Sleep Disorders and Chronic Pain Syndromes in the Pediatric Population.

Sleep problems are widespread in children and adolescents suffering from chronic pain disorders. Sleep loss intensifies the experience of pain and is detrimental to the budding self-efficacy of a young individual with limitless horizons. Addressing sleep disorders may prevent the chronification of pain and prevent adverse health outcomes, such as functional impairment, psychiatric comorbidities and overall poor quality of life. This review will explore the cyclical nature between sleep, pain and mood, as well as the functional impact of this relationship on children and adolescents. There will be a discussion about sleep assessment and diagnostic testing, followed by a description of sleep disturbances found in specific pain conditions, ranging from headache, musculoskeletal/abdominal pain, to rheumatologic disorders. Finally, there will be a brief review of pharmacologic and behavioral interventions designed to improve sleep quality, and when possible, to alleviate pain.

Preliminary exploration of a multidimensional sleep health composite in adolescent females with frequent migraine.

OBJECTIVE: This observational study aimed to: (i) describe and explore preliminary psychometric properties of a multidimensional sleep health composite score in adolescent females with frequent migraine; and (ii) examine associations between the composite score, headache characteristics, and emotional health. BACKGROUND: Sleep health is a multidimensional construct comprised of various dimensions of sleep and circadian functioning, including Regularity, Satisfaction, Alertness, Timing, Efficiency, and Duration (Ru-SATED framework). The Ru-SATED sleep health composite score may provide a holistic perspective of sleep among adolescents with frequent migraine in the context of neurobiological and psychosocial impacts on sleep unique to this developmental period. METHODS: In all, 60 female adolescents (aged 12-18 years) with high-frequency episodic or chronic migraine completed wrist-worn actigraphy for 10 days and concurrent daily electronic surveys assessing headache, sleep, and emotional health. A sleep health composite score was derived from empirically supported "healthy" versus "unhealthy" ratings on the six Ru-SATED sleep dimensions. RESULTS: Half of participants (27/54 [50%]) had a composite score ≥4 (i.e., at least four of the six dimensions rated as poor). Convergent validity of the composite score was acceptable (rs = 0.30-0.56, all p < 0.05). Internal consistency among the dimensions was low (α = 0.45). Multivariate multiple regression models indicated that worse sleep health was associated with greater headache-related disability (B = 0.71, p = 0.018) and anxiety (B = 0.59, p = 0.010), and trended toward significance for sadness (B = 0.35, p = 0.052). The composite score was not significantly associated with headache frequency or severity. CONCLUSIONS: A multidimensional sleep health composite score may provide an alternative, more comprehensive picture of sleep disturbance among adolescent females with frequent migraine. Larger studies are needed to examine psychometric properties more rigorously and further explore the composite score as a potentially unique predictor of headache outcomes.

Efficacy of IV Valproic Acid and Oral Valproic Acid Tapers for the Treatment of Pediatric Headaches in the Emergency Department.

Background and Objectives: Pediatric headaches, including migraine, are a common reason for emergency department (ED) presentation. IV valproic acid (VPA) followed by oral VPA tapers are often used to abort pediatric headache and reduce recurrence, though limited data exist regarding this approach. This study evaluated the effectiveness of IV VPA and oral VPA tapers for the treatment of acute pediatric headaches in the ED in preventing return encounters. Methods: This is a retrospective cohort study of patients aged 5-21 years presenting to a tertiary-care pediatric ED from 2010 to 2016 who received IV VPA for headache or migraine. Primary outcomes were ED disposition, percent pain reduction (initial vs 2-hour patient-reported pain score [10-point scale]), and return for acute headache treatment within 1 month. Results: A total of 486 ED encounters were included with a median patient age of 15 years; most of them were females (76%, 369/486). Of available pain scores within 2 hours of IV VPA administration, 41% (173/425) had ≥50% pain reduction. Fifty-two percent (254/486) were discharged without additional treatment, 14% (69/486) were discharged after additional treatment, and 33% (163/486) were admitted to the hospital. Initial pain score, number of preceding home treatments, and number of preceding ED treatments were not associated with ED disposition. Oral VPA tapers were prescribed in 39% (94/253) of encounters when the patient was discharged after IV VPA. Oral VPA tapers produced a transient decrease in recurrence at 72 hours, which was no longer present at 1 week nor 1 month. There was no difference in the time to recurrence or total number of return visits within 1 month. Discussion: IV VPA was efficacious in treating pediatric headaches evaluated in the ED, with nearly two-thirds of patients discharged home after administration. Oral VPA tapers did not reduce total headache recurrence nor time to recurrence. Given the limited benefit of oral VPA tapers, this practice should be re-examined. Classification of Evidence: This study provides Class IV evidence that for children with headache seen in the ED, IV VPA reduces head pain and Class III evidence that following this with an oral VPA taper is of no benefit.

Dots and spots: A retrospective review of T2-hyperintense white matter lesions in pediatric patients with and without headache.

OBJECTIVE: We aimed to determine if T2-weighted hyperintense white matter lesions (WMLs) on brain magnetic resonance imaging (MRI) occur more frequently in pediatric patients with migraine and other primary headache disorders compared to the general pediatric population. BACKGROUND: Small foci of T2 hyperintensity in the white matter are frequently identified on brain MRI during the workup of pediatric headache. Such lesions have been reported to be more common among adults with migraine versus adults without migraine; however, this association has not been well established in the pediatric population. METHODS: We performed a retrospective cross-sectional single-center study of electronic medical records and radiologic studies, examining pediatric patients from 3 to 18 years old who underwent brain MRI between 2016 and 2021. Patients with existing intracranial disease or abnormalities were excluded. Patients with reports of headache were categorized. Imaging was reviewed to determine the number and location of WMLs. Headache-associated disability scores (Pediatric Migraine Disability Assessment) were noted, when available. RESULTS: Brain MRI of 248 patients with a diagnosis of headache (144 with migraine, 42 with non-migraine primary headache, and 62 with headache that could not be further classified) and 490 controls were reviewed. WMLs were encountered commonly among all study participants, with a prevalence of 40.5% (17/42) to 54.1% (265/490). There was no statistically significant difference comparing the number of lesions between each of the headache groups and the control group: migraine group versus control group median [interquartile range (IQR)], 0 [0-3] versus 1 [0-4], incidence rate ratio [95% confidence interval (CI)], 0.99 [0.69-1.44], p = 0.989, non-migraine headache group versus control group median [IQR], 0 [0-3] versus 1 [0-4], 0.71 [0.46-1.31], p = 0.156, headache not otherwise specified group versus control group median [IQR], 0 [0-4] versus 1 [0-4], 0.77 [0.45-1.31], p = 0.291. There was no significant correlation between headache-associated disability and the number of WMLs (0.07 [-0.30 to 0.17], rho [95% CI]). CONCLUSION: T2 hyperintense WMLs are common within the pediatric population and are not encountered more frequently in pediatric patients with migraine or other primary headache disorders. Thus, such lesions are presumably incidental and unlikely related to headache history.

A multicenter, randomized, double-blind, placebo-controlled, crossover trial to evaluate the efficacy and safety of zolmitriptan nasal spray for the acute treatment of migraine in patients aged 6 to 11 years, with an open-label extension.

OBJECTIVE: To evaluate the efficacy and safety of zolmitriptan nasal spray (ZNS) in the acute treatment of migraine headache in patients aged 6 to 11 years. BACKGROUND: Triptans have demonstrated efficacy in adults, but pediatric studies of these agents have largely failed and there are few triptan options for these patients. Because lack of response to 1 triptan does not necessarily preclude response to an alternate triptan, additional triptan options for pediatric patients are desirable. METHODS: This Phase 3, randomized, double-blind, placebo-controlled, multicenter crossover trial with an open-label extension enrolled patients aged 6 to 11 years with a diagnosis of migraine for ≥6 months and ≥16 headache-free days/month (N = 373). After a run-in period to eliminate placebo responders, 186 patients were randomized within their body weight stratum to ZNS followed by matching placebo, or placebo followed by matching ZNS. Patients <50 kg who were randomly allocated to ZNS were randomized to 5:1 to ZNS 2.5 or 1.0 mg; those ≥50 kg were randomized 5:1 to ZNS 5.0 or 2.5 mg. Patients had 6 weeks to treat 1 moderate to severe migraine headache and then crossed over to the alternate arm, during which they had 6 weeks to treat a second migraine attack. Patients could participate in a subsequent 6-month outpatient open-label extension. The primary efficacy endpoint was pain-free status at 2 h in patients treated with the high dose from each stratum. RESULTS: The trial was terminated early due to slow enrollment. Three hundred patients (mean age, 9 years) entered the placebo run-in period and 186 entered the double-blind period. Pain-free status at 2 h postdose was achieved by 45/133 (33.8%) and 30/128 (23.4%) of patients who received high-dose ZNS and placebo, respectively (p = 0.0777; odds ratio [OR] 1.51; 95% confidence interval [CI] 0.96, 2.38). Several secondary endpoints achieved statistical significance. There were few treatment-related adverse events and none led to discontinuation. ZNS retained efficacy and demonstrated a consistent safety profile throughout the 6-month open-label extension. CONCLUSION: The effect of high-dose ZNS on the primary endpoint of pain-free status at 2 h did not achieve statistical significance. ZNS was safe and well tolerated in this pediatric population.

Headache and Sleep Disturbances in the Pediatric Population.

The relationship between sleep disturbances and headaches in the pediatric population is bidirectional. Common underlying molecular mechanisms of sleep and headaches have been speculated to explain the clinical connection. We will summarize various sleep disturbances and their known relationships to headache, focusing on the pediatric population. Careful recognition and assessment of sleep disturbances in patients with headache is critical and may help guide treatment. First line therapies for sleep disturbances consist of behavioral approaches, though surgical and pharmacologic strategies are utilized in particular circumstances.

Telemedicine in Pediatric Headache: A Review and Practical Implementation.

PURPOSE OF REVIEW: The purpose of this review was to summarize the current literature about telemedicine in pediatric headache and to provide practical guidance for its implementation. RECENT FINDINGS: There are few studies dedicated to telemedicine in pediatric headache, and existing studies are small. Patients and families report high levels of satisfaction with telemedicine, and most are willing to continue telemedicine visits in the future. Telemedicine demonstrated similar reductions in headache frequency, severity, and duration as patients treated in-person. Remotely delivered psychologic interventions have some utility in reducing headache severity acutely. Families feel telemedicine reduces geographic and financial barriers to care. Telemedicine in pediatric headache is a growing field. While there is limited research available, it appears safe, efficacious, and feasible. Headache-related outcomes, including frequency, severity, and duration, were similar amongst telemedicine and in-person visits. Future studies should include larger sample sizes and detailed analysis of adverse outcomes.

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.

ED and Inpatient Management of Headache in Children and Adolescents.

PURPOSE OF REVIEW: Pediatric migraine is common, and appropriate abortive treatment is important to limit impact on school performance and mental health. This review will describe the latest evidence for abortive treatment in the emergency department and inpatient settings. RECENT FINDINGS: It is recognized that a protocol for emergency department treatment can increase efficacy and prevent admissions. These protocols commonly include a non-opioid analgesic and dopamine receptor antagonist. A novel approach to treatment with valproic acid is use of a continuous infusion. Administration of ketamine or propofol and peripheral nerve blocks could add more expedited treatment options to the armamentarium for pediatric migraine. There is increasing variety in the abortive treatment of pediatric migraine, but continued research is necessary for validation of these approaches.

A Randomized Trial to Evaluate OnabotulinumtoxinA for Prevention of Headaches in Adolescents With Chronic Migraine.

OBJECTIVE: As a post-approval commitment, this dose-ranging study was undertaken to evaluate efficacy and safety of onabotulinumtoxinA in adolescents. BACKGROUND: In adolescents, migraine is often undiagnosed or misdiagnosed and can present unique management challenges. OnabotulinumtoxinA was approved for prevention of chronic migraine (CM) in adults in 2010. METHODS: This multicenter, double-blind, parallel-group, randomized trial assessed a single treatment of onabotulinumtoxinA (155 U or 74 U) vs placebo (intramuscular saline) administered via the recommended fixed-dose fixed site paradigm in adolescents with CM aged 12 to <18 years. The primary efficacy measure was change in frequency of headache days from baseline at week 12; other measures included change in frequency of headache days at weeks 4 and 8 and change in frequency of severe headache days. Safety and tolerability were assessed. RESULTS: Of 125 randomized patients (onabotulinumtoxinA 155 U, n = 45; onabotulinumtoxinA 74 U, n = 43; placebo, n = 37), all were included in the primary efficacy analysis, and 115 (92.0%) completed the study. Lack of efficacy was the primary reason for discontinuing (n = 4; 3.2%); no patients discontinued because of adverse events. All treatments reduced frequency of headache days at week 12, with no significant differences between treatments. The mean (95% confidence interval) changes from baseline in the frequency of headache days during the 28-day period ending at week 12 (primary endpoint) were -6.3 (-8.5, -4.2), -6.4 (-8.8, -4.0), and -6.8 (-9.6, -4.1) days in the onabotulinumtoxinA 155 U, onabotulinumtoxinA 74 U, and placebo groups, respectively (P ≥ .474). All treatments reduced frequency of severe headache days and were well-tolerated; serious adverse events (n = 3) were considered unrelated to treatment and resolved without sequelae. The most commonly reported treatment-emergent adverse events were neck pain (n = 8), upper respiratory tract infection (n = 7), migraine, and nasopharyngitis (n = 5 each). CONCLUSION: Although this study did not meet its efficacy endpoints, onabotulinumtoxinA was well tolerated in this adolescent population. Given previous data demonstrating the benefits of onabotulinumtoxinA in adults with CM, additional studies with design modifications, including adequate statistical power, to assess the efficacy of multiple treatment cycles of onabotulinumtoxinA for CM prevention in adolescents may be informative.

Practice guideline update summary: Pharmacologic treatment for pediatric migraine prevention: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society.

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

Practice guideline update summary: Acute treatment of migraine in children and adolescents: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society.

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

Practice guideline update summary: Pharmacologic treatment for pediatric migraine prevention: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society.

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

Practice guideline update summary: Acute treatment of migraine in children and adolescents: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society.

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

Secondary Headaches in Children and Adolescents: What Not to Miss.

INTRODUCTION: Headaches are a common occurrence in childhood and adolescence. Most children presenting with a chief complaint of headache have a self-limited infectious disorder or primary headache syndrome that should not require extensive workup. PURPOSE OF REVIEW: Differentiating these conditions from other more serious causes of headache in children can sometimes be difficult. This article aims to provide information regarding "red flags" that should indicate a need for concern for disorders that require more urgent evaluation. RECENT FINDINGS: Long-held beliefs about specific "red flags" that have been analyzed in recent years as to their validity and new criteria for the diagnosis of idiopathic intracranial hypertension have been elaborated based on study. These publications are reviewed in this article. Knowledge of past and current literature on secondary headache in children, combined with thorough history taking and examination, should help determine when there is concern for a serious secondary cause for headache in children and adolescents and direct workup.

Prevention for Pediatric and Adolescent Migraine.

Children and adolescents can experience significant disability from frequent migraine. A number of tools have been developed to help quantify the impact of migraine in this population. Many preventative medications used in adults are routinely used to prevent migraines in children, although there has been less rigorous study. This article reviews the indications and evidence for the use of migraine preventatives, such as antidepressants, antihypertensives, anticonvulsants, antihistamines, and botulinum toxin, in this population.