Effectiveness and Tolerability of Anti-Calcitonin Gene-Related Peptide Therapy for Migraine and Other Chronic Headaches in Adolescents and Young Adults: A Retrospective Study in the USA.

This retrospective study assesses the efficacy and tolerability of anti-calcitonin gene-related peptide (anti-CGRP) therapy in adolescents and young adults (ages 12-21) with migraine and chronic daily headaches unresponsive to standard treatments. Migraines in this demographic significantly impair school performance, self-esteem, psychological well-being, and cognitive health. These young patients are also particularly sensitive to the side effects of conventional medications, which are often prescribed off-label and come with high insurance denial rates. Medication overuse, including analgesics, triptans, and NSAIDs, is prevalent due to treatment failures. Elevated plasma CGRP levels observed during migraines suggest that anti-CGRP therapies, successful in adult populations, may also benefit this younger age group. Over a three-year period, patients at a specialized pediatric headache center were evaluated for the impact of anti-CGRP treatments, including monoclonal antibodies (erenumab, fremanezumab, and galcanezumab) and small-molecule CGRP receptor antagonists (ubrogepant, rimegepant, and atogepant), administered either alone or in combination with OnabotulinumtoxinA. Data were extracted from the hospital's electronic medical records, and patient progress was consistently documented using a structured template for each clinic visit. Additional patient satisfaction data were collected via telephone follow-ups and patient message reviews. The study included 23 patients, primarily treated for chronic migraine (CM) (78.3%), with a smaller subset addressing episodic migraine (EM), new daily persistent headaches (NDPHs), and post-traumatic headaches (PTHs). Comprehensive demographic and clinical data, including age, treatment duration, history of preventive treatment failures, and comorbidities like psychiatric conditions and sleep disorders, were collected. Anti-CGRP therapies, particularly when combined with traditional treatments or OnabotulinumtoxinA, resulted in significant improvements: 91.3% of patients experienced reduced migraine duration and intensity, 82.6% reported improvements in other bothersome symptoms, and 73.9% saw an improved response to rescue medications. Additionally, 78.3% of patients reported a reduction in their use of rescue medications per week by more than 50%, and emergency room visits were reduced for 56.5% of patients. Significant reductions in headache days were observed in 82.6% of patients after one month and 87% after three months, with nearly 40% experiencing more than a 50% reduction in both periods. The greatest benefits were observed in patients treated for more than six months. Adverse effects were minimal, with 95.7% of patients reporting no side effects, and patient satisfaction was high, with 69.6% opting to continue treatment. Overall, this study highlights the substantial potential of anti-CGRP therapy in improving outcomes for adolescents and young adults with CM and EM, offering a promising approach for a demographic that faces considerable challenges with conventional treatment options. However, further research is needed to confirm these findings and expand clinical applications in this age group.

Sex and age-related patterns in pediatric primary headaches: observations from an outpatient headache clinic.

Background: Age reportedly affects headache prevalence differently in boys and girls. However, little empirical data exists regarding pediatric headache prevalence and headache-related burden in children and adolescents according to age and sex. In the present study, we considered age and sex while evaluating the distribution, characteristics, and impairment of primary headache disorders at a pediatric headache center in Germany. Methods: Medical records of children and adolescents attending the headache clinic of the Interdisciplinary Pain Center of the Carl Gustav Carus University Hospital in Dresden during the period 2015-2022 were retrospectively grouped and analyzed depending on age (< or ≥14 years) and sex. Results: The study population consisted of 652 children and adolescents, aged between 3 and 18 years. Almost two-thirds of the patients (≈60%) were females, and almost two-thirds of these females (58%) were ≥14 years of age. Generally, the most prevalent headache diagnoses as defined by the International Classification of Headache Disorders 3rd edition were episodic migraine without aura and the combination of tension-type headache and episodic migraine with or without aura i.e., mixed-type headache (each ≈27%). In the younger group (<14 years), the mixed-type headache was the most prevalent in girls (28.6%), whereas, for boys, episodic migraine without aura was the most prevalent headache diagnosis (47.4%). In the older group (≥14 years), the mixed-type headache continued to be the most prevalent for girls (30%), and it became the most prevalent for boys (26.3%). Before the age of 14, about 16% of children were severely affected by their headaches. After the age of 14, this proportion increased to roughly one-third (33%) of adolescents, driven mainly by teenage girls (26%) who were severely affected by their headaches. Furthermore, the prevalence of comorbidities was significantly higher among girls (67%), particularly in the adolescent group (74%). Conclusions: Our data shows that headache disorders in a specialized pediatric clinic impose a significant burden, especially among teenage girls indicating high therapy needs. Enhancing awareness of early diagnosis and preventive care is crucial to mitigate the development of chronic headaches, and mitigate their adverse effects on life quality and educational capability.

Pediatric post-dural puncture headache and paraplegia.

A cerebrospinal fluid (CSF) leak developed in a 14-year-old girl and a 12-year-old boy following a diagnostic lumbar puncture. Two days and sixteen years later, respectively, paraplegia developed due to a functional disorder. Imaging revealed an extensive extradural CSF collection in both patients and digital subtraction myelography was required to pinpoint the exact site of a ventral dural puncture hole where the lumbar spinal needle had gone "through and through" the dural sac. The CSF leak was complicated by cortical vein thrombosis in one patient. Both patients underwent uneventful surgical repair of the ventral dural puncture hole with prompt resolution of the paraplegia. Iatrogenic ventral CSF leaks may become exceptionally long standing and may be complicated by paraplegia on a functional basis both in the acute and chronic phases.

Exploring downstream effects of gender roles in healthcare decision-making and relationships within systems: A cross-sectional analysis of openness to treatment in pediatric headache.

OBJECTIVE: Socio-culturally defined identity factors present significant and often understudied influences on the experience, management, and treatment of chronic pain. For instance, there exist societal narratives about how males and females are expected to experience and express pain. Such gender roles may impact youth and caregiver openness to individual multidisciplinary treatments for pediatric headache. METHODS: In this cross-sectional study, participants (N = 1087 youth/caregiver dyads, Mage = 14.5 years, 71% female, 97% cisgender, 77% White) completed a series of questionnaires, including Openness to Headache Treatment (OHT), upon presenting for initial multidisciplinary evaluation of chronic headache. Pearson correlations, independent samples t-tests and hierarchical regressions were used to analyze potential gender differences in youth and caregiver openness, as well as its relationships with pain-related and psychological factors. RESULTS: Overall, female youth and their caregivers were more open to headache treatment, broadly and for individual interventions, when compared to male counterparts. Caregiver distress related to their child's headaches (i.e., fear and avoidance) was significantly correlated with openness in female youth and their caregivers, but not males. CONCLUSION: Gendered patterns in healthcare decision-making in youth and caregivers provide insight on individual, societal, and systemic gender bias.

Persistent Elevation of Opening Pressure Despite Treatment and Symptom Resolution in Pediatric Intracranial Hypertension.

BACKGROUND: Currently no guidelines for repeating a lumbar puncture to guide management in primary intracranial hypertension (PIH) exist. METHODS: An institutional database of patients 18 years and younger followed in the institution's pediatric intracranial hypertension clinic was examined for opening pressure changes in PIH at diagnosis, before medication wean, and following medication wean, as well as to examine whether measurements at the time of diagnosis differed between those with and without disease recurrence. RESULTS: Forty-two patients were included in this study; 36% were male and the mean age at diagnosis was 11.01 years. Treatment duration averaged 9.68 months in those without recurrence and 8.5 months in those with recurrence. Average body mass index percentile of patients with disease recurrence was 83.7 and 72.1 in those without recurrence (P = 0.16). Average opening pressure values of all patients at diagnosis, prewean, and postwean was 36.53 cm H2O, 30.7 cm H2O, and 31.1 cm H2O, respectively. There was no statistically significant difference in opening pressures across these time points (P = 0.14). The change in opening pressure from diagnosis to postwean was statistically significant with a reduction of 5.18 cm H2O (P = 0.04). There was no statistical difference between change in opening pressure at diagnosis versus postwean between those with and without recurrence (P = 0.17). CONCLUSIONS: This clinical observational study suggests that mean opening pressure measurements in patients with PIH remain elevated both before and after medication wean despite papilledema resolution and patient-reported PIH symptoms. Clinically, this suggests that other features such as signs of optic disc edema and symptoms should be used to inform a clinical determination of disease recurrence and treatment course.

Screen time and pediatric headache: A scoping review of the literature.

OBJECTIVE: The aim of this study was to summarize the evidence regarding screen use as a contributing factor in pediatric headache and migraine. BACKGROUND: Screen exposure is often reported as a headache trigger, though there is no current consensus in terms of how screen type, duration, or frequency influences pediatric headache and the associated burden of disease. METHODS: A systematic search in PubMed, Scopus, Cochrane Library, ProQuest Health and Medical Database, and Google Scholar was performed through November 2022 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. All English-language articles of pediatric patients aged ≤18 years evaluating screen use in relation to headache were included. RESULTS: A total of 48 studies were included. Nearly all studies were cross-sectional and represented international samples. The strongest association between screen use and headache found was for duration of use, and computer use emerged as the most common device type related to headache. While there were mixed findings related to screen use and specific headache diagnosis, migraine appeared to confer a higher risk. Across studies, there were insufficient data to assess the impact of screen use on headache frequency or headache-related disability. Several studies demonstrated changes in screen use and headache patterns related to the COVID-19 pandemic and computer vision syndrome was commonly reported. CONCLUSIONS: While there is preliminary evidence supporting possible associations between screen use and pediatric headache, there are several limitations in the present review including a lack of prospective and randomized controlled trials to better demonstrate causal relationships as well as methodological limitations with significant variability in how both headache and screen use are defined and measured. Future studies including real-time screen use and device monitoring are needed to better understand the influence of screen use behaviors on pediatric headache and to help further define best-use guidelines around these technologies.

[Gender-specific results of the Dresden children and adolescents headache program DreKiP]. / Geschlechtsspezifische Ergebnisse des Dresdner Kinder- und Jugendkopfschmerzprogrammes DreKiP.

BACKGROUND: Girls and women are more frequently affected by headache than boys and men. The influence of gender on the effectiveness of headache therapies has so far been hardly investigated. We examined gender differences in the outpatient multimodal Dresden Child and Adolescent Headache Program DreKiP. METHODS: We treated 140 patients with primary headache in a 15-hour structured group program. At baseline (T0) and six (T1) and twelve months (T2) after the end of the program, data on headache-related limitation of daily activities (PedMIDAS) as well as headache frequency, intensity, and pain-related disability (P-PDI) were collected. Retrospectively, these data were analyzed separately for girls and boys. RESULTS: For 91 patients (9-19 years, median = 15; 71.4 % female) data were available for at least two measurement time points. Girls showed significantly higher headache frequency than boys at all time points (median headache days/last three months at T0: ♀ 43, ♂ 20; T1: ♀ 32, ♂ 12; T2: ♀ 28, ♂ 9) as well as numerically higher headache-related limitation of daily life. There were significant effects over time with a decrease in headache frequency (F (2.88) = 5.862; p = 0.004) and improvement in daily functioning (F (2.92) = 5.340; p = 0.006). There was no gender-specific treatment response. DISCUSSION: The DreKiP therapy shows effects in girls and boys with primary headache. Higher headache frequencies and everyday life restrictions in girls may have hormonal but also psychosocial causes and should be addressed in educational measures.

Pediatric headache patient with cerebral abscesses: a brief review of the literature and case report.

BACKGROUND: Pediatric headache is a common cause of pediatric emergency department (ED) visits, and 8.8% of cases require imaging. Alarmingly, 12.5% of imaged cases have a pathologic cause. A pediatric patient with a complicated medical history presented to the pediatric ED with multiple cerebral abscesses. The possible causes and contributors to this rare cause of pediatric headache and a review of pediatric headache emergency management are presented.Case Presentation: A 12-year-old male patient with a complex medical and surgical history, including post-repair pulmonary valve stenosis, visited the pediatric ED for intractable and worsening left frontoparietal headache, refractory to ibuprofen, for 6 days. A physical examination revealed severe photophobia and restlessness secondary to severe head pain. Non-contrast brain computed tomography demonstrated two round, bilateral, parietal hypodense lesions with surrounding vasogenic edema. The lesions were consistent with abscesses on magnetic resonance imaging. Eventually, the patient underwent successful surgical abscess drainage and made a full recovery. The patient was lost to follow-up; therefore, no causative bacterial species was determined. CONCLUSION: Managing pediatric headache in emergency settings requires a robust history and physical examination. Cerebral abscesses are an infrequent but fatal cause of pediatric headache and therefore should be considered among the differential diagnoses.

Advances in the Acute and Preventive Treatment of Pediatric Migraine.

PURPOSE OF REVIEW: Headaches are common in children and adolescents. Treatments for debilitating migraine are often not FDA approved or lack evidence of efficacy for children. This narrative review looks at the evidence for acute and preventative pharmacologic and non-pharmacologic treatment of pediatric migraine, as well as reviewing any recent or ongoing clinical trials. RECENT FINDINGS: Studies have been published on pharmacological treatments for headache, as well as non-pharmacological treatments. Recent findings in pediatric migraine using onabotulinumtoxinA, calcitonin gene related peptide antagonists, interventional procedures, and devices are reviewed. Pharmacologic as well as non-pharmacologic approaches for the prevention and treatment of migraine show safety and efficacy data that is promising. These treatments should be incorporated in a multi-modal approach to the management of pediatric migraine. Continued studies, prospective and randomized, are needed to further assess these newer treatments for migraine in the pediatric setting.

Prevalence and Contextual Factors of Juvenile Fibromyalgia in a Population-Based Italian Sample of Children and Adolescents.

Juvenile Fibromyalgia (JFM) is poorly known, leading to delay in the identification of the syndrome. On the other hand, early diagnosis in children is important to prevent the worsening of the disease. This study aims to estimate the prevalence of JFM in an Italian population-based convenience sample, using different criteria (2010 and 2016 ACR, Yunus and Masi), by involving family pediatricians. It also aims to assess the relationships between JFM and contextual factors of the children and their parents, as well as to raise awareness of JFM among pediatricians. Children's data were collected using an ad hoc electronic questionnaire. Overall, 7275 questionnaires were collected (48.5% females; mean age: 8.2 ± 3.6 years). Thirty-eight children (0.5%) met the 2010 ACR criteria, and 4 (0.1%) met the 2016 ACR criteria. The likelihood of meeting the 2010 ACR criteria was significantly higher for children older than 8 years (OR: 2.42), those who had injuries during the leisure time that caused persistent pain (OR: 6.49), whose parents (at least one) had a diagnosis of fibromyalgia (OR: 2.54) or diffuse pain (OR: 9.09). In conclusion, 2010 ACR criteria are confirmed as the more appropriate for children and adolescents and the analysis of contextual factors suggests the need for family pediatricians to pay particular attention to the most important predictors of JFM.

Longitudinal trajectories of posttraumatic headache after pediatric mild traumatic brain injury.

OBJECTIVE: This prospective, longitudinal cohort study examined the trajectory, classification, and features of posttraumatic headache after pediatric mild traumatic brain injury. METHODS: Children (N = 213; ages 8.00 to 16.99 years) were recruited from two pediatric emergency departments <24 hours of sustaining a mild traumatic brain injury or mild orthopedic injury. At 10 days, three months, and six months postinjury, parents completed a standardized questionnaire that was used to classify premorbid and posttraumatic headache as migraine, tension-type headache, or not otherwise classified. Multilevel mixed effects models were used to examine posttraumatic headache rate, severity, frequency, and duration in relation to group, time postinjury, and premorbid headache, controlling for age, sex, and site. RESULTS: PTH risk was greater after mild traumatic brain injury than mild orthopedic injury at 10 days (odds ratio = 197.41, p < .001) and three months postinjury (odds ratio = 3.50, p = .030), especially in children without premorbid headache. Posttraumatic headache was more frequent after mild traumatic brain injury than mild orthopedic injury, ß (95% confidence interval) = 0.80 (0.05, 1.55). Groups did not differ in other examined headache features and classification any time postinjury. CONCLUSIONS: Posttraumatic headache risk increases after mild traumatic brain injury relative to mild orthopedic injury for approximately three months postinjury, but is not clearly associated with a distinct phenotype.

Olfactory training reduces pain sensitivity in children and adolescents with primary headaches.

Objective: Headache prevalence among children and adolescents has increased over the last few years. Evidence-based treatment options for pediatric headaches remain limited. Research suggests a positive influence of odors on pain and mood. We investigated the effect of repeated exposure to odors on pain perception, headache-related disability, and olfactory function in children and adolescents with primary headaches. Methods: Eighty patients with migraine or tension-type headache (mean 13.1 ± 3.29 years) participated, of whom 40 underwent daily olfactory training with individually selected pleasant odors for 3 months and 40 received state-of-the-art outpatient therapy as a control group. At baseline and after a 3-month follow-up, olfactory function [odor threshold; odor discrimination; odor identification; comprehensive Threshold, Discrimination, Identification (TDI) score], mechanical detection and pain threshold (quantitative sensory testing), electrical pain threshold, patient-reported outcomes on headache-related disability [Pediatric Migraine Disability Assessment (PedMIDAS)], pain disability [Pediatric Pain Disability Index (P-PDI)], and headache frequency were assessed. Results: Training with odors significantly increased the electrical pain threshold compared to the control group (U = 470.000; z = -3.177; p = 0.001). Additionally, olfactory training significantly increased the olfactory function (TDI score [t(39) = -2.851; p = 0.007], in particular, olfactory threshold, compared to controls (U = 530.500; z = -2.647; p = 0.008). Headache frequency, PedMIDAS, and P-PDI decreased significantly in both groups without a group difference. Conclusions: Exposure to odors has a positive effect on olfactory function and pain threshold in children and adolescents with primary headaches. Increased electrical pain thresholds might reduce sensitization for pain in patients with frequent headaches. The additional favorable effect on headache disability without relevant side effects underlines the potential of olfactory training as valuable nonpharmacological therapy in pediatric headaches.

Acute Bacterial Sinusitis With Epidural and Subdural Involvement.

Sinusitis is a common childhood infection with potential for rare intracranial complications. These neurologic sequelae can lead to serious morbidity and mortality if not addressed promptly. We describe a case of suspected sinusitis in a 13-year-old male complicated by a superior sagittal sinus thrombosis along with subdural and epidural empyemas.

Sumatriptan as a First-Line Treatment for Headache in the Pediatric Emergency Department.

BACKGROUND: Headache is a common presenting condition for patients seen in the pediatric emergency department (ED). Intranasal (IN) sumatriptan is a well-tolerated and safe abortive treatment for migraine headache, but it is infrequently administered in pediatric EDs. In this study we characterize an ED migraine pathway that uses IN sumatriptan as a first-line treatment. METHODS: We performed retrospective chart analysis from a single center, reviewing a cohort of patients treated on an ED migraine pathway between October 2016 and February 2020. We reviewed patient demographics, clinical characteristics, treatment patterns, change in pain scores, sumatriptan prescriptions at discharge, length of stay (LOS), ED charges, and unexpected return visits. RESULTS: A total of 558 patients (aged six to 21 years, 66% female) were included in this study. Overall, the median pretreatment pain score was 7 (interquartile range [IQR]: 5 to 8) and the median post-treatment pain score was 2 (IQR: 0 to 4). Forty-eight percent of patients received IN sumatriptan in the ED, and 36% of those who received sumatriptan were prescribed oral sumatriptan at discharge. When intravenous (IV) access was obtained for headache management, this was associated with a significantly longer LOS and higher ED charges. CONCLUSIONS: IN sumatriptan shows promise as a feasible and potentially effective first-line treatment for pediatric migraine in the ED that could reduce the need for IV therapies, shorten LOS, and lower ED charges. Further research is needed to determine the efficacy of IN sumatriptan relative to other common first-line therapies used to treat pediatric migraine in the ED.

Treatment of migraine in children and adolescents. The state of the art / Tratamento da enxaqueca em crianças e adolescentes. O Estado da arte

Introduction: Headaches and migraine are common in the pediatric population, being one of the most frequent symptoms reported in practice. Additionally, it is a considerably disabling condition, which brings significant burden and impairs several aspects of a child or adolescent's life, such as mental and physical health, executive functioning, school performance. Children and adolescents with migraine have higher risk of psychiatric comorbidities and psychosocial adjustment difficulties, which, in turn, compromise even more patient's well functioning. Objective:The present article provides the clinician with a straightforward and evidence-based approach to migraine treatment in this age group. Comment: Treatment of migraine in children and adolescents requires a systematic and thorough approach. Clinicians should keep in mind the important burden migraine brings to a child's life, thus investigate, and properly manage comorbidities presented. Patient and parents' education is a meaningful part of the treatment. Moreover, non-pharmacological treatments, such as healthy lifestyle habits, behavioral interventions may also play beneficial roles. When preventive treatment is indicated, it should be tailored considering drug's profile of effectiveness and safety, as well as patient's comorbidities. Lack of evidence in this context must not translate in lack of action by the clinician, since there may be a relevant burden associated. Therefore, reasoning for the perspicacious clinician is of fundamental importance and may influence positively the outcomes.

Introdução: Dores de cabeça e enxaqueca são comuns na população pediátrica, sendo um dos sintomas mais frequentes relatados na prática. Além disso, é uma condição consideravelmente incapacitante, que traz sobrecarga significativa e prejudica diversos aspectos da vida de uma criança ou adolescente, como saúde mental e física, funcionamento executivo, desempenho escolar. Crianças e adolescentes com enxaqueca apresentam maior risco de comorbidades psiquiátricas e dificuldades de ajustamento psicossocial, o que, por sua vez, compromete ainda mais o bom funcionamento do paciente. Objetivo: O presente artigo fornece ao médico uma abordagem simples e baseada em evidências para o tratamento da enxaqueca nesta faixa etária. Comente: O tratamento da enxaqueca em crianças e adolescentes requer uma abordagem sistemática e minuciosa. Os médicos devem ter em mente o importante fardo que a enxaqueca traz à vida de uma criança, investigando e gerenciando adequadamente as comorbidades apresentadas. A educação do paciente e dos pais é uma parte significativa do tratamento. Além disso, os tratamentos não farmacológicos, como hábitos de vida saudáveis ​​e intervenções comportamentais, também podem desempenhar papéis benéficos. Quando indicado tratamento preventivo, este deve ser adaptado considerando o perfil de efetividade e segurança do medicamento, bem como as comorbidades do paciente. A falta de evidências neste contexto não deve traduzir-se em falta de ação por parte do médico, uma vez que pode haver um ónus relevante associado. Portanto, o raciocínio do clínico perspicaz é de fundamental importância e pode influenciar positivamente os resultados.

Aligning with Patients and Families: Exploring Youth and Caregiver Openness to Pediatric Headache Interventions.

Primary headache disorders are common yet underestimated in youth, resulting in functional disability, decreased quality of life, and caregiver burden. Despite the ubiquity of options, adherence remains challenging for families. One potential factor impacting willingness to engage in recommended treatments is openness. This study explored openness to multidisciplinary headache interventions and the relationships with demographic, pain-related, and psychological variables, among youth and their caregivers. Participants (n = 1087) were youth/caregiver dyads presenting for initial headache evaluation. They completed assessments of openness to headache treatments, medical information, functional disability, and pain-related distress. Overall openness was moderately high for youth and caregivers, and highly correlated between them (r = 0.70). Relationships between youth/caregiver openness to specific interventions were moderate-high (r = 0.42-0.73). These were stronger for interventional techniques but weaker for lifestyle changes. In hierarchical regression models predicting youth and caregiver openness, we found that counterpart openness accounted for the largest portion of variance in their own openness (31-32%), beyond demographic (3%), pain-related (10%), and psychological variables (2-3%). Our findings highlight the importance of involving caregivers in pediatric headache management, given their influence on youth openness and potential involvement in adherence. Awareness of youth/caregiver openness may guide clinicians providing recommendations.

Neuroimaging in Pediatric Headache.

Headache represents one of the most common disorders in childhood and leads to nearly half a million visits to the physician's office or emergency department every year. Although the estimated prevalence is around 58.4%, the actual incidence of headache in the pediatric population might be underestimated, given only a percentage of cases seek medical attention. The first step in the evaluation of pediatric headache is a detailed clinical history and relevant clinical examinations. AAN and ACR do not recommend neuroimaging for patients with primary headache. However, neuroimaging becomes mandatory in presence of red flags to rule out the underlying cause.