Intractable Headache Disorders in Children

Educational Objectives

The goal of this program is to improve management of intractable headache disorders in children. After hearing and assimilating this program, the clinician will be better able to:

1. Identify pathophysiologic factors that contribute to migraine and intractable headache disorders.
2. Choose among various treatment options, such as cognitive behavioral therapy, stimulatory devices, and pharmacologic treatment, for management of migraine and intractable headache.

Summary

Primary disorders: new daily persistent headache — new onset of constant, daily unremitting headache (tension or migraine) for ≥3 mo; hemicrania continuum — persistent and unilateral; may present with autonomic symptoms; treat with indomethacin; status migranosis — lasts >72 hr; intractable chronic migraine — headache occurring ≥15 days/mo, ≥8 of which are migrainous; failure of 2 to 3 preventative medications; indomethacin-responsive headache disorders — trigeminal autonomic cephalalgia (TAC); short-lasting, unilateral, neuralgiform headache attacks with conjunctival injection and tearing (SUNCT); include paroxysmal and hemicrania continua, but not cluster headache

Pathophysiology: headache prodrome starts 36 hr before the migraine; factors — 38 genes associated with headache; environment includes barometric pressure and stress; metabolism includes relative hypoglycemia and neuroendocrine function; hormones; medications; migraine and headache disorders are a perfect storm of all factors combined, creating a metabolic crisis; neuroanatomy — the hypothalamus controls temperature, mood, and appetite; hypothalamic activation occurs 36 hr before a migraine (can be prevented in children with use of non-steroidal anti-inflammatory drugs [NSAID] or triptans); brainstem activation and cortical spreading depolarization occurs along with aura; calcitonin gene-related peptide (CGRP) neurotransmitters are released, causing migraine; triptans are antagonists of CGRP; each area is now considered a target for treatment; neuromodulators can be used in the cortex

Treatment: high-intensity interval training (HIIT) causes aerobic desensitization; autonomic nervous system (ANS) is responsible for headache disorders (heart rate variability can recalibrate the ANS); children are usually compliant with aerobic activity; lying flat in bed stimulates cortisol (vasodilator) release, which exacerbates headache disorders; prolonged fasting is not recommended; behavioral strategies — participate, distract, desensitize; limit catastrophic thinking as it is associated with worse outcomes in patients with headache

Trial of ≥3 rescue medication: helps determine failure of a medication; first-line is ibuprofen, followed by triptans (taken within the first hour of onset and tried ≥3 times); failure of 3 triptans suggests intractable disorder; trial a nutraceutical, eg, coenzyme Q₁₀ or riboflavin, then 1 mg/kg amitriptaline for ≈4 wk to separate from placebo, and 2 mg/kg topiramate for ≈1 mo (improvement should continue for the next 10 mo)

Pediatric Migraine Action Plan (PedMAP): can be provided for children to take to school; accommodates school, family, and child

Cognitive behavioral therapy (CBT): highly recommended, with strong evidence; cooccurring anxiety and/or depression exacerbates pain symptoms; should be provided to both parent and patient with the goal of reducing catastrophic thinking; emphasizes the impact of stress on pain and vice versa; aims to reduce negative or unhelpful thoughts that contribute to missing school; study by Powers et al — showed that amitriptyline plus pain CBT is associated with significantly better outcomes than amitriptyline with standard psychotherapy; study by Chow et al — 2 parental factors were shown to be significant in predicting worse outcomes in children; assessed parental avoidance behavior (questionnaire) and parent protective behavior (self-report) associated with child’s pain; parents who answer positively to the questionnaires have children with more disability

Triptans and tidans: serotonin-receptor agonists; triptans have vasogenic properties and are contraindicated in patients with sickle cell or an arterial disease; tidans are newer agents and are not contraindicated in these patients; however, tidans have not been approved for use in children; both are effective agents

CGRP inhibitors: eg, erenumab (Aimovig), galcanezumab (Emgality), fremanezumab (Ajovy); CGRPs are neural peptides located in the trigeminal nerve ganglion that dilate intracranial blood vessels and degranulate mast cells (causes inflammation) and are involved in pain transmission; CGRP is a biomarker for migraine; 4 agents are currently used as preventatives; once monthly injection of a CGRP inhibitor is associated with statistical reduction in the number of headache days per month; side effects (itchiness or pain at the injection site and constipation) occur in <5% of patients; multiple deaths in the elderly population have occurred because of bowel obstruction and perforation; there is higher incidence of hypertension, especially with erenumab; combination CGRP preventative plus a triptan works better than either agent alone; gepants — small-molecule CGRP-receptor antagonists (eg, ubrogepant [Ubrelvy], rimegepant [Nurtec]) that can be used for rescue; side effects (gastrointestinal upset) occur in only ≈2% of patients (same amount as the placebo group); there is no risk for overuse; remains in the bloodstream for ≈48 hr

Single pulse transcranial magnetic stimulation (sTMS): a magnetic device held against the back of the head stimulates depolarization of the cortex with strength similar to that of magnetic resonance imaging (MRI); the threshold for depolarization is lower in migraineurs, ie, providing stimulus multiple times per day increases threshold for pain; one study in 2018 showed that children can tolerate the stimulus

Remote electrical neuromodulator (REN): approved for use in ages ≥12 yr; the amount of energy provided by the armband can be controlled on a phone application; stimulates upper-arm peripheral nerves to induce conditioned pain (essentially exhausting the sensory cortex of the brain) for ≈24 hr; in one study, 71% of children had pain relief at 2 hr, and 35% were pain-free

Audience questions: increased screen time — a prior article shows no correlation with headache; COVID-19 pandemic — the number of patients with daily persistent headache has doubled since the start of the pandemic; anxiety and stress have also increased; being at home more often exposes children to many of stressors, eg, accommodations and resources provided by school are not available at home; MRI — shows no changes; in one study of ≈500 children with new daily persistent headache, imaging was performed in a very small percentage of patients, all of which had normal findings

Readings

Brandes JL. The influence of estrogen on migraine. JAMA. 2006; 295:1824-1830; doi: 10.1001/jama.295.15.1824; Chow ET, Otis JD, Simons LE. The longitudinal impact of parent distress and behavior on functional outcomes among youth with chronic pain. J Pain. 2016;17(6):729-738. doi:10.1016/j.jpain.2016.02.014; Durham PL. CGRP-receptor antagonists — a fresh approach to migraine therapy? N Engl J Med. 2004; 350:1073–1075; doi: 10.1056/NEJMp048016; Fillingim RB, Loeser JD, Baron R, et al. Assessment of chronic pain: domains, methods, and mechanisms. J Pain. 2016; 17:T10-20; doi: 10.1016/j.jpain.2015.08.010; Irwin SL, Qubty W, Allen IE, et al. Transcranial magnetic stimulation for migraine prevention in adolescents: a pilot open-label study. Headache. 2018; 58:724-731; doi: 10.1111/head.13284; Hanssen H, Minghetti A, Magon S, et al. Superior effects of high-intensity interval training vs. moderate continuous training on arterial stiffness in episodic migraine: a randomized controlled trial. Front Physiol. 2017; 8:1086; doi: 10.3389/fphys.2017.01086; Li H, Yu G, Dong C, et al. PedMap: a pediatric diseases map generated from clinical big data from Hangzhou, China. Sci Rep. 2019; 9:17867; doi: 10.1038/s41598-019-54439-w; Ng QX, Venkatanarayanan N, Kumar L. A systematic review and meta-analysis of the efficacy of cognitive behavioral therapy for the management of pediatric migraine. Headache. 2017;57(3):349-362. doi:10.1111/head.13016; Powers SW, Kashikar-Zuck SM, Allen JR, et al. Cognitive behavioral therapy plus amitriptyline for chronic migraine in children and adolescents: a randomized clinical trial. JAMA. 2013; 310:2622-2630; doi: 10.1001/jama.2013.282533; Starling AJ, Tepper SJ, Marmura MJ, et al. A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE Study). Cephalalgia. 2018; 38:1038-1048; doi: 10.1177/0333102418762525; Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017; 16:425-434; doi: 10.1016/S1474-4422(17)30083-2.

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, members of the faculty and planning committee reported nothing to disclose. In his lecture, Dr. DiSabella presents information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. DiSabella was recorded at the Hot Topics in Pediatrics, held July 22-24, 2021, in Lake Buena Vista, FL, and presented by Nemours Children's Health System. For information on future CME activities from this presenter, please visit www.nemours.org/education/cme. Audio Digest thanks Dr. DiSabella and Nemours Children's Health System for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

PD674302

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.