Reena G. Rastogi, MD; Robert D. Little, MD
According to the World Health Organization, migraine is the third most common medical condition worldwide. Migraine is the second leading cause of disability among adolescents and young adults.1,2 Most people with migraine have onset prior to 18 years of age, and it is one of the most common reasons for referral to neurology. The condition results in frequent morbidity in a number of children, excessive school absences and a lower quality of life. The financial burden of the management and treatment of pediatric headache in the United States is also significant, with an estimated national expenditure of approximately $1.1 billion annually.3
Science of Migraine
The past few years have seen an evolving understanding of migraine. There has been tremendous progress in the treatment of migraines based on newer understanding of the underlying pathophysiology of the disorder. Despite emerging innovative migraine-specific treatments, there is an ongoing need for improved prophylactic and abortive therapies, especially in the pediatric age group. Therapeutic discovery remains a rapidly advancing area of research.
Migraine is a complex disorder involving large neuronal networks with multiple peripheral and central factors. Activation of the trigeminal ganglion has long been known to trigger the headache phase of a migraine attack. A better understanding of the peripheral mechanisms that lead to this activation has identified many possible targets for novel treatments. Central sensitization, which mediates chronification of migraine, remains less well understood, but newer information from functional imaging studies may reveal other therapeutic targets.
CGRP (calcitonin gene-related peptide) has been known to play a major role in migraine for many years. It is released at the trigeminal ganglion as part of the triggering of the headache phase of migraine, and it is chronically elevated in chronic migraine. However, efforts to develop a clinical treatment targeting CGRP have been elusive. Recently, several antibodies to CGRP or its receptor have received FDA approval for prevention of migraine headaches in adults. These treatments involve monthly injections that have been shown to significantly reduce the number of headache days in patients with migraine. These treatments have been very well tolerated with a very low rate of side effects. Unfortunately, data in the pediatric population are lacking.
At Phoenix Children’s, we are participating in a phase III clinical trial evaluating the use of one of these antibodies (galcanezumab) for prevention of migraine in children and adolescents. If this study confirms the effectiveness of this treatment, it may offer an important additional resource for pediatric patients suffering from migraine headaches.
Lasmiditan is a new acute treatment for migraine with a novel mechanism of action. It is a 5HT-1F receptor agonist, which is a unique target for acute therapies for migraine. Unlike the triptans, it does not cause vasoconstriction, so it may be a good alternative for those patients who do not tolerate triptans or for whom a triptan is contraindicated. This may potentially provide a more effective and better tolerated treatment. Phoenix Children’s is also participating in a phase III clinical trial in children and adolescents to determine if lasmiditan is effective for the acute treatment of migraine.
Most of the current data for pediatric migraine are centered around non-pharmacologic treatments, including mindfulness-based therapy and cognitive behavioral therapy (CBT). Phoenix Children’s headache specialists recently published a review of the evidence behind these treatment options for children.4 The Complex Headache Clinic at Phoenix Children’s provides a multidisciplinary approach to exploring pharmacologic and non-pharmacologic treatment options with a neurologist and a psychologist, including mindfulness, relaxation, deep breathing and CBT. This is one of the few multidisciplinary clinics in the nation that offers access to a pediatric psychologist for headache patients.
Phoenix Children’s is also involved in a Patient-Centered Outcomes Research Institute (PCORI) study based out of Cincinnati Children’s Hospital evaluating treatment with amitriptyline + telehealth CBT versus telehealth CBT alone, emphasizing the importance of further studies to evaluate the efficacy of non-pharmacologic treatments such as cognitive behavioral therapy in the pediatric population.
Neuromodulation devices have become more popular over the last several years, and with recent advances in pediatric studies, these are now available to the adolescent population. These treatments provide a practical and alternative option for patients who prefer to avoid using pharmacologic agents for migraine management. In 2021, the FDA authorized the use of gammaCore™, a noninvasive vagal nerve stimulator (nVNS), for adolescents aged 12 to 17 years for migraine prevention. This device is thought to modulate pain through effects on the autonomic system, inhibition of cortical spreading depression and regulation of neurotransmitters.5 Remote electrical neuromodulation (REN)6 is a novel acute treatment for migraine that provides peripheral nerve stimulation in the upper arm to induce conditioned pain modulation. The Nerivio® device was also FDA approved for acute treatment of migraine in adolescents ages 12 to 17 years in 2021.
In addition, procedures such as sphenopalatine ganglion (SPG) blocks and occipital nerve blocks are offered for acute treatment of headaches in our procedure clinics, although evidence in the pediatric population is limited. A study performed at Phoenix Children’s evaluating the early use of SPG blocks in the pediatric emergency room found that the SPG block is a safe, well-tolerated and effective treatment option for migraine and can reduce the emergency department length of stay.7
We have invested heavily in leveraging and building digital capabilities that will enable a new care and operating model, access to patient care and improved clinical practice and outcomes. A unique aspect of our headache program is the development and use of a real-time patient data headache dashboard. The dashboard is being used to improve operational efficiencies and drive clinical excellence by tracking headache frequency, PedMIDAS disability scores, emergency room visits and hospital admissions for headache patients.
These data facilitate quality improvement and research initiatives, for example, tracking the safety and efficacy of migraine treatment by telehealth virtual visits versus in-person clinic visits. This is being done by digitally tracking all emergency room visits and/or hospital admissions for all headache patients withing 45 days of an outpatient encounter. Headache providers receive automatically generated emails once a week identifying their patients who meet these criteria and are easily able to identify potential “failure of care” with technology-assisted support.
- Steiner TJ, Stovner LJ, Jensen R. et al. Migraine remains second among the world’s causes of disability, and first among young women: findings from GBD2019. J Headache Pain 2020;21:137
- Vos T, Lim SS, Abbafati C, et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 2020;396:1204-1222.
- Law EF, Palermo TM, Zhou C, Groenewald CB. Economic Impact of Headache and Psychiatric Comorbidities on Healthcare Expenditures Among Children in the United States: A Retrospective Cross-Sectional Study. Headache. 2019;59:1504-1515.
- Rastogi RG, Arnold TL, Borrero-Mejias C, Hastriter EV, Hickman C, Karnik KT, Lewis KS, Little RD. Non-pharmacologic and Mindful-Based Approaches for Pediatric Headache Disorders: a Review. Curr Pain Headache Rep. 2021;25:78.
- Silberstein SD, Yuan H, Najib U, Ailani J, Morais AL, Mathew PG, Liebler E, Tassorelli C, Diener HC. Non-invasive vagus nerve stimulation for primary headache: A clinical update. Cephalalgia 2020;40:1370-1384.
- Hershey AD, Lin T, Gruper Y, Harris D, Ironi A, Berk T, Szperka CL, Berenson F. Remote electrical neuromodulation for acute treatment of migraine in adolescents. Headache 2021;61:310-317.
- Haywood M, Mecham C, Rastogi R, Mirea L, Bulloch B. Early Utilization of SPG Block for the Treatment of Acute Migraine Headache in the Pediatric Emergency Department (4829). Neurology 2021;96 (15 Supplement);4829.