifestyle factors that can exacerbate migraine, including trigger avoidance and medication overuse. [ABSTRACT FROM AUTHOR]

Objective: To provide updated evidence‐based recommendations for migraine prevention using pharmacologic treatment with or without cognitive behavioral therapy in the pediatric population. Methods: The authors systematically reviewed literature from January 2003 to August 2017 and developed practice recommendations using the American Academy of Neurology 2011 process, as amended. Results: Fifteen class I‐III studies on migraine prevention in children in adolescents met inclusion criteria. There is insufficient evidence to determine if children and adolescents receiving divalproex, onabotulinumtoxinA, amitriptyline, nimodipine and flunarizine are more or less likely than those receiving placebo to have a reduction in headache frequency. Children with migraine receiving propranolol are possibly more likely than those receiving placebo to have an at least 50% reduction in headache frequency. Children and adolescents receiving topiramate and cinnarizine are probably more likely than those receiving placebo to have a decrease in headache frequency. Children with migraine receiving amitriptyline plus cognitive behavioral therapy are more likely than those receiving amitriptyline plus headache education to have a reduction in headache frequency. Recommendations The majority of randomized controlled trials studying the efficacy of preventive medications for pediatric migraine fail to demonstrate superiority to placebo. Recommendations for the prevention of migraine in children include counseling on lifestyle and behavioral factors that influence headache frequency, and assessment and management of comorbid disorders associated with headache persistence. Clinicians should engage in shared decision making with patients and caregivers regarding the use of preventive treatments for migraine, including discussion of the limitations in the evidence to support pharmacologic treatments. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the short‐term prognosis of a clinical population of pediatric and young adult patients with migraine and explore predictors of clinical worsening while in care. Methods: This was a retrospective study of all migraine patients seen at the Cincinnati Children's Hospital Headache Center from 09/01/2006 to 12/31/2017, who had at least 1 follow‐up visit within 1‐3 months of the index visit analyzed. Included data were: age, sex, race, primary ICHD diagnosis, chronic migraine, medication overuse, history of status migrainosus, BMI percentile, headache frequency, headache severity, PedMIDAS score, allodynia, preventive treatment type, lifestyle habits, disease duration, depressive and anxiety symptoms. Clinical worsening was defined as an increase in 4 or more headache days per month between the index visit and the follow‐up visit. Results: Data for 13,160 visit pairs (index and follow‐up), from 5316 patients, were analyzed. Clinical worsening occurred in only 14.5% (1908/13,160), whereas a reduction in headache frequency was observed in 56.8% of visit intervals (7475/13,160), with 34.8% of the intervals (4580/13,160) showing a reduction of 50% or greater. The change in headache frequency was minimal (increase in 0‐3 headaches/month) in 28.7% of intervals (3737/13,160). In the multivariable model, the odds of worsening were significantly higher with increasing age, female sex, chronic migraine, status migrainosus, depressive symptoms, higher PedMIDAS scores, and use of nutraceuticals, whereas the odds of worsening were lower for summer visits, caffeine drinkers, higher headache frequencies, and use of pharmaceuticals. Conclusions: The majority of pediatric patients who receive multimodal interdisciplinary care for migraine improve over time. Our findings highlight a set of clinical features that may help in identifying specific factors that may contribute to an unfavorable short‐term prognosis. [ABSTRACT FROM AUTHOR]

Objectives: To characterize a population of pediatric patients visiting an infusion center for acute migraine and determine predictors of first‐line treatment success in this population. Background: Though migraine is common in the pediatric emergency department and specialized infusion centers, little is known about this patient population and whether or not clinical data can be used to predict treatment response. Methods: This was an observational study involving a retrospective analysis of data from visits to the Cincinnati Children's Hospital infusion center for treatment of an acute migraine. Data were extracted from a database and chart reviews were completed for missing or outlying data. Descriptive statistics were used to outline patient: sex, age, race, primary ICHD‐III diagnosis, chronic migraine, medication overuse headache (MOH), headache frequency, month of treatment, headache severity, headache duration, use of acute medication at home in the past 24 hours and treatment received (metoclopramide vs prochlorperazine and dexamethasone vs no dexamethasone). The odds of success of first‐line intervention were modeled using simple logistic regression with the above characteristics used as predictors. Predictors with a P value <.05 in the multiple logistic regression model with progressive backwards selection were entered into a final multiple logistic regression model controlling for age, sex and diagnosis, where a P value <.05 was considered statistically significant. Results: Data from 837 visits (n = 837) were included in this analysis. Visits were significantly more frequent in the academic year as compared to the summer (Z = 10.716, P < .0001). In the multiple logistic regression model, the odds of first‐line treatment success decreased as headache frequency increased (OR = 0.951, 95% CI = 0.934‐0.969, P < .0001), were higher for patients without MOH (OR = 1.528, 95% CI = 1.097‐3.714, P = .0469), and were higher for patients who did not receive dexamethasone (OR = 1.528, 95% CI = 1.097‐3.714, P = .0469). Conclusions: Higher baseline headache frequency and presence of MOH may predict lower odds of treatment success after first‐line intervention for pediatric migraine in the acute setting. These predictors may be useful in stratifying patients for treatment protocols and for planning future intervention studies. [ABSTRACT FROM AUTHOR]

The article presents the discussion on red ear syndrome (RES) remaining a pathophysiologic mystery. Topics include reporting a child with isolated RES involving either or both ears and face treated successfully with indomethacin; and attempting further prevention having gabapentin, amitriptyline, and non-invasive vagus nerve stimulation.

Objective To translate, perform the cross-cultural adaptation, and an initial validation of the Brazilian Portuguese version of PedMIDAS (BP-PedMIDAS). Background Pediatric Migraine Disability Assessment (PedMIDAS) was developed to measure the impact of migraine among children and adolescents. Methods PedMIDAS was subjected to translation, back-translation, and application of the questionnaire to 40 children and adolescents with migraine for confirmation validation. Once validated, the psychometric properties were tested through administration to 100 children and adolescents with migraine. Results The mean time required to complete BP-PedMIDAS was 135 ± 51 seconds. BP-PedMIDAS had a Cronbach's coefficient α of 0.84 and a good stability (test-retest), with a good intraobserver and interobserver agreement (Pearson's correlation > 0.80) and correlated with the frequency of the headaches. These results mirrored those seen with PedMIDAS, further validating the interchangeability of the versions. Conclusion BP-PedMIDAS has been shown to be useful for assessing disability in children and adolescents. [ABSTRACT FROM AUTHOR]

The author reflects on the Childhood and Adolescent Migraine Prevention (CHAMP) study, a National Institutes of Health-funded trial that compared mitriptyline, topiramate and placebo in youth with migraines. Particular focus is given to the Pediatric Migraine Disability Assessment. Also mentioned are ethical issues raised by the study's placebo arm, response rate, and goal of the CHAMP trial.

The article highlights information about an application form regarding Pediatric Migraine Action Plan (PedMAP).

Objective To describe current patterns of use of nerve blocks and trigger point injections for treatment of pediatric headache. Background Peripheral nerve blocks are often used to treat headaches in adults and children, but the available studies and practice data from adult headache specialists have shown wide variability in diagnostic indications, sites injected, and medication(s) used. The purpose of this study was to describe current practice patterns in the use of nerve blocks and trigger point injections for pediatric headache disorders. Methods A survey was created in REDCap, and sent via email to the 82 members of the Pediatric and Adolescent Section of the American Headache Society in June 2015. The survey queried about current practice and use of nerve blocks, as well as respondents' opinions regarding gaps in the evidence for use of nerve blocks in this patient population. Results Forty-one complete, five incomplete, and three duplicate responses were submitted (response rate complete 50%). About 78% of the respondents identified their primary specialty as Child Neurology, and 51% were certified in headache medicine. Twenty-six (63%) respondents perform nerve blocks themselves, and seven (17%) refer patients to another provider for nerve blocks. Chronic migraine with status migrainosus was the most common indication for nerve blocks (82%), though occipital neuralgia (79%), status migrainosus (73%), chronic migraine without flare (70%), post-traumatic headache (70%), and new daily persistent headache (67%) were also common indications. The most commonly selected clinically meaningful response for status migrainosus was ≥50% reduction in severity, while for chronic migraine this was a ≥50% decrease in frequency at 4 weeks. Respondents inject the following locations: 100% inject the greater occipital nerve, 69% lesser occipital nerve, 50% supraorbital, 46% trigger point injections, 42% auriculotemporal, and 34% supratrochlear. All respondents used local anesthetic, while 12 (46%) also use corticosteroid (8 bupivacaine only, 4 each lidocaine + bupivacaine, lidocaine + corticosteroid, bupivacaine + corticosteroid, lidocaine + bupivacaine + corticosteroid, and 2 lidocaine only). Conclusion Despite limited evidence, nerve blocks are commonly used by pediatric headache specialists. There is considerable variability among clinicians as to injection site(s) and medication selection, indicating a substantial gap in the literature to guide practice, and supporting the need for further research in this area. [ABSTRACT FROM AUTHOR]

Objective The purpose of this investigation was to examine treatment adherence to medication and lifestyle recommendations among pediatric migraine patients using electronic monitoring systems. Background Nonadherence to medical treatment is a significant public health concern, and can result in poorer treatment outcomes, decreased cost-effectiveness of medical care, and increased morbidity. No studies have systematically examined adherence to medication and lifestyle recommendations in adolescents with migraine outside of a clinical trial. Methods Participants included 56 adolescents ages 11-17 who were presenting for clinical care. All were diagnosed with migraine with or without aura or chronic migraine and had at least 4 headache days per month. Medication adherence was objectively measured using electronic monitoring systems (Medication Event Monitoring Systems technology) and daily, prospective self-report via personal electronic devices. Adherence to lifestyle recommendations of regular exercise, eating, and fluid intake were also assessed using daily self-report on personal electronic devices. Results Electronic monitoring indicates that adolescents adhere to their medication 75% of the time, which was significantly higher than self-reported rates of medication adherence (64%). Use of electronic monitoring of medication detected rates of adherence that were significantly higher for participants taking once daily medication (85%) versus participants taking twice daily medication (59%). Average reported adherence to lifestyle recommendations of consistent noncaffeinated fluid intake (M = 5 cups per day) was below recommended levels of a minimum of 8 cups per day. Participants on average also reported skipping 1 meal per week despite recommendations of consistently eating three meals per day. Conclusions Results suggest that intervention focused on adherence to preventive treatments (such as medication) and lifestyle recommendations may provide more optimal outcomes for children and adolescents with migraine and their families. Once daily dosing of medication may be preferred to twice daily medication for increased medication adherence among children and adolescents. [ABSTRACT FROM AUTHOR]

Objective To describe baseline headache characteristics of children and adolescents participating in a multicenter, randomized, double-blinded, placebo-controlled, comparative effectiveness study of amitriptyline, topiramate, and placebo for the prevention of migraine (CHAMP Study). Methods Children and adolescents (age 8-17 years old, inclusive) diagnosed with migraine with or without aura, having headaches at least four times per month were enrolled from 2012 through 2014. The trial involved a baseline period (minimum of 28 days) during which prospective diaries were completed and demographics and headache features obtained. Results A total of 488 children and adolescents (mean age 14.0 ± 2.4 years) agreed to participate in the trial, with 361 randomized and 127 not randomized. Randomized subjects had a 5.5 ± 3.1 year history of headaches, with 15.1 ± 7.1 headache days per month (based upon retrospective report at screening visit). Prospective diaries reported 11.5 ± 6.1 headache days per 28 day baseline. Across this 28 day period, reported headache days per week were stable (about 3 headache days per week). Recording of individual headache features by diary (n = 4136 headache days) showed characteristics consistent with migraine (mean duration 10.5 ± 8.1 hours, mean severity 6.0 ± 2.1, 60% throbbing, 55% with activity worsening headaches, 55% with photophobia, and 47% with phonophobia). Conclusions Baseline data from the CHAMP Study suggested that the randomized sample was representative of the real world population of children and adolescents that present for treatment of migraine. Headaches in children and adolescents recorded during a 28 day prospective baseline period in this multi-site comparative effectiveness study did not change over the course of the baseline period, even though a clear diagnosis, recommendation for effective acute treatment, and standardized education about healthy habits occurred prior to the diary collection period. [ABSTRACT FROM AUTHOR]

Objective The objective of this secondary analysis of results from a previously published trial () in chronic migraine in children and adolescents was to examine if participants who received cognitive behavioral therapy and amitriptyline reached a greater level of reduction in headache frequency that no longer indicated a recommendation for preventive treatment as compared to those who received headache education and amitriptyline. Background Chronic migraine negatively affects children's home, school, and social activities. Preventive medication therapy is suggested for 5 or more headaches per month. Reduction to one headache day per week or less may suggest that preventive treatment is no longer indicated and provide a clinically relevant outcome for treatment efficacy and patient care. Methods Randomized study participants ( N = 135) kept a daily record of their headache frequency during 20 weeks of treatment and during a 1 year follow-up period. Baseline headache frequency was determined at the end of a 28 day screening period. Post treatment frequency was determined at 20 weeks ( N = 128 completed) and post treatment follow-up was measured 12 months later ( N = 124 completed). A chi-square test of independence was conducted by treatment group and by time point to determine group differences in the proportion of headache days experienced. Results At 20 weeks (post treatment), 47% of the cognitive behavioral therapy plus amitriptyline group had ≤4 headache days per month compared to 20% of the headache education plus amitriptyline group, ( P = .0011), and 32% of the cognitive behavioral therapy plus amitriptyline group had ≤3 headache days per month at 20 weeks compared to 16% of the headache education plus amitriptyline group, ( P = .0304). At the month 12 follow-up, 72% of the cognitive behavioral therapy plus amitriptyline group had ≤4 headache days per month compared to 52% of the headache education plus amitriptyline group, ( P = .0249), and 61% of the cognitive behavioral therapy plus amitriptyline group had ≤3 headache days per month at their month 12 follow-up compared to 40% of the headache education plus amitriptyline group, ( P = .0192). Conclusions Participants who received cognitive behavioral therapy and amitriptyline were more likely than participants who received headache education plus amitriptyline to reach the clinically meaningful outcome of less than or equal to 4 headache days per month at both time points. These results may help inform what treatment outcomes are possible for children and adolescents suffering from chronic migraine and provides further evidence for behavioral treatment to be considered as a key part of a first line treatment regimen. [ABSTRACT FROM AUTHOR]

Objective.--To evaluate factors that influence migraine recurrence after outpatient infusion or inpatient treatment for intractable migraine. Background.--Recurrence of migraine after acute treatment in an infusion center or an inpatient setting is not well documented in children and adolescents. Given the multifactorial pathogenesis of migraines, multiple factors may influence migraine recurrence. It has been reported that treatment with steroids may reduce the risk of migraine recurrence. The efficacy of steroids as a therapeutic adjunct has not been established. Studies in the adult population have yielded conflicting results. Methods.--This study is a retrospective chart review of patients presenting for treatment of an intractable migraine to the outpatient infusion unit or inpatient unit at Cincinnati Children's Hospital Medical Center (CCHMC). Data collected included: age, gender, location of treatment (outpatient, inpatient), migraine duration, diagnosis, severity, the addition of steroids to treatment protocols, and recurrence of migraine at 48 and 72 hours after discharge. Data were analyzed using Fisher's exact tests, logistic regression with backward elimination for variable selection, and least squares means slicing with associated odds ratios. Results.--Charts from 207 pediatric patients were analyzed. Using logistic regression analysis: location, gender, diagnosis, and age were all found to be significant predictors of migraine recurrence (P < .05). Patients treated in the inpatient setting were significantly less likely to experience recurrence compared to patients treated in an outpatient infusion unit (OR50.32; 95% CI 0.17-0.61, P5.0002). Male patients with a diagnosis of episodic migraine were significantly less likely to experience recurrence than male patients with chronic migraine (OR 0.17; 95% CI 0.04-0.73; P5.0074). The inclusion of steroids in this study population showed no significant reduction in migraine recurrence. The probability of recurrence decreased with age for episodic migraine patients, while the probability increased with age for chronic migraine patients. Conclusions.--Recurrence is an important consideration when treating intractable migraines. Age, gender, diagnosis, and location of treatment correlate with migraine recurrence, but the inclusion of steroids does not. Considering these factors in the management of migraines may improve the outcome of these patients and reduce the risk of recurrence. [ABSTRACT FROM AUTHOR]

A multi-centered, randomized, placebo-controlled, early intervention, cross-over study was conducted to evaluate the consistency of response of sumatriptan/naproxen sodium 85/500 mg ( S/ NS) over 4 attacks in the acute treatment of migraine in adolescents. Inclusion of subjects was dependent on their age of 12-17 years, frequency, and history of migraine headaches (1-8 per month) over the previous 6 months prior to screening and generally healthy males and females of non-childbearing potential that were not on excluded medications. Subjects were instructed to treat within 1 hour of pain onset, including when the pain was still mild. Subjects were randomized in a double-blind fashion using a computer-generated randomization list in which the study drug was prepared prior to study start, and subjects were allocated to a number in sequential order for each site. Each site was allocated number blocks in sets of 10 depending of the rate of enrollment. The objective of this study was to examine the efficacy of S/ NS vs placebo in the primary end-points of pain-free response at 2 hours (2h PF), 24-hour sustained pain-free response (24hPF), and pain-free response at 2 hours with early intervention (2h PFE) calculated as percentage out of all attacks. In the study, 94 subjects treated 347 attacks in total: treating 277 with S/ NS and 70 with placebo. Compared with placebo, S/ NS produced higher 2hPF rates ( S/ NS 37%, placebo 18%; P < .004), and 2h PFE with rates ( S/ NS 32%, 18% placebo; P < .03). Compared with placebo, 24h PF rates were S/ NS 86%, placebo 78%, P < .17, which were higher than placebo but not clinically significant. 2h PF was reported in at least 2 of the 3 migraines treated with S/ NS in 40.4% of subjects. 24h PF was reported in at least 2 of the 3 migraine treated with S/ NS in 86.2% subjects. Adverse reactions were generally low and comparable between S/ NS and placebo. [ABSTRACT FROM AUTHOR]

The authors reflect on the significance of a study of the neural mechanisms underlying cognitive behavioral therapy (CBT) in children and adolescents with migraine. Topics discussed include the recommendation of CBT with amitriptyline by the American Headache Society and American Academy of Neurology, factors that contribute to the reluctance patients and physicians to use CBT, and potential for CBT to be customized to individual patients.

Objective To review and critically evaluate the extant research literature pertaining to adherence in youth and adults with headache and to provide recommendations for future research. Background This article provides the first systematic review of pediatric headache adherence and updates a previous review of treatment adherence in adults with headache. Design Systematic review of empirical literature. Methods A literature search with no date restriction was conducted using Pub Med and Psyc INFO electronic databases and bibliographies of relevant articles. Results Adherence rates in adults with headache range considerably from 25% to 94% across treatment, assessment method, and definition of adherence utilized. Methods to assess adherence included retrospective prescription claims data, paper or electronic diaries, follow-up appointment attendance, written and verbal self-report of general adherence, verbal self-report of adherence over a specific amount of time via in person interview or telephone, validated adherence measures, adherence questionnaires without validation, and counselor ratings of homework. Each methodology and assessment tool demonstrated strengths and weaknesses. No studies have systematically examined medication adherence in children with headache, and the few available studies examining adherence to behavioral treatment have documented adherence rates ranging from 52% to 86%. Conclusions Adherence research in adults with headache is growing, but studies demonstrate a number of methodological shortcomings. Adherence research in children with headache, and adherence intervention research in both adults and children, is scant. Future research should use objective measures of adherence, consider over-the-counter medications and medication overuse, examine demographic, psychological, and behavioral correlates of adherence, assess adherence to botulinum toxin type A, and examine the efficacy of adherence interventions in individuals with headache. [ABSTRACT FROM AUTHOR]

The authors reflect on the updated standardized guidelines for the management of patients with headache disorders that was issued by the American Headache Society (AHS) as of April 2021. Other topics include the three levels of guidelines, namely, opinion pieces, evidence-based guidelines, and position statements/white papers, as well as AHS' collaboration with the American Academy of Neurology (AAN) in developing the guidelines.

Background Retrospective and cross-sectional studies have suggested a bidirectional relationship between migraine and mood disturbance. Objective The present prospective daily diary study examined the prevalence and temporal associations between migraine and daily mood, mood and next-day headache, and headache and next-day mood. Methods Sixty-nine children (50 females, 19 males) between the ages of 7 and 12 years and their parents attending neurology clinic appointments and having a diagnosis of migraine as defined by International Headache Classification 2nd edition criteria completed measures on the quality of life, headache disability, child emotions, and child behaviors. Children and parents then recorded children's headache occurrence, headache duration, headache severity, mood, daily hassles, and medication use on paper diaries once a day for 2 consecutive weeks. 'Mood' was defined using the Facial Affective Scale, which is a visual representation of negative and positive affect. Data were analyzed using multilevel models. Results Controlling for age, sex, quality of life, headache disability, and medication use, worse mood was associated with same-day occurrence, longer duration, and more severe headache in both child and parent report. Today's mood was not consistently associated with next-day headache, and today's headache was not associated with next-day mood in either child or parent report. Conclusions Results of this study lend support to a complex relationship between mood and headache in children with migraine. More research is needed to further elucidate the temporal nature of this relationship within a given day and over an extended period of time. [ABSTRACT FROM AUTHOR]

Background Migraine is one of the most common health problems for children and adolescents. If not successfully treated, it can impact patients and families with significant disability due to loss of school, work, and social function. When headaches become frequent, it is essential to try to prevent the headaches. For children and adolescents, this is guided by extrapolation from adult studies, a limited number of small studies in children and adolescents and practitioner preference. The aim of the Childhood and Adolescent Migraine Prevention ( CHAMP) study is to determine the most effective preventive agent to use in children and adolescents. Methods CHAMP is a double-blinded, placebo-controlled, multicenter, comparative effectiveness study of amitriptyline and topiramate for the prevention of episodic and chronic migraine, designed to mirror real-world practice, sponsored by the US National Institute of Neurological Disorders and Stroke/ National Institutes of Health ( U01NS076788). The study will recruit 675 subjects between the ages of 8 and 17 years old, inclusive, who have migraine with or without aura or chronic migraine as defined by the International Classification of Headache Disorders, 2nd Edition, with at least 4 headaches in the 28 days prior to randomization. The subjects will be randomized in a 2:2:1 (amitriptyline: topiramate: placebo) ratio. Doses are weight based and will be slowly titrated over an 8-week period to a target dose of 1 mg/kg of amitriptyline and 2 mg/kg of topiramate. The primary outcome will be a 50% reduction in headache frequency between the 28-day baseline and the final 28 days of treatment (weeks 20-24). Conclusions The goal of the CHAMP study is to obtain level 1 evidence for the effectiveness of amitriptyline and topiramate in the prevention of migraine in children and adolescents. If this study proves to be positive, it will provide information to the practicing physician as how to best prevent migraine in children and adolescents and subsequently improve the disability and outcomes. [ABSTRACT FROM AUTHOR]

Primary headache are one of the most common health complaints in children and adolescents, yet there remain significant gaps in our understanding of the underlying pathophysiology of these conditions. Recently, there have been several areas of research that have assisted with filling this gap in our knowledge. These areas include a better understanding of the disease characteristics including additional associated symptoms and the refinement of the description of related conditions and comorbidities; continued examination of the epidemiology of primary headaches; the progression of migraine across these developmental ages; the molecular and physiological changes; and the potential role for vitamins and cofactor deficiencies in the pathophysiology. These studies continue to add to our fund of knowledge on the basis of migraine and tension-type headache as primary neurological conditions and their impact on the developing brain. [ABSTRACT FROM AUTHOR]

Objectives.- To evaluate the long-term safety, tolerability, effectiveness, impact on quality of life, and medication satisfaction of sumatriptan/naproxen sodium in the acute treatment of migraine headache in adolescents. Methods.- This 12-month, multicenter, open-label, safety study was conducted in adolescents (aged 12-17 years) with an average of 2-8 migraines/month typically lasting >2 hours untreated for >6 months prior to initiation. Subjects were instructed to treat migraines as early as possible and were allowed to rescue 2 hours post dose with a single dose of a naproxen-containing product, over-the-counter pain reliever, or anti-emetics. Subjects were advised not to take a second tablet of sumatriptan/naproxen sodium without at least a 24-hour headache-free period. Safety evaluations included adverse events, laboratory tests, and vital signs and electrocardiogram evaluation. Other evaluations included freedom from pain, quality of life, and medication satisfaction. Results.- Of the 656 subjects enrolled, 622 (95%) treated at least 1 migraine with sumatriptan/naproxen sodium, of which 435 (70%) and 363 (58%) completed 6 and 12 months of the study, respectively. Overall, there were 12,927 exposures to sumatriptan/naproxen sodium: on average 2.5 tablets were taken per month per subject. The most common treatment-related adverse events were nausea (7%), dizziness (3%), muscle tightness (3%), and chest discomfort (3%). There were no deaths; 4 subjects had 5 serious adverse events (suicide attempt, hemolytic anemia and syncope, suicidal ideation, spontaneous abortion) unrelated to sumatriptan/naproxen sodium and resolved without sequelae. Seven percent of subjects discontinued participation in the study because of an adverse event; 5% of subjects discontinued due to lack of efficacy. Overall, 42% of the migraine attacks were pain-free within 2 hours of treatment with sumatriptan/naproxen sodium, subjects reported improvements from baseline in 2 of 3 quality of life domains over time, and were generally satisfied with the efficacy and overall treatment at the end of the study. Conclusion.- In adolescent migraineurs, after up to 12 months and over 12,000 exposures to sumatriptan/naproxen sodium, there were no new or clinically significant findings in the safety parameters, including the frequency and nature of adverse events, as compared to the individual components or to the adverse event profile in adults. In addition, sumatriptan/naproxen sodium provided freedom from pain over time, improvements in quality of life and medication satisfaction. [ABSTRACT FROM AUTHOR]

( Headache 2010;50:1005-1016) Objective.— To investigate the functional abnormalities of the motor cortices in children with migraine using magnetoencephalography (MEG) and a finger-tapping task. Background.— Cortical hyperexcitability has been reported in adults with migraine using MEG. Many children with migraine report difficulty with motor functioning. There is no report on motor-evoked magnetic activation in children with migraine using MEG and the latest signal processing methods. Methods.— Ten children with migraine (all female, 9 right-handed and 1 left-handed, aged 13-17 years) and 10 age- and gender-matched healthy children were studied with a 275-channel MEG system. After hearing a unilateral, randomly presented sound cue (500 Hz, 30 milliseconds square tone), each subject immediately performed a brisk index finger tapping with either the right or the left index finger. The auditory stimuli consisted of 200 trials of square tone, 100 trials per ear, randomly distributed. The latency and amplitude of neuromagnetic responses were analyzed with averaged waveforms. Neuromagnetic sources were estimated using synthetic aperture magnetometry (SAM). SAM images were normalized for each participant for group comparison. Results.— In comparison with healthy children, children with migraine had prolonged latency of motor-evoked magnetic response in the right hemispheres during left finger movement (62.33 ± 34.55 milliseconds vs 34.9 ± 17.29 milliseconds, P < .05). In addition, children with migraine had stronger activation in the motor cortex during right finger movement (8097.46 ± 5168.99 vs 4697.54 ± 3194.74, P < .05). Conclusions.— The results suggest that there are neurophysiological changes in the motor cortices of children with migraine that can be measured with neuromagnetic imaging techniques. The findings expand the ability to study the cerebral mechanisms of migraine using MEG and may facilitate the development of new therapeutic strategies in migraine treatment via alterations in cortical excitability. [ABSTRACT FROM AUTHOR]

Acute confusional migraine is a rare migraine variant primarily seen in childhood that lacks standardized diagnostic criteria. Acute symptomatic treatment for this disorder has not been established. We report 2 patients having a total of 6 episodes of acute confusional migraine where the symptoms resolved with prochlorperazine with variable success. Intravenous prochlorperazine was highly effective in 3 out of 4 episodes. [ABSTRACT FROM AUTHOR]

Objective.— To characterize menstrually associated headaches and migraine in adolescent girls and identify any developmental and pubertal changes. Background.— Headache and migraine is a common problem in adolescents with a transition to adult patterns. One pattern of adult migraine is the menstrual association in a significant number of women. Methods.— A retrospective analysis was performed of characteristics of adolescent's headaches including association with menstrual pattern. A detailed analysis of the patient- and parent-reported headache characteristics and patterns of longitudinal change with development and puberty was reviewed, including timing of headache with age and menstrual period and progression of these events over the adolescence. Results.— Of the 896 girls between 9 and 18 years old reviewed at initial evaluation, 331 (50.3% of menarchal girls and 36.9% of all girls) report experiencing headaches with their menstrual period. Of those reporting a menstrual pattern, 63.6% reported migraines starting between day −2 and +3 of their menstrual period start. Girls with menstrual migraine reported increased associated symptoms compared with girls without menstrual migraine. There was no difference in disability between girls with a menstrual pattern and those without a menstrual pattern ( t = 1.64; P = .10). Additionally, 160 girls reported a monthly pattern to their headaches prior to beginning menstruation, suggestive of a menstrually related migraine pattern prior to menstruation. Conclusions.— The pattern of menstrual association begins to become apparent during adolescence. Once the menstrual pattern has developed, this association is stable. Early identification of this pattern has potential long-term benefit for improved lifelong outcome. [ABSTRACT FROM AUTHOR]

Objective.— To examine the prevalence of obesity, the relationship between weight compared with headache frequency and disability, and effect of weight change on headache outcomes within a pediatric headache population. Background.— Headache and obesity are both common conditions in children and adults. Research in adults has suggested a relationship between the 2 conditions. This relationship has not yet been explored within a pediatric population. The effect of obesity and weight change on headache outcomes may have important implications for clinical care. Method.— Data on height, weight, age, and gender, as well as headache frequency and disability, were collected on 913 consecutive patients at 7 pediatric headache centers, the body mass index (BMI) calculated and the BMI percentile determined. The same data were collected on patients seen at 3- (n = 213) and 6-month (n = 174) follow-up for comparative analysis. Results.— The prevalence of overweight patients at initial visit did not significantly differ from the general pediatric population. BMI percentile was significantly correlated with headache frequency and disability at initial visit, although the correlations were relatively small. For children who were obese or at risk for overweight as initial visit, change in BMI was significantly positively correlated with change in headache frequency at 3- and 6-month follow-up. Conclusions.— Obesity is associated with headache frequency and disability in the pediatric headache population. For children who are overweight, weight loss can contribute to a reduction in headaches over time. Clinicians should consider child weight status in providing care for pediatric headache. [ABSTRACT FROM AUTHOR]

Objective.— To assess the effectiveness of aggressive therapy of status migraine in children and adolescents. Background.— Inpatient management of pediatric status migraine and intractable headache is limited because of a lack of studies and guidelines. Adult treatment is often based on anecdotal experience, although a few controlled studies have been reported. Added to that is the discomfort of general pediatricians and neurologists in using available effective treatments in pediatric patients (such as dihydroergotamine: DHE). Methods.— Charts of all patients admitted to the neurology service, at Cincinnati Children's Hospital Medical Center—Department of Neurology, for inpatient treatment for intractable headache/status migraine over a 6-week period were reviewed. Demographics, evaluation, diagnosis, and treatment used were tabulated. Data on the effectiveness of the treatments provided were evaluated. Thirty-two total consecutive charts were retrospectively reviewed during that period. Results.— Upon discharge, 74.4% of the patients were headache-free. The mean severity of the pain upon discharge was 1.02 ± 2.22 (using the 0-10 pain scale). Conclusion.— From our review, DHE is very effective in treating and aborting an episode of status migraine and should be offered to children and adolescent patients who have failed their usual abortive therapy to prevent further severe disability that mainly affects their schooling and social activities. [ABSTRACT FROM AUTHOR]

Objective.— To use a case–control design to evaluate the emotional and behavioral functioning of children with migraine. Background.— Research has indicated that children with migraine are at increased risk for emotional and behavioral problems such as depression and anxiety; however, methodological limitations in sample definitions, measurement strategies, and comparison groups remain problematic. Method.— Forty-seven participants diagnosed with migraine at a pediatric headache center participated in a home-based study of child functioning using standardized measures. Mothers and fathers of these children participated, as did control families recruited from among classmates. Results.— Indications of increased emotional and behavioral difficulties for children with migraine were found, primarily from the perspective of mothers. Exploratory analyses found several associations between mother and child perceptions of difficulties and persistence of headache symptoms following initiation of multidisciplinary headache treatment. Conclusions.— Continued concern regarding emotional well-being of children with migraine is warranted, but more work is needed to understand the differing perspectives of family members. Particular attention to emotional well-being is needed for children whose headache symptoms persist despite multidisciplinary treatment. [ABSTRACT FROM AUTHOR]

Objective.—The aim of the present study was to assess sleep patterns and the prevalence of sleep problems in adolescents with primary headaches using a validated sleep screening instrument, as well as to test the association between headache and pain features and adolescent sleep behaviors. Background.—Sleep disturbance is a common complaint that has long been associated with primary headaches, but there exists limited evidence of the headache-sleep relationship among teens. Methods.—Sixty-nine adolescents aged 13 to 17 years ( = 14.7; = 1.4) were evaluated for headaches at 2 pediatric neurology departments (90% migraine; 10% tension-type headache diagnoses). Participants completed the School Sleep Habits Questionnaire and a standardized questionnaire regarding headache characteristics. Results.—Sleep complaints were prevalent among adolescents with headaches including insufficient total sleep (65.7%), daytime sleepiness (23.3%), difficulty falling asleep (40.6%), and night wakings (38%). Statistically significant relationships between headache characteristics (eg, frequency, pain intensity) and teen sleep behaviors also emerged. Conclusions.—Our findings provide further support for an association between headache and sleep disturbances among adolescents with primary headaches. This information may provide further understanding of the nature and course of the patient's headache experience, as well as facilitate treatment planning to include recommendations for promoting good sleep hygiene. [ABSTRACT FROM AUTHOR]

Background.—Coenzyme Q10 (CoQ10) has been suggested to be effective in the prevention of migraine, and levels can be quantified with standardized reference ranges. Objective.—This study documents the prevalence of CoQ10 deficiency in migraine headache and examines the potential effectiveness of supplementation. Methods.—We assessed patients attending a tertiary care center with frequent headaches for CoQ10 deficiency. We recommended patients with low CoQ10 levels begin supplementation with CoQ10 as part of their multidisciplinary treatment plan. We assessed response to treatment including correction of CoQ10 deficiency, overall headache improvement, and headache disability. Results.—CoQ10 was measured in 1550 patients (mean age 13.3 ± 3.5, range 3 to 22 years). The mean total CoQ10 level was 0.60 ± 0.20 μg/mL (range 0.21 to 1.77 μg/mL). Of these patients, 32.9% were below the reference range. Patients with low CoQ10 were recommended to start 1 to 3 mg/kg per day of CoQ10 in liquid gel capsule formulation. In a subset of patients who returned for timely follow-up (mean, 97 days), the total CoQ10 level improved to 1.20 ± 0.59 μg/mL ( P < .0001), while the headache frequency improved from 19.2 ± 10.0 to 12.5 ± 10.8 ( P < .001) and headache disability assessed with PedMIDAS improved from 47.4 ± 50.6 to 22.8 ± 30.6 ( P < .001). Conclusions.—Deficiency of CoQ10 may be common in pediatric and adolescent migraine. Determination of deficiency and consequent supplementation may result in clinical improvement. Further analysis involving more scientifically rigorous methodology will be required to confirm this observation. [ABSTRACT FROM AUTHOR]

Headache can affect all aspects of a child's functioning, leading to negative affective states (eg, anxiety, depression, anger) and increased psychosocial problems (for instance, school absences, problematic social interactions). For children and adolescents who experience frequent headache problems, comorbid psychological issues are a well-recognized, but poorly understood, clinical phenomenon. The confusion surrounding the relationship between pediatric headache and psychopathology exists for several reasons. First, in some cases, headache has been inappropriately attributed to psychological or personality features based on anecdotal observations or interpretations that go beyond the available data. Additionally, measures of psychopathology have not always adhered to the American Psychiatric Association's diagnostic criteria, thus reducing the reliability of diagnostic judgments. Furthermore, the diagnosis of headache has not always followed standard criteria, and has been complicated by the emergence of new terms and evolving measures. Finally, methodological shortcomings, such as incomplete descriptions of the procedures and criteria used for the study, inadequate descriptions of headache severity, lack of a control group for comparison with individuals without headaches, reliance primarily on cross-sectional research designs that are often discussed with inferences to causal hypotheses, and the use of unstandardized assessment measures, have significantly limited the validity of research findings. The goal of the current review is to examine the extant literature to provide the most up-to-date picture on what the research has made available about the magnitude, specificity, and causes of psychopathology in children and adolescents with headache, in an effort to further elucidate their relationship and prompt a more methodologically rigorous study of these issues. [ABSTRACT FROM AUTHOR]

Objective.—To evaluate the sensitivity of the new International Classification of Headache Disorders-2nd edition (ICHD-II) criteria in the diagnosis of childhood migraine and to propose specific criteria for the diagnosis of childhood migraine. Background.—In 2004, ICHD-II was adopted by the International Headache Society. The prior version had been criticized for its lack of sensitivity in diagnosing childhood headaches. ICHD-II is felt to be an improvement as it provides for some differences between pediatric and adult migraine diagnosis in its footnotes, however, has yet to be validated. Clinically, it is the impression of many pediatric headache specialists that children's migraines are of shorter duration, tend to be bilateral rather than unilateral, and that children more often report either photophobia or phonophobia, rather than both. Methods.—The characteristics of headache in 260 patients, ages 18 and under, clinically diagnosed with migraine at two large pediatric headache centers were compiled using standard intake questionnaires. Inter-rater reliability in clinical diagnosis was determined by consensus of the clinical diagnosis. These data were analyzed applying the International Classification of Headache Disorders-1st edition (ICHD-I) and ICHD-II criteria for migraine to determine sensitivity of migraine diagnosis in comparison with clinical impression. Each headache characteristic in ICHD-II was analyzed individually to determine its effect on sensitivity of diagnosis. Results.—183/260 patients (70.4%) met ICHD-I criteria. 161/260 patients (61.9%) met the ICHD-II criteria with a 4- to 72-hour range. When the footnoted allowance of ICHD-II for short duration (2 hours) was utilized, 187/260 patients (71.9%) met criteria, while this improved to 192/260 patients (73.9%) with 1-hour duration. If duration was excluded, 210/260 patients (80.8%) met criteria. The most common reasons for patients not meeting the standard criteria were the requirement of unilateral location, headache duration and number of associated symptoms. Based on these observations, modified criteria were empirically derived and the sensitivity increased to 84.4%. Data were reanalyzed using the criteria of focal head pain, either bilateral or unilateral, shortened duration, and modified associated symptoms, which resulted in an improved sensitivity in migraine diagnosis of 84.4%. Conclusions.—Modification of ICHD-II criteria to include bilateral headache, headache duration of 1 to 72 hours, and nausea and/or vomiting plus two of five other associated symptoms (photophobia, phonophobia, difficulty thinking, lightheadedness, or fatigue), in addition to the usual description of moderate to severe pain of a throbbing or pulsating nature worsening or limiting physical activity, improved sensitivity of migraine diagnosis to 84.4%. [ABSTRACT FROM AUTHOR]

Objective.—To assess the long-term effectiveness and outcome of multidisciplinary treatment of childhood headaches 1, 2, and 5 years after initial treatment. Background.—Headaches are a common problem for children and adolescents and for many patients continue into adulthood. Outcome research for pediatric migraine headaches is limited, thus restricting knowledge of the effectiveness of long-term management and outcome. Methods.—Headache characteristics were assessed at the initial visit and were reevaluated 1, 2, and 5 years later in independent sub-groups of consecutive patients. These characteristics included headache frequency, severity, average duration, school absences, and overall perceived response to treatment. Results.—At 1 year, 96 patients were evaluated (mean age = 11.0 ± 3.4, 59% females), 69 patients at 2 years (mean age = 10.6 ± 3.4, 48% females), and 32 at 5 years (mean age = 10.5 ± 3.9, 66% females). The headaches were reported as better in 94% at 1 year, 85% at 2 years, and 94% at 5 years. The initial frequency was at 13.4 ± 10.8 headaches per month, 4.9 ± 7.0 at 1 year ( P < .001), 4.7 ± 7.6 at 2 years ( P < .001), and 4.5 ± 7.5 at 5 years ( P < .001). The severity decreased from 6.8 ± 1.8 to 5.1 ± 2.3 at 1 year ( P < .001), to 5.0 ± 2.4 at 2 years ( P < .001), and to 4.6 ± 2.5 at 5 years ( P < .01). The school days missed per month showed a marked decrease from 4.5 ± 9.5 at initial visit to 1.55 ± 2.8 at 5 years ( P < .001). Patients that were only seen at their initial visit and did not choose to return for follow-up had less frequent and shorter duration headaches on initial visit when compared with the rest of the sample and continued to be doing well at the 1-, 2-, and 5-year assessments. Conclusions.—Multidisciplinary treatment was found to be effective for children and adolescents with improvement of multiple outcome variants of pediatric migraine care, including frequency, severity, and school days missed. Patients who did not return to follow-up evaluation were more likely to have less frequent and shorter duration headaches at initial presentation. Regular follow-up care is needed for those children with more severe initial headache presentation. [ABSTRACT FROM AUTHOR]