Remote electrical neuromodulation (REN) wearable device for adolescents with migraine: a real-world study of high-frequency abortive treatment suggests preventive effects.

Introduction: Migraine is a chronic neurological disease manifesting as attacks of disabling head pain and associated symptoms. Remote electrical neuromodulation (REN) is a non-pharmacological, prescribed, wearable device (Nerivio®). This device has been certified by the FDA for the acute and/or preventive treatment of migraine with or without aura in patients 12 years of age or older. The device is affixed to the user's arm during 45-min treatment sessions and is operated using a smartphone app. This study (NCT05769322) aims to evaluate whether frequent use of REN for the acute treatment of migraine in adolescents resulted in a reduction in monthly migraine treatment days (MMTD), as previously demonstrated in adults through a dedicated prevention clinical trial (NCT04828707). Methods: The study included real-world prospective data from adolescent patients who used REN on at least 10 days every 28-day month, following the REN migraine prevention guideline of an every-other-day pattern. Additional requirements were at least three REN treatment days in each of the two subsequent months. The number of MMTD was used as a proxy measure for the number of monthly migraine days (MMD). The change in MMTD from the first month, taken as a "baseline," to each of the following months was used to evaluate the presence and size of potential migraine preventive benefits of REN in adolescents. Results: A total of 83 adolescents were eligible for analysis. The users were 15.9 ± 1.3 years of age (mean ± SD), and 89% of them were female. The results demonstrated a substantial month-to-month reduction in the mean (±SD) number of REN treatment days from 12.6 (±3.2) MMTD in the first month to 9.0 (±4.8) MMTD in the second month (p < 0.001), and a further decrease to 7.4 (±4.2) MMTD in the third month (p < 0.001). This indicates an accumulative reduction of 5.2 (±4.8) mean REN MMTD from the first month to the third month of consecutive REN treatment. The users also reported consistent 2-h acute pain responses in at least 50% of their treated attacks, with 61.9% of the users reported experiencing pain relief, 24.5% reported pain freedom, 67.4% indicated relief in functional disability, and 41.3% reported complete freedom from functional disability. Conclusion: The frequent use of REN among adolescents as an acute treatment for migraine attacks resulted in a decrease in the mean number of monthly treatment days in the subsequent months, suggesting that REN may have potential preventive benefits for migraine in this subpopulation.

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.

Headache in the Pediatric Population: Focus on Migraine.

Pediatric headache is a common condition with significant impact on quality of life and ability to function in academic, social, and extracurricular activities. Most pediatric patients seen in primary care and neurology clinics with headache have primary headache disorders. Diagnosis is largely based on clinical history. Imaging is rarely needed in the absence of red flag features. Careful diagnosis is important to guide appropriate treatment. Treatment focuses on a biopsychosocial model integrating lifestyle, pharmacologic and nonpharmacologic treatment modalities. As few therapies are approved in the pediatric population, treatments are often used off-label based on evidence extrapolated from adult studies. Outcomes vary over time but are generally favorable when headache disorders are diagnosed promptly and managed in a multidisciplinary setting.

Acute and chronic management of posttraumatic headache in children: A systematic review.

OBJECTIVES: The goal of this paper is to provide a compilation of the evidence for the treatment of posttraumatic headache (PTH) in the pediatric population. Headache features and timing of therapy were considered. BACKGROUND: Headache is the most common symptom following mild traumatic brain injury (mTBI), affecting more than 80% of children and adolescents. It is unclear whether treatment for PTH should be tailored based on headache characteristics, particularly the presence of migraine features, and/or chronicity of the headache. METHODS: Systematic literature searches of PubMed, Embase, Scopus, and Cochrane databases (1985-2021, limited to English) were performed, and key characteristics of included studies were entered into RedCAP® (Prospero ID CRD42020198703). Articles and conference abstracts that described randomized controlled trials (RCTs), cohort studies, retrospective analyses, and case series were included. Participants included youth under 18 years of age with acute (<3 months) and persistent (≥3 months) PTH. Studies that commented on headache improvement in response to therapy were included. RESULTS: Twenty-seven unique studies met criteria for inclusion describing abortive pharmacologic therapies (9), preventative pharmacotherapies (5), neuromodulation (1), procedures (5), physical therapy and exercise (6), and behavioral therapy (2). Five RCTs were identified. Studies that focused on abortive pharmacotherapies were completed in the first 2 weeks post-mTBI, whereas other treatment modalities focused on outcomes 1 month to over 1-year post-injury. Few studies reported on migrainous features (7), personal history of migraine (7), or family history of migraine (3). CONCLUSIONS: There is limited evidence on the timing and types of therapies that are effective for treating PTH in the pediatric population. Prospective studies that account for headache characteristics and thoughtfully address the timing of therapies and outcome measurement are needed.

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.

Calcitonin Gene-Related Peptide Monoclonal Antibody Use for the Preventive Treatment of Refractory Headache Disorders in Adolescents.

BACKGROUND: Monoclonal antibodies to calcitonin gene-related peptide or its receptor have clinical trial evidence in adults with headache, but data are lacking in adolescents. The objective of this study was to describe the safety and efficacy of calcitonin gene-related peptide monoclonal antibody treatment in adolescents with chronic headache disorders. METHODS: We performed a retrospective multisite cohort study of patients less than 18 years of age who received a calcitonin gene-related peptide monoclonal antibody for headache prevention. Demographics, baseline headache characteristics, efficacy, and side effect data were collected. RESULTS: The study population comprised 112 adolescents who received at least one dose of a calcitonin gene-related peptide monoclonal antibody. Mean (S.D.; range) age at first dose was 15.9 years (1.4; 10.3 to 17.8). Ninety-four patients (83.9%) had chronic migraine, 12 (10.7%) had new daily persistent headache, and six (5.4%) had persistent post-traumatic headache. At baseline, the mean (S.D.) number of headache days per month was 26.9 (6.1) (n = 109) and headache was continuous in 75 of 111 (67.6%). At first follow-up visit there was a significant reduction in headache frequency compared with baseline (-2.0 days; 95% confidence interval, -0.8 to -3.2). Significant benefit was perceived by 29.5% of patients at first follow-up visit (n = 33/112) and 30.1% (n = 22/73) at second follow-up visit. A significant functional improvement was perceived by 31% of patients (n = 31/94) at the first follow-up visit and 22.4% (n = 15/67) at the second follow-up visit. The most common side effects were injection site reactions in 17.0% (n = 19) and constipation in 8.0% (n = 9). Five patients (4.5%) discontinued because of side effects. CONCLUSIONS: Side effects with calcitonin gene-related peptide monoclonal antibody treatment in adolescents were similar to those reported in adult trials. Calcitonin gene-related peptide monoclonal antibody treatment appears to benefit a proportion of adolescents with chronic refractory headache disorders.

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.

Pediatric Post-Traumatic Headache and Implications for Return to Sport: A Narrative Review.

BACKGROUND: Headache attributed to mild traumatic injury of the head (aka: mild traumatic brain injury, mTBI), frequently abbreviated to Post-Traumatic Headache (PTH), is one of the most common and disabling symptoms after a head injury. PTH often phenotypes to migraine. Evidence for treating PTH in the pediatric population is limited. Widely accepted guidelines do not exist to aid the clinician and there are currently no placebo-controlled trials for the pharmacologic management of PTH in this age group. Recommendations for when to return a child or adolescent to sport if they develop and/or are being treated for persistent PTH (PPTH) are lacking. The objective of this narrative review is to review the implications of returning an adolescent with PPTH to sport. METHODS: Pediatric neurologists with special qualification in headache collaborated on this narrative review. Literature was searched up until Oct 2019 for articles pertaining to PTH, concussion, mTBI, and the return of a pediatric athlete to sport after mTBI. Article inclusion was at the discretion of the authors. There was author consensus regarding all recommendations made. CONCLUSION: The authors recommend that strict adherence to the guidelines that return to sport cannot occur until a child is symptom free at rest, off any medication, may be unreasonable in certain situations. Symptom stability is the proposed new concept for return to sport.

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.

Pediatric Migraine: An Update.

This article outlines key features of diagnosis and treatment of migraine in children and adolescents. It emphasizes techniques that can be used by clinicians to optimize history taking in this population, as well as recognition of episodic conditions that may be associated with migraine and present in childhood. Acute treatment strategies include use of over-the-counter analgesics and triptan medications that have been approved by the US Food and Drug Administration for use in children and adolescents. Preventive treatment approach includes lifestyle modifications, behavioral strategies, and consideration of preventive medications with the lowest side effect profiles.

Occipital Headaches and Neuroimaging in Children.

PURPOSE OF REVIEW: The goal of this review is to outline the prevalence and significance of occipital headaches in children and how they relate to neuroimaging findings. We seek to evaluate the concern that occipital headaches in children are indicative of secondary headache pathology by reviewing the yield of neuroimaging in pediatric patients with occipital headache location. RECENT FINDINGS: Occipital headaches are a common presentation of primary headache disorders in children, seen in 7-16% of children presenting for evaluation of headache and in up to 20% of children diagnosed with migraine in the emergency department. Review of recent literature confirms that in and of itself, occipital location of headache in a child with recurrent headache and a normal physical examination should not be regarded as worrisome. Headaches with associated signs on neurologic examination should be investigated for a secondary cause, regardless of headache location. Occipital headaches that do not meet criteria for a primary headache disorder should be evaluated for site-specific occipital headache conditions. Neuroimaging for recurrent headache in children who have normal neurological examinations has an overall low yield (0-4.1%) for actionable findings in recent studies. Importantly, an abnormal neurologic examination often predicts the presence of neuroimaging abnormalities. In the absence of an atypical history or abnormalities on clinical examination, occipital headaches in children are no more likely to be associated with intracranial pathology than headaches in other locations. If the child's headaches are otherwise consistent with migraine or another primary headache disorder, and the neurologic examination is normal, the yield of neuroimaging is low, and imaging can generally be deferred.

Transcranial Magnetic Stimulation for Migraine Prevention in Adolescents: A Pilot Open-Label Study.

OBJECTIVE: To assess the feasibility, tolerability, and patient acceptability of single-pulse transcranial magnetic stimulation (sTMS) for migraine prevention in adolescents in an open-label pilot study. BACKGROUND: Migraine is common in adolescents and can be disabling. Well tolerated preventative therapies that are safe and effective are needed. METHODS: This was an open-label prospective pilot feasibility study of sTMS for migraine prevention in adolescents aged 12-17 years. Participants used sTMS twice daily in a preventative fashion, as well as additional pulses as needed acutely. A 4-week baseline run-in period (weeks 1-4) was followed by a 12-week treatment period. Feasibility was the primary outcome. Secondary outcomes included tolerability and acceptability, as well as the change in headache days, number of moderate/severe headache days, days of acute medication use, and PedMIDAS (headache disability) scores between the run-in period (weeks 1-4) and the third month of treatment (weeks 13-16). RESULTS: Twenty-one participants enrolled. Nineteen completed the baseline run-in, and 12 completed the study. Using sTMS proved feasible and acceptable with overall high compliance once treatment administration was streamlined. Initially, for preventive treatment, participants were asked to give 2 pulses, wait 15 minutes, then give 2 additional pulses twice daily. This 15-minute delay proved challenging for adolescents, particularly on school days, and therefore was dropped. Study completion rate went from 4/13 (31%) to 7/8 (88%) once this change was made, P = .024. On average, participants used the device preventively between 22 and 24 days over a 28-day block. There were no serious adverse events. Two participants reported mild discomfort with device use. CONCLUSION: sTMS appears to be a feasible, well-tolerated, and acceptable nonpharmacologic preventive treatment for migraine in adolescents. In designing future trials of sTMS for migraine prevention in adolescents, streamlined treatment administration will be essential to minimize drop-out. Efficacy needs to be assessed in a larger trial.