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.

Multimodal Assessment of Medication Adherence Among Youth With Migraine: An Ancillary Study of the CHAMP Trial.

OBJECTIVE: Examine preventive medication adherence among youth with migraine. METHODS: Adherence (self-report, pill count, and blood serum drug levels) was assessed as an ancillary study that utilized data from 328 CHAMP Study participants (ages 8-17). CHAMP was a multisite trial of preventive medications. Participants completed a prospective headache diary during a six-month active treatment period during which youth took amitriptyline, topiramate, or placebo pill twice daily. Self-reported medication adherence was collected via daily diary. At monthly study visits, pill count measures were captured. At trial month 3 (trial midpoint) and 6 (end of active trial), blood serum drug levels were obtained. Self-report and pill count adherence percentages were calculated for the active trial period, at each monthly study visit, and in the days prior to participants' mid-trial blood draw. Percentages of nonzero drug levels were calculated to assess blood serum drug level data. Adherence measures were compared and assessed in context of several sociodemographic factors. Multiple regression analyses investigated medication adherence as a predictor of headache outcomes. RESULTS: Self-report and pill count adherence rates were high (over 90%) and sustained over the course of the trial period. Serum drug level adherence rates were somewhat lower and decreased significantly (from 84% to 76%) across the trial period [t (198) = 3.23, p = .001]. Adherence measures did not predict headache days at trial end; trial midpoint serum drug levels predicted headache-related disability. CONCLUSIONS: Youth with migraine can demonstrate and sustain relatively high levels of medication adherence over the course of a clinical trial.

Predictors of Improvement in Pediatric Chronic Migraine: Results from the Cognitive-Behavioral Therapy and Amitriptyline Trial.

Explore predictors of improvement in headache days and migraine-related disability through a secondary analysis of the cognitive-behavioral therapy plus amitriptyline trial in children and adolescents (Clinical Trials Registration Number: NCT00389038). Participants were 135 youth aged 10-17 years old diagnosed with chronic migraine. Predictor variables included group assignment (treatment or control), baseline scores from depression and quality of life measures, and demographic variables. Criterion variables included headache days and migraine-related disability. Higher baseline depression scores were indicative of more days with headache post-treatment regardless of group assignment. Family income at the higher-end of the low-income range was significantly associated with less migraine-related disability regardless of group assignment (Household Income: HINC-01 in The United States Census Bureau. Bureau, U, 2020). Results from this secondary analysis identify depression symptoms and family income as predictors that can impact headache frequency and migraine-related disability. Self-reported symptoms of depression and family income are important factors to consider as part of the biopsychosocial model of care.

Trajectory of treatment response in the child and adolescent migraine prevention (CHAMP) study: A randomized clinical trial.

OBJECTIVE: Identify preventive medication treatment response trajectories among youth participating in the Childhood and Adolescent Migraine Prevention study. METHODS: Data were evaluated from 328 youth (ages 8-17). Childhood and Adolescent Migraine Prevention study participants completed headache diaries during a 28-day baseline period and a 168-day active treatment period during which youth took amitriptyline, topiramate, or placebo. Daily headache occurrence trajectories were established across baseline and active treatment periods using longitudinal hierarchical linear modeling. We tested potential treatment group differences. We also compared final models to trajectory findings from a clinical trial of cognitive behavioral therapy plus amitriptyline for youth with chronic migraine to test for reproducibility. RESULTS: Daily headache occurrence showed stability across baseline. Active treatment models revealed decreases in headache frequency that were most notable early in the trial period. Baseline and active treatment models did not differ by treatment group and replicated trajectory cognitive behavioral therapy plus amitriptyline trial findings. CONCLUSIONS: Replicating headache frequency trajectories across clinical trials provides strong evidence that youth can improve quickly. Given no effect for medication, we need to better understand what drives this clinically meaningful improvement. Results also suggest an expected trajectory of treatment response for use in designing and determining endpoints for future clinical trials.Trial Registration. ClinicalTrials.gov Identifier: NCT01581281.

Prevalence of Headache Days and Disability 3 Years After Participation in the Childhood and Adolescent Migraine Prevention Medication Trial.

Importance: Migraine is a common neurological disease that often begins in childhood and continues into adulthood; approximately 6 million children and adolescents in the United States cope with migraine, and many frequently experience significant disability and multiple headache days per week. Although pharmacological preventive treatments have been shown to offer some benefit to youth with migraine, additional research is needed to understand whether and how these benefits are sustained. Objective: To survey clinical status of youth with migraine who participated in the 24-week Childhood and Adolescent Migraine Prevention (CHAMP) trial over a 3-year follow-up period. Design, Setting, and Participants: This survey study used internet-based surveys collected from youth ages 8 to 17 years at 3, 6, 12, 18, 24, and 36 months after completion of the CHAMP trial, which randomized participants to amitriptyline, topiramate, or placebo. At the end of the trial, the study drug was stopped, and participants received clinical care of their choice thereafter. The CHAMP trial was conducted between May 2012 and November 2015, and survey follow-up was conducted June 2013 to June 2018. Participants in this survey study were representative of those randomized in the trial. Data were analyzed from March 2020 to April 2021. Exposures: Survey completion. Main Outcomes and Measures: Headache days, disability (assessed using the Pediatric Migraine Disability Scale [PedMIDAS]), and self-report of ongoing use of prescription preventive medication. Results: A total of 205 youth (mean [SD] age, 14.2 [2.3] years; 139 [68%] girls; mean [SD] history of migraine, 5.7 [3.1] years) participated in the survey. Retention of participants was 189 participants (92%) at month 6, 182 participants (88%) at month 12, 163 participants (80%) at month 18, 165 participants (80%) at month 24, and 155 participants (76%) at month 36. Over the course of the 3-year follow-up, participants consistently maintained meaningful reductions in headache days (mean [SD] headache days per 28 days: CHAMP baseline, 11.1 [6.0] days; CHAMP completion, 5.0 [5.7] days; 3-year follow-up, 6.1 [6.1] days) and disability (mean [SD] score: CHAMP baseline, 40.9 [26.4]; CHAMP completion, 17.9 [22.1]; 3-year follow-up, 12.3 [20.0]). At 3 years after completion of the CHAMP trial, headache days were approximately 1.5 per week (changed from about 3 per week at trial baseline) and disability had improved from the moderate range to the low mild range on the PedMIDAS. Longitudinal analyses showed that amitriptyline and topiramate did not explain intercept random effects for either mean rate of headache days per week (amitriptyline: estimate [SE], 0.07 [0.05]; P = .16; topiramate: estimate [SE], 0.04 [0.05]; P = .50) or headache disability PedMIDAS total score (amitriptyline: estimate [SE], 0.25 [0.38]; P = .52; topiramate: estimate [SE], -0.09 [0.39]; P = .82) changes over time. Of 153 participants who reported on prescription drug use at 3 years, only 1 participant (1%) reported using prevention medication, and most participants reported no medication use at most time points. Conclusions and Relevance: These findings suggest that children and adolescents with longer than 5 years history of migraine who participated in the CHAMP trial may sustain positive clinical outcomes over time, even after discontinuing preventive pill-based treatment. This survey study could inform use and discontinuation timing of pharmacological preventive therapies for migraine in youth ages 8 to 17 years. Research is needed to examine mechanisms of treatment improvement and maintenance for preventive therapies, as well as placebo, in the pediatric population.

Correction to: Intravenous Migraine Treatment in Children and Adolescents.

The original publication of this article unfortunately contained the incorrect version of the manuscript. The original article has been corrected.

Clinic-based characterization of continuous headache in children and adolescents: Comparing youth with chronic migraine to those with new daily persistent headache.

OBJECTIVE: To describe the headache characteristics and functional disability of a large sample of treatment-seeking youth with continuous headache and compare these factors across diagnostic subgroups of chronic migraine and new daily persistent headache. METHODS: This retrospective study utilized clinical information (e.g. diagnosis, headache features, medication overuse, functional disability) from a large data repository of patients initially presenting to a multidisciplinary headache center with continuous headache. Patient inclusion in subgroup analyses for chronic migraine and new daily persistent headache was based on clinician diagnosis using International Classification of Headache Disorders (ICHD) criteria. RESULTS: The current sample included 1170 youth (mean age = 13.95 years, 78.8% female) with continuous headache. The overwhelming majority of these youth had headaches with migrainous features, regardless of their clinical diagnosis. Youth with chronic migraine reported a longer history of continuous headache symptoms and earlier age of headache onset than youth with new daily persistent headache and were more likely to have medication overuse. Most youth with continuous headache experienced severe migraine-related functional disability, regardless of diagnostic subgroup. CONCLUSIONS: Overall, youth with continuous chronic migraine and new daily persistent headache did not have clinically meaningful differences in headache features and associated disability. Findings suggest that chronic migraine and new daily persistent headache may be variants of the same underlying disease.

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.

Predictors of Short-Term Prognosis While in Pediatric Headache Care: An Observational Study.

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.

Paediatric migraine: evidence-based management and future directions.

Migraine is prevalent in children and adolescents and constitutes an important cause of disability in this population. Early, effective treatment of paediatric migraine is likely to result in improved outcomes. Findings from the past few years suggest that a biopsychosocial approach that uses interdisciplinary multimodal care is most effective for treatment of migraine in the paediatric population. Key elements of this management include effective and timely acute pharmacological interventions (such as NSAIDs and/or triptans), education of patients regarding self-management techniques, and psychological interventions such as biofeedback, relaxation and cognitive-behavioural therapy. The efficacy of current pharmacological or nutraceutical interventions for migraine prevention in children and adolescents is unclear, although reported placebo response patterns suggest that the effect of pill-taking behaviour is positive. As such, clinicians can consider adding a preventive intervention that involves a daily pill-taking behaviour to evidence-based non-pharmacological first-line preventive interventions (such as cognitive-behavioural therapy). More rigorous research is needed to delineate the role of pharmacological and nutraceutical interventions, the mechanisms of the clinically relevant placebo response, and interventions that enhance this response for migraine prevention in this population. Given the prevalence of migraine, cost-effective and efficacious strategies are needed for the large-scale delivery of interdisciplinary multimodal paediatric migraine care.

Predictors of First-Line Treatment Success in Children and Adolescents Visiting an Infusion Center for Acute Migraine.

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.

A pilot investigation of a mobile phone application and progressive reminder system to improve adherence to daily prevention treatment in adolescents and young adults with migraine.

BACKGROUND: Effective management of migraine requires adherence to treatment recommendations; however, adolescents with migraine take their daily medications only 75% of the time. Low-cost adherence-focused interventions using technology may improve adherence, but have not been investigated. METHODS: Thirty-five adolescents and young adults (13-21 years) with migraine participated in an AB-design pilot study to assess the use of a mobile phone adherence-promotion application ("app") and progressive reminder system. Adherence was calculated using electronic monitoring during the baseline period and medication adherence intervention. RESULTS: Relative to baseline, adherence significantly improved during the first month of the intervention. Specifically, improvements existed for older participants with lower baseline adherence. Self-reported app-based adherence rates were significantly lower than electronically monitored adherence rates. Participants rated the intervention as acceptable and easy to use. CONCLUSIONS: "Apps" have the potential to improve medication adherence and are a promising intervention for adolescents and young adults with low adherence. Involving parents in the intervention is also helpful. Providers should assess barriers to adherence and use of technology-based interventions, encourage parents to incorporate behavioral incentives, and provide referrals for more intensive interventions to improve long-term outcomes. Further, tracking adherence in an app may result in an underestimation of adherence. Future full-scale studies should be conducted to examine adherence promotion app interventions.

Ovarian hormones, age and pubertal development and their association with days of headache onset in girls with migraine: An observational cohort study.

Background Fifty-three percent of adolescent girls report headaches at the onset of menses, suggesting fluctuations of ovarian hormones trigger migraine during puberty. Aims To determine if urinary metabolites of estrogen and progesterone are associated with days of headache onset (HO) or severity in girls with migraine. Methods This was a pilot study and included 34 girls with migraine balanced across three age strata (pre-pubertal (8-11), pubertal (12-15), and post-pubertal (16-17) years of age). They collected daily urine samples and recorded the occurrence and severity of headache in a daily diary. Urine samples were assayed for estrone glucuronide (E1G) and pregnandiol glucuronide (PdG) and the daily change was calculated (ΔE1G, ΔPdG). Pubertal development was assessed by age, pubertal development score (PDS), and menstrual cycle variance. The primary outcome measures were HO days and headache severity. Generalized linear mixed models were used, and included the hormonal variables and three different representations of pubertal development as covariates. Results Models of HO days demonstrate a significant age*PdG interaction (OR 0.85 [95% CI 0.75, 0.97]) for a 1 standard deviation increase in PdG and three-year increase in age. A separate model showed a significant PDS*PdG interaction (OR -0.85 [95% CI; 0.76, 0.95]). ΔPDG was associated with headache severity in unadjusted models ( p < 0.017). Conclusion Age and pubertal development could moderate the effect of ovarian hormones on days of headache onset in girls with migraine.

Trajectory of Improvement in Children and Adolescents With Chronic Migraine: Results From the Cognitive-Behavioral Therapy and Amitriptyline Trial.

We compared headache frequency trajectories between clinical trial participants who received cognitive-behavioral therapy (CBT) and amitriptyline (CBT+A) or headache education (HE) and amitriptyline (HE+A) to determine if there was a differential time course of treatment response between the groups. One hundred thirty-five patients (age 10-17 years) diagnosed with chronic migraine participated, attending 8 one-hour one-on-one CBT or HE sessions with a trained psychologist for 8 weekly sessions, 2 sessions at weeks 12 and 16, and a post-treatment visit at week 20. Participants kept daily headache diaries and completed take-home assignments between visits. Data from daily headache diaries are presented for each day and according to 28-day periods. Trajectories of improvement indicate initial decrease in headache days began during the first month of treatment, for both groups, and continued to decrease throughout treatment. The CBT+A group had greater daily improvement than the HE+A group. A significantly greater proportion of the CBT+A group had a ≥50% reduction in headache days each month, and a significantly greater proportion of the CBT+A group had ≤4 headache days per month in months 3 through 5. Results indicate the trajectory of decrease in headache days is significantly better for patients receiving CBT+A versus HE+A. PERSPECTIVE: This article presents daily information about headache frequency over a 20-week clinical trial. Youth with chronic migraine who received CBT+A improved faster than those in the control group. Findings provide clinicians with evidence-based expectations for treatment response over time and ways of monitoring treatment success. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT00389038.

Treatment Adherence in Child and Adolescent Chronic Migraine Patients: Results From the Cognitive-Behavioral Therapy and Amitriptyline Trial.

OBJECTIVES: To examine treatment adherence among children and adolescents with chronic migraine who volunteered to be in a clinical trial using 3 measures: treatment session attendance, therapy homework completion, and preventive medication use by daily diary. MATERIALS AND METHODS: Analyses are secondary from a trial of 135 youth aged 10 to 17 years diagnosed with chronic migraine and with a Pediatric Migraine Disability Score over 20. Participants were randomly assigned to cognitive-behavioral therapy plus amitriptyline (CBT+A, N=64) or headache education plus amitriptyline (HE+A, N=71). Therapists recorded session attendance. Completion of homework/practice between sessions was reported to therapists by patients. Patients reported preventive medication adherence using a daily headache diary. RESULTS: Mean session attendance adherence out of 10 treatment sessions was 95% for CBT+A and 99% for HE+A. CBT+A participants reported completing a mean of 90% of home practice of CBT skills between the 10 sessions. Participants reported taking amitriptyline daily at a mean level of 90% when missing diaries were excluded and 79% when missing diaries were considered as missed doses of medication. DISCUSSION: Our findings demonstrate that youth with chronic migraine who agree to be a part of a clinical trial do quite well at attending therapy sessions, and report that they are adherent to completing home/practice between sessions and taking medication. These results lend further support to consideration of CBT+A as a first-line treatment for youth with chronic migraine and suggest that measurement of adherence when this treatment is provided in practice will be important.

Adherence to Biobehavioral Recommendations in Pediatric Migraine as Measured by Electronic Monitoring: The Adherence in Migraine (AIM) Study.

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.

Quantitative neuromagnetic signatures of aberrant cortical excitability in pediatric chronic migraine.

BACKGROUND: Reports have suggested that abnormal cortical excitability may be associated with acute migraines. The present study quantitatively assesses the degree of cortical excitability in chronic migraine as compared to acute migraine and healthy controls within the pediatric population. METHODS: We investigated 27 children suffering from chronic migraine, 27 children suffering from acute migraine, and 27 healthy controls using a magnetoencephalography (MEG) system, recording at a sampling rate of 6000 Hz. All groups were age-matched and gender-matched. Neuromagnetic brain activation was elicited by a finger-tapping motor task. The spatiotemporal and spectral signatures of MEG data within a 5-2884 Hz range were analyzed using Morlet wavelet transform and beamformer analyses. RESULTS: Compared with controls, the chronic migraine group showed (1) significantly prolonged latencies of movement-elicited magnetic fields (MEFs) between 5 and 100 Hz; (2) increased spectral power between 100 and 200 Hz, and between 2200 and 2800 Hz; and (3) a higher likelihood of neuromagnetic activation in the ipsilateral sensorimotor cortices, supplementary motor area, and occipital regions. Compared with acute migraine group, chronic migraine patients showed (1) significantly higher odds of having strong MEFs after 150 ms; and (2) significantly higher odds of having neuromagnetic activation from the deep brain areas. CONCLUSIONS: Results demonstrated that chronic migraine subjects were not only different from the healthy controls, but also different from acute migraine subjects. The chronification of migraines may be associated with elevated cortical excitability, delayed and spread neural response, as well as aberrant activation from deep brain areas.

Spatial Heterogeneity of Cortical Excitability in Migraine Revealed by Multifrequency Neuromagnetic Signals.

UNLABELLED: To investigate the spatial heterogeneity of cortical excitability in adolescents with migraine, magnetoencephalography (MEG) recordings at a sampling rate of 6,000 Hz were obtained from 35 adolescents with an acute migraine and 35 age- and sex-matched healthy control participants during an auditory-motor task. Neuromagnetic activation from low- to high-frequency ranges (5-1,000 Hz) was measured at sensor and source levels. The heterogeneity of cortical excitability was quantified within each functional modality (auditory vs motor) and hemispherical lateralization. MEG data showed that high-frequency, not low-frequency neuromagnetic signals, showed heterogeneous cortical activation in migraine subjects compared with control participants (P < .001). The alteration of the heterogeneity of cortical excitability in migraine subjects was independent of age and sex. The degree of the neuromagnetic heterogeneity of cortical activation was significantly correlated with headache frequency (r = .71, P < .005). The alteration of cortical excitability in migraine subjects was spatially heterogeneous and frequency dependent, which previously has not been reported. The finding may be critical for developing spatially targeted therapeutic strategies for normalizing cortical excitability with the purpose of reducing headache attacks. PERSPECTIVE: This article presents a new approach to quantitatively measure the spatial heterogeneity of cortical excitability in adolescents with migraine using MEG signals in a frequency range of 5 to 1,000 Hz. The characteristics of the location and degree of cortical excitability may be critical for spatially targeted treatment for migraine.

Cognitive Behavioral Therapy plus Amitriptyline for Children and Adolescents with Chronic Migraine Reduces Headache Days to ≤4 Per Month.

OBJECTIVE: The objective of this secondary analysis of results from a previously published trial (Clinical Trials Registration Number: NCT00389038) 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.