Eptinezumab for adolescents with chronic refractory headache: A retrospective chart review.

OBJECTIVE: To evaluate the safety and efficacy of eptinezumab for the treatment of chronic refractory headache in adolescents. BACKGROUND: Chronic refractory headache can lead to school absences and impaired quality of life in adolescents, and currently there are no pharmacologic treatments with level A evidence for headache prevention for this population. While observational data suggest that monoclonal antibodies to calcitonin gene-related peptide or its receptor may be helpful for adolescents who have refractory primary headache disorders, evidence is lacking for the use of eptinezumab. METHODS: This was a single-center, retrospective chart review. Demographic and headache phenotypic data were collected. Outcome measures included headache intensity and frequency pre- and post-infusion(s), and improvement in function or in associated symptoms. Adverse events were also collected. RESULTS: Nine patients with chronic migraine and two with new daily persistent headache received a first dose of 100 mg of eptinezumab. All of them had daily headache and nine had continuous headache at baseline. After the first infusion of 100 mg, two patients were no longer having daily headache, one patient stopped having continuous headache, and four patients noted headache intensity reduction. Additionally, one patient described a reduction in nausea and vomiting, and another patient noted improvement in function. Six patients received a second eptinezumab infusion of 100 mg, three had a third one, and one patient had four infusions of 100 mg. After the second infusion, one patient noted reduction in headache frequency, one experienced lower headache intensity, and two described pain "improving." With the third and fourth infusions, patients continued to report improvement in headache intensity. Subsequent infusions of 300 mg resulted in further reductions in headache frequency and intensity for some patients. Eptinezumab was overall well tolerated. CONCLUSION: While this was a small sample, findings suggest that eptinezumab may be a safe and effective treatment for chronic, refractory headache in adolescents.

Bridging the gap between preclinical scientists, clinical researchers, and clinicians: From animal research to clinical practice.

BACKGROUND: Collaborations amongst researchers and clinicians with complementary areas of expertise enhance knowledge for everyone and can lead to new discoveries. To facilitate these interactions, shared language and a general understanding of how colleagues in different subfields of headache and headache research approach their work are needed. METHODS: This narrative review focuses on research methods applied in animal studies, human studies including clinical trials, and provides an overview of clinical practice. RESULTS: For animal studies, we describe concepts needed to evaluate the quality and relevance of preclinical studies. For human research, fundamental concepts of neuroimaging, quantitative sensory testing, genetic and epidemiological research methods, and clinical research methodology that are commonly used in headache research are summarized. In addition, we provide an understanding of what guides headache clinicians, and summarize the practical approach to migraine management in adults and children. CONCLUSIONS: It is hoped that this review facilitates further dialogue between clinicians and researchers that will help guide future research efforts and implementation of research findings into clinical practice.

Melatonin for migraine prevention in children and adolescents: A randomized, double-blind, placebo-controlled trial after single-blind placebo lead-in.

BACKGROUND: Melatonin is effective for migraine prevention in adults. We hypothesized that melatonin would also be effective for migraine prevention in children and adolescents. METHODS: This was a randomized, double-blind trial of melatonin (3 mg or 6 mg) versus placebo for migraine prevention in 10-17 year-olds with 4-28/28 headache days at baseline. Participants were recruited from the UCSF Child & Adolescent Headache Program, UCSF child neurology clinic, and social media advertisements. Migraine diagnosis was confirmed by a headache specialist. Participants completed an 8-week single-blind placebo run-in. Those meeting randomization criteria (≥4 headache days and ≥23/28 electronic diary entries during weeks 5-8) were randomized 1:1:1 to placebo:melatonin 3 mg:melatonin 6 mg nightly for 8 weeks. The primary outcome measure was migraine days in weeks 5-8 of randomized treatment between melatonin (combined 6 mg + 3 mg) versus placebo. We aimed to enroll n = 210. RESULTS: The study closed early due to slow enrollment (n = 72). Two participants were in the single-blind phase when the study closed, therefore the meaningful n = 70. Sixteen percent (11/70) were lost to follow-up during the single-blind phase. An additional 21% (15/70) did not meet randomization criteria (<4 headache days: n = 5, <23/28 diary days: n = 7, both: n = 3). Sixty-three percent (44/70) were eligible to randomize, of whom 42 randomized (n = 14 per arm). Taking another preventive at enrollment (OR 8.3, 95% CI 1.01 to 68.9) was the only variable associated with meeting randomization criteria. Of those randomized, 91% (38/42) provided diary data in the final 4-weeks. However, given the amount of missing data, only those with ≥21/28 diary days were analyzed-7/14 (50%) in the placebo group, and 20/28 (71%) in the melatonin groups combined. Median (IQR) migraine/migrainous days in weeks 5-8 of double-blind treatment was 2 (1-7) in the placebo group versus 2 (1-12) in the melatonin groups combined; the difference in medians (95% CI for the difference) was 0 days (-9 to 3). There were no differences in adverse events between groups. CONCLUSIONS: When compared to recall at enrollment, headache days decreased across the single-blind placebo phase and the double-blind phase. There was no suggestion of superiority of melatonin; however, given the substantial portion of missing data, numerically higher in the placebo arm, and underpowering, this should not be interpreted as proof of inefficacy. Melatonin was generally well tolerated with no serious adverse events. Future migraine preventive trials in this age group may find this trial helpful for anticipating enrollment needs if using a single-blind placebo run-in. Enriching for those already on a migraine preventive may improve randomization rates in future trials, though would change the generalizability of results.

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.

Beyond pain control: Outcome and treatment preferences in pediatric migraine.

OBJECTIVE: The objective of this study was to describe treatment preferences and perceived quality of existing outcome measures among children and adolescents with migraine and their caregivers. BACKGROUND: Across disciplines, there is increasing recognition of the value of direct input from stakeholders. Little empirical work has been done to determine what outcomes matter most to pediatric patients with migraine and their caregivers. METHODS: In this qualitative study, we recruited participants from the multicenter, prospective Pediatric Migraine Registry. We used stratified purposive sampling to recruit children and adolescents of varied ages and headache frequency. Patients with migraine and their caregivers completed semistructured interviews targeting treatment preferences and perceived quality of existing outcome measures. Emergent themes and subthemes were identified using conventional content analysis. RESULTS: Thirty dyads of children/adolescents and their caregivers were enrolled and completed 59 interviews (n = 29 children/adolescent interviews and n = 30 caregiver interviews). Three themes emerged. (1) Symptom relief: Looking beyond headache resolution: Participants described the value of outcomes in addition to pain relief, including a reduction in migraine intensity and improvement in non-pain symptoms. (2) Trade-offs between side effects and relief: Participants described cost-benefit analyses that can occur with headache treatment and acknowledged the impact of drug side effects on daily life and medication adherence. (3) Child-centered treatment: Participants described medication attributes salient to the pediatric context, including age-appropriate routes of administration and adequate safety data. CONCLUSIONS: Children, adolescents, and caregivers impacted by migraine value outcomes in addition to traditionally studied migraine endpoints. Participants valued decreased pain severity, even in the absence of pain resolution. Participants also prioritized the absence of side effects and key medication attributes, including fast onset and age-appropriate routes of administration. These results highlight an opportunity to design patient-centered clinical trials, develop drugs, and support product labeling that align with the outcomes valued most by children and adolescents with migraine and their caregivers.

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

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

Benign paroxysmal torticollis: phenotype, natural history, and quality of life.

BACKGROUND: Benign paroxysmal torticollis (BPT) is characterized by attacks of head tilt associated with vomiting, irritability, and/or ataxia in early childhood. BPT is associated with migraine but risk factors are unknown. Impact on quality of life is also unknown. METHODS: Parents/caregivers of children with ongoing or resolved BPT participated in telephone interviews (n = 73). Those with ongoing BPT completed the Infant Toddler Quality of Life questionnaire (ITQoL). RESULTS: Median age of children at the time of interview was 2.9 years (range 0.25-23). BPT was ongoing in 52% (n = 38). Nineteen percent (n = 14) developed migraine (median age 9.25 years, range 2.5-23) and 63% (n = 46) developed another episodic syndrome associated with migraine. Proportion of patients who developed migraine was higher among those with certain migrainous symptoms during BPT attacks vs. those without: phonophobia (58 vs. 21%, p = 0.02), photophobia and phonophobia (55 vs. 23%, p = 0.05), and photophobia, phonophobia, and motion sensitivity (60 vs. 22%, p = 0.02). ITQoL results showed significant impact of BPT on quality of life. CONCLUSIONS: Children with BPT may develop migraine or other episodic syndromes associated with migraine. Presence of migrainous features during BPT episodes may increase likelihood of developing migraine. Though characterized as "benign," BPT can significantly impact children and families. IMPACT: Benign paroxysmal torticollis (BPT) is a rare condition of early childhood characterized by episodes of head tilt associated with vomiting, irritability, ataxia, pallor, and/or malaise. This cohort study describes the phenotypic spectrum of BPT, variable treatment, natural history and association with migraine, and impact on development and quality of life. Children with BPT may go on to develop migraine or episodic syndromes that may be associated with migraine; presence of migrainous features during attacks may increase odds of developing migraine. BPT can have significant impact on quality of life, demonstrated by findings from the Infant Toddler Quality of Life questionnaire.

Later high school start time is associated with lower migraine frequency in adolescents.

OBJECTIVE: To determine whether high school start time is associated with headache frequency in adolescents with migraine. BACKGROUND: Adolescence is marked by a physiologic delayed circadian phase, characterized by later bedtimes and wake times. The American Academy of Pediatrics (AAP) recommends that high schools start no earlier than 8:30 a.m., but most high schools in the United States start earlier. The study hypothesis was that adolescents with migraine whose high schools start at 8:30 a.m. or later (late group) would have lower headache frequency than those whose schools start earlier than 8:30 a.m. (early group). METHODS: This was a cross-sectional Internet survey study of US high schoolers with migraine recruited online through social media. Comparisons were made between the late group and the early group. The primary outcome measure was self-reported headache days/month. RESULTS: In total, 1012 respondents constituted the analytic set: n = 503 in the late group versus n = 509 in the early group. Mean (SD) self-reported headache days/month was 4.8 (4.6) versus 7.7 (6.1) in the late and early groups, respectively (p < 0.001); mean difference -2.9 (95% CI -2.2 to -3.6). Mean (SD) self-reported hours of sleep on a school night was 7.9 (0.9) versus 6.9 (1.3), p < 0.001. Adjusting for total hours of sleep, sex, taking a migraine preventive, days of acute medication use, hours of homework, grade level, and missing breakfast, mean (SD) self-reported headache days/month remained lower in the late group than in the early group: 5.8 (95% CI 5.3-6.2) versus 7.1 (95% CI 6.7-7.4), (p < 0.001); mean difference -1.3 (95% CI -1.9 to -0.7). CONCLUSION: Adolescents with migraine who attend high schools that follow AAP recommendations for start times have lower self-reported headache frequency than those whose high schools start before 8:30 a.m. If prospective studies confirm this finding, shifting to a later high school start time may be an effective strategy for migraine prevention in adolescents.

Newborn Daily Crying Time Duration.

PURPOSE: Current methods for estimating infant crying time are potentially subject to error as they rely on parents to contemporaneously log and calculate crying time. Our aim was to present the average daily infant crying times from a digital recording device, not dependent on parent-based measurement. DESIGN AND METHODS: We conducted a descriptive longitudinal survey of infant crying times. Parents of healthy, term newborns were provided with voice-activated digital recording devices and asked to record infants continuously for randomly selected 24-hour periods during a 4 week time period. We analyzed the daily crying time for infants at different weeks of life. RESULTS: Of 136 families approached, 28 (20.5%) families were consented with 3 families withdrawing and 5 families submitting incomplete datasets, leaving a total of 20 families with complete datasets. During the first week of life, the mean crying time was about 25 minutes/day, which remained stable for the next few weeks until five weeks of life, when mean crying time increased to almost 40 minutes/day with increasing variance. CONCLUSIONS: In our study sample, infant mean daily crying times based on objective data were much less than estimates in recent studies. PRACTICE IMPLICATIONS: This study suggests daily crying times measured by digital recorders are less than daily crying times based on parent diaries published in the literature. With the development of new 'apps' to record duration times, it may be clinically inappropriate to compare data based on digital recorders with norms from studies that use parent-reported crying times.

Lifestyle Advice for Pediatric Migraine: Blaming the Patient, or Evidence Based?

Children and teenagers with migraine are often advised to live a life of perfect balance-to sleep regularly and well, to eat breakfast each day, to drink plenty of water, and to exercise religiously. The logic is that doing so will decrease their migraine frequency. The corollary that follows is that failing to follow such advice will result in the patient continuing to experience migraine at its current frequency. This opens the door to potentially blaming the patients for their migraine and contributing to migraine stigma. This article reviews the current state of the evidence for each of these behavioral interventions for migraine prevention, and provides the clinician with practical advice for counseling patients.

Evidence Regarding Medication Overuse Headache in Children and Adolescents: Protocol for a Systematic Review.

OBJECTIVES: This proposed systematic review will identify the existing evidence on medication-overuse headache in children and adolescents. BACKGROUND: A number of medications have been shown to be effective for acute treatment of migraine in children and adolescents. However, patients may find they need to use their acute medications more frequently when migraine frequency is high. This has led to concern about their potential to develop medication-overuse headache. METHODS: We will search PubMed, Embase, Web of Science, PsycINFO, and Cochrane databases from their inception to present time. We will also search conference proceedings of the last 4 scientific meetings of relevant societies and scan the reference lists of studies identified through the search. Study designs will include case series, cross-sectional, cohort, case-control, and interventional studies. Participants will include children and adolescents under 18 years of age with primary headache disorders. We aim to determine whether frequency of acute medication use is associated with headache frequency in children and adolescents. Outcomes of interest include: (1) headache frequency; (2) change in headache frequency, with time and in relationship to use of acute medications; and (3) headache-related disability. We will also review data addressing treatment/management of medication overuse or medication-overuse headache in children and adolescents. Relevant comparators will be withdrawal vs reduction of acute medication, initiation of preventive therapy vs no initiation with or without withdrawal of acute medication, and initiation of preventive therapy early vs late. Outcomes of interest include (1) days of acute medication use; (2) headache frequency; (3) change in headache frequency; and (4) headache-related disability. After screening for inclusion, 2 team members will independently review and extract relevant data, and any discrepancies will be resolved through discussion and arbitration. We will assess risk of bias using appropriate tools (Cochrane Risk of Bias for randomized controlled trials (RCT) and Newcastle-Ottawa Score for observational studies). Data will be summarized descriptively in text and tables. RESULTS: This systematic review will provide an overview of the available evidence on medication-overuse headache in children and adolescents. CONCLUSIONS: Findings from this review will aid clinicians by clarifying for them the current state of the evidence base, and will inform design of future research on this topic.

Melatonin for Acute Treatment of Migraine in Children and Adolescents: A Pilot Randomized Trial.

OBJECTIVE: To determine what dose of melatonin is most effective for treating migraine acutely in children and adolescents. BACKGROUND: Acute migraine medications may not work for all patients and may cause side effects. Melatonin is effective for migraine prevention in adults and has been used acutely for procedural pain in children. Our goal was to determine whether a "high" or "low" dose of melatonin is more effective for treating migraine acutely in youth. METHODS: In this pilot, randomized, open-label, single-center, dose-finding trial, children and adolescents aged 4-17 years with episodic migraine were randomized to "high-dose" or "low-dose" dose melatonin (<40 kg: 4 mg vs. 1 mg; ≥40 kg: 8 mg vs. 2 mg). The primary outcome measure was change in mean pain score between time 0 and 2 hours. Secondary outcomes included 2-hour pain-relief and pain-freedom rates. RESULTS: Eighty-four participants (n = 42 per group) were enrolled in this study. Mean (SD) participant age was 11.8 (3.5) years and 55% (46/84) were female. Mean (SD) headache days/month was 5.6 (3.8). Sixty-six (79%) participants provided outcome data and were included in the analyses, n = 24 in the high-dose group and n = 22 in the low-dose group. The drop-out rate was 43% (18/42) in the high-dose group vs. 48% (20/42) in the low-dose group. Mean (SD) change in pain intensity at 2 hours was -2.7 (2.1) cm in the high-dose group vs. -2.3 (2.1) cm in the low-dose group (p = .581), a difference of 0.4 cm (95% CI: -1.17 to 1.92). Two-hour pain-freedom rate was 41% (7/17) vs. 27% (4/15) in the high-dose vs. low-dose groups (p = .415), and 2-hour pain-relief rate was 94% (16/17) vs. 80% (12/15), (p = .482). There were no serious adverse events. Napping occurred in the majority (67% (14/21) high dose vs. 47% (9/19) low dose). Higher mg/kg dose of melatonin and napping were each independently associated with greater headache benefit. CONCLUSIONS: As an acute treatment for pediatric migraine, both low and high doses of melatonin were associated with pain reduction; however, study drop-out was high. Higher dose and napping after treatment predicted greater benefit.

Development of a Prospective Real-World Data Clinical Registry of Children and Adolescents With Migraine.

OBJECTIVE: To develop a multicenter, multistakeholder, prospective clinical registry of children and adolescents with migraine to support the collection of real-world data of sufficient quality to support regulatory submissions and provide site-based infrastructure support for future clinical trials. BACKGROUND: As new migraine treatments come to market, pediatric efficacy and safety trials of these agents are needed. A clinical registry is an ideal regulatory strategy to provide both real-world data and site infrastructure to execute these trials. DESIGN: Multicenter, multistakeholder, prospective real-world data clinical registry of children and adolescents, 4-17 years of age, diagnosed with migraine with or without aura. Participants will be followed for up to 12 months at 3-month intervals, with interval recording of clinical data at study sites and self-reported data via mobile health application, as well as biobanking. We developed electronic case report forms that incorporated routinely collected clinical data with National Institute of Neurological Disorders and Stroke Headache Common Data Elements (Version 2.0). All data are captured in a 21 CFR Part 11 - compliant electronic data capture system - augmented by a real-time, web-based, and customizable data visualization platform. We engaged vendors to provide ancillary biobanking, patient data entry, and data visualization services. RESULTS: We used an iterative and highly collaborative multistakeholder approach to design and implement a streamlined registry protocol with input from all participating US sites. At each design and implementation step, we received input from therapeutic area experts, the US Food and Drug Administration (FDA), the National Institutes of Health, patient and parent advocates, health technology partners, drug developers, and site-based clinical investigators. The registry is governed by a multistakeholder steering committee with representation from sites, industry partners, patient advocates, and a member from the FDA (non-voting with respect to steering committee matters). The multistakeholder and site-driven approach to registry design and execution was highly efficient and resulted in the first patient enrolled within 6 months of concept development. CONCLUSIONS: By ensuring regulatory compliant implementation of the registry, we created both a source of real-world data and a multisite platform for the conduct of future clinical trials that can be submitted to regulatory authorities to support inclusion of pediatric data in approved drug labeling. A highly collaborative approach with broad stakeholder engagement at all stages of the registry development was a key to our operational success.

Assessing evidence-based medicine and opioid/barbiturate as first-line acute treatment of pediatric migraine and primary headache: A retrospective observational study of health systems data.

OBJECTIVES: To evaluate providers' use and predictors of evidence-based medicine or opioid/barbiturate as first-line acute treatment for children's initial presentation of acute migraine or primary headache. METHODS: This retrospective, observational study utilized patient (children ages 6-17) and provider/encounter characteristics extracted from the patient's Electronic Health Record from 2008-2014 during an initial encounter for migraine or primary headache. The primary outcome was provider evidence-based medicine utilization; overall prescriptions and opioid/barbiturate prescriptions were also evaluated. Hierarchical linear modeling examined whether Level 1 (patient: Demographic, insurance type) and Level 2 (provider/encounter: Treatment setting/location, encounter diagnoses) characteristics influenced outcomes. RESULTS: In all, 38,926 patients (56.7% female, mean age = 12.1) and 1617 providers were evaluated. Only 17.7% of patients were diagnosed with migraine; 16.1% received evidence-based medicine. Older children (OR = 1.07, p < 0.001), females (OR = 1.14, p < 0.001), and those diagnosed with migraine (OR = 4.71, p < 0.001) were more likely to receive evidence-based medicine. Among prescriptions, 15.8% were for opioids/barbiturates. Older children (OR = 1.14, p < 0.001) and those cared for in the emergency department/urgent care (OR = 2.02, p < 0.001) were at increased risk. CONCLUSIONS: Demographics and migraine diagnosis are associated with evidence-based medicine and opioid/barbiturates. Primary care provides an opportunity to target provider interventions to enhance effective pediatric headache treatment.

High School Start Time and Migraine Frequency in High School Students.

OBJECTIVE: To investigate whether later high school start time is associated with lower migraine frequency in high school students with migraine. BACKGROUND: Adequate sleep is thought to be important in managing adolescent migraine. The American Academy of Sleep Medicine recommends teenagers sleep ≥8 hours/night. Adolescents have a physiologically delayed sleep phase, going to bed, and waking later than children and adults. The American Academy of Pediatrics (AAP) accordingly recommends high schools start no earlier than 8:30 AM. METHODS: Cross-sectional observational study of U.S. high schoolers with migraine. Participants were recruited nationally using social media. Respondents attending high schools starting at 8:30 AM or later were compared to those attending earlier start time schools. The primary outcome was headache days/month. RESULTS: Two hundred and fifty-six subjects constituted the analysis set: 115 later group vs 141 earlier group. Age and sex did not differ. Mean (SD) self-reported headache days/month were 7 (5) vs 8 (7), respectively, (P = .985); mean difference (95% CI for the difference) was -0.8 (-2.3-0.7) days. Median (IQR) self-reported total hours of sleep/school night were: 5.6 (5.0-6.6) vs 5.6 (4.5-6.4), P = .058. Students attending later start time schools woke later (median [IQR] 6:38 AM [55 minutes] vs 6:09 AM [59 minutes], P < .0001) and left home later (median [IQR] 7:28 AM [28 minutes] vs 7:02 AM [60 minutes], P < .0001). Average commute time was also longer: 41 (21) minutes vs 28 (16), P < .0001. The vast majority in both groups reported missing breakfast at least once/week: 103/114 (90.4%) vs 128/141 (90.8%), P = .907. Hours of sleep did not correlate with headache days per month. CONCLUSION: High school start time does not have a large effect on headache frequency in high schoolers with migraine. Given the high variance in headache days/month observed in this study, a larger study would be needed to determine whether there might still be a small effect of starting high school at/after 8:30 AM. More research is needed to establish evidence-based recommendations about lifestyle factors in adolescent migraine management.

Preliminary Evidence that Melatonin Is not a Biomarker in Children and Adolescents With Episodic Migraine.

BACKGROUND: To date, there have not been reliable biomarkers to identify impending migraine episodes. A prior study in adults with migraine demonstrated a reduction in the urinary metabolic substrate of melatonin (urinary 6-sulfatoxymelatonin; aMT6s) during a migraine. The aim of this study was to examine whether evening urinary melatonin metabolite levels could predict migraine the next day in children and adolescents with migraine. METHODS: Twenty-one children and adolescents with migraine (aged 5-17 years) were recruited to this observational study conducted at UC San Francisco to provide urine samples for 10 days and maintain a prospective headache diary during the same period. Nightly melatonin metabolite 6-sulfatoxymelatonin in urine was assayed and results from nights preceding migraine were compared to nights preceding a non-headache day. RESULTS: Mean (±SD) aMT6s levels the night prior to a migraine attack were 56.2 ± 39.0 vs 55.4 ± 46.6 ng/mL (P = .915), and mean melatonin metabolite levels the night following migraine were 55.5 ± 46.9 vs 57.0 ± 37.7 ng/mL (P = .841). However, in post hoc exploratory analyses, aMT6s levels were lower the night before a migraine in those who experienced aura or premonitory symptoms. CONCLUSION: While urinary melatonin metabolites do not predict migraine attacks in children and adolescents overall, they may be predictive in those who experience premonitory phase symptoms as part of their migraine attacks.

The Association Between Parental Migraine and Infant Colic: A Cross-Sectional, Web-Based, U.S. Survey Study.

BACKGROUND: Infant colic, or excessive crying in an otherwise healthy infant, is common, although the cause(s) are not known. This study aimed to determine whether parental migraine is associated with infant colic. METHODS: This was a cross-sectional online survey study of biological parents of 4-8 week olds in the United States during February and March 2017 and October 2017-April 2018. Parents self-reported information about their and their infant's health using validated instruments wherever possible. Parents were recruited using social media advertisements and completed the survey online. Migraine was identified with a validated screener using modified International Classification of Headache Disorders 3rd edition criteria. Parental depression and anxiety were screened with the Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder Scale-2 (GAD-2). Parental seasonal allergies and asthma were assessed by self-report. Infant colic was determined based on parental response to the question, "Has your baby cried for at least 3 hours on at least 3 days in the last week?" RESULTS: A total of 1,715 surveys were completed over 2 recruitment periods; 1,419 formed the analysis set. Eight hundred twenty-seven were completed by biological mothers and 592 by biological fathers. Mean (SD) maternal age: 28.9 (5.1) years; 33.5% had migraine/probable migraine. Maternal migraine was associated with increased odds of infant colic: OR 1.7 (1.3-2.4). Among mothers with migraine, headache frequency ≥15 days/month was associated with higher risk of infant colic (OR 2.5 (1.2-5.3)); and anxiety was borderline associated (OR 1.7 (1.0-2.9)). Mean (SD) paternal age was 31.6 (4.5) years; 20.8% had migraine/probable migraine. Paternal migraine was not associated with infant colic: OR 1.0 (0.7-1.5). Fathers with depression (OR 2.4 (1.4-4.3)) or anxiety (OR 1.7 (1.1-2.7)) were more likely to have a baby with colic but having a girl infant was protective: (OR 0.7 (0.5-0.97)). CONCLUSIONS: Mothers with migraine are more likely to have a baby with colic, while fathers with migraine are not. Further research is needed to determine the mechanisms underlying these findings. In the meantime, clinicians may wish to counsel parents with a maternal history of migraine about the increased possibility of having a colicky infant and provide resources and education about infant crying.