Evaluating pediatric migraine requires a systematic approach involving the following steps:16,17
1. Medical history—Usually, a thorough headache history provides enough clues for accurate diagnosis.18 Questions (Table 2) are structured to identify more concerning headache patterns early in the process.19
Keep in mind that there are red flags that should trigger consideration of neuroimaging for suspicion of intracranial pathology (see “Red flags for considering neuroimaging,” page XX).20
2. Physical examination—This portion of the evaluation should include the following measurements/investigations:
· Take vital signs (including blood pressure, temperature, signs of hypertension or infection).
· Measure head circumference, even in older children.
· Palpate head and neck for sinus, jaw, ocular or temporomandibular joint tenderness, thyromegaly, or nuchal rigidity.
· Identify trigger points or areas of maximum tenderness to help determine nature of the pain.
· Check skin for signs of neurocutaneous syndromes, particularly neurofibromatosis and tuberous sclerosis, which are highly associated with intracranial neoplasms.
3. Neurologic examination—More than 98% of children with brain tumors who present with headache have objective neurologic findings.21 Look for abnormalities in these areas during the basic neurologic exam:
· Optic discs
· Eye movements
· Pronator drift
· Gait (including tandem gait)
· Deep tendon reflexes.
Routine neuroimaging is not indicated in children with recurrent headaches and normal examination. However, physicians should consider neuroimaging if certain warning signs appear:
· Recent onset of severe headache
· Change in headache quality or frequency
· Abnormal neurologic examination
· Coexistence of seizures.
4. Ancillary testing as indicated—No evidence supports the use of routine laboratory studies, lumbar puncture, or electroencephalogram (EEG) in headache-afflicted children with normal physical and neurologic findings. However, if findings in steps 1 to 3 warrant further exploration, consider appropriate modalities.
5. Imaging as indicated—Similarly, no evidence supports the use of routine neuroimaging in children with a history of recurring headaches who have a normal neurologic exam. Neuroimaging in children with headaches should be considered when findings in steps 1 to 3 warrant further investigation.17 More specifically, when the neurologic exam is abnormal, when other simultaneous neurologic concerns such as seizures are present, or when headache historical factors such as first, worst, or marked change in headache pattern are reported, neuroimaging should be considered. When considering neuroimaging, magnetic resonance imaging (MRI) would be the preferred imaging modality unless there is a concern for an acute or life-threatening etiology that warrants quick imaging such as computed tomography (CT).
Treatment of pediatric migraines requires a multitiered approach (Table 3), which tailors an individualized treatment plan to each patient's headache pattern and lifestyle and that can accommodate changes if needed.22 Headache frequency may spontaneously increase, for example, and patients may require higher or lower doses than for previous headaches, or, for more difficult headaches, combination therapy. Each child's degree of headache burden should determine how aggressively one treats and manages his or her headaches, considering the following factors:
· Headache frequency, duration and intensity;
· Patient's functional disability and pain tolerance;
· Patient's comorbidities; and
· Patient's quality of life.
Many patients with moderate-to-severe migraine respond well to oral treatment with analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) administered at the time of an attack (acute/abortive treatment; Table 4). Patients must be educated and able to use their medication as early during the headache as possible. This requires ready access to medications in school, home, and social situations:2,12,23 Patients also must avoid medication overuse, a known cause of headaches, by limiting analgesic and NSAID use to 2 to 3 days or less weekly. Keeping a headache diary can track drug use patterns.
Additional agents require caution. For example, aspirin-butalbital-caffeine is frequently prescribed for adult headaches, although, like other aspirin-containing products, it should be avoided in children aged younger than 16 years due to the risk of Reye syndrome.24 Always avoid opiates and other narcotics in children.
Physicians typically reserve serotonin 5-HT1B/1D receptor agonists (triptans; Table 522,26-30) for moderate-to-severe headaches unresponsive to over-the-counter analgesic therapy.12 Unlike ergot derivatives, triptans offer selective activity, along with well-established dosing regimens, safety, and tolerability.25 Sumatriptan, almotriptan, zolmitriptan, and rizatriptan have earned US Food and Drug Administration (FDA) approval for acute pediatric migraine.
All triptans activate the atypical 5-HT1B/1D receptor that has been implicated in the pathophysiology of migraine, and, to a lesser degree, other 5-HT receptors.23 They do this through 3 main mechanisms of action:31
· Cranial vasoconstriction;
· Peripheral trigeminal inhibition; and
· Inhibition of transmission through second-order neurons of the trigeminal cervical complex.
In 2006, the FDA warned consumers that taking triptans with selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephrine reuptake inhibitors (SNRIs) could raise users' risk of life-threatening serotonin syndrome. However, careful review of the available evidence has shown that this is not the case.32,33
Experts have suggested guidelines for triptan use in pediatric migraine (Table 6).2,12 Adverse effects of triptan generally last less than 30 minutes.
Additional treatment options
With few medications approved for pediatric migraine, physicians frequently prescribe drugs used for migraine in adults (Table 72,34).
Whereas no consensus exists for when and how to implement preventive therapy for migraine in children, various authors suggest considering prophylaxis in patients who experience at least 3 to 4 migraines monthly, and in those for whom acute treatments prove insufficient and/or poorly tolerated. Children who experience significant pain and/or disability also may warrant prophylaxis.12,35
Authors of the American Migraine Prevalence and Prevention (AMPP) trial recommend considering and offering prophylaxis to patients aged 12 years and older (Figure).36
The only agent the FDA has approved for preventive use in children is topiramate. Insufficient and often conflicting evidence notwithstanding, additional drugs commonly used for this purpose in children include antidepressives, antihypertensives, antiepileptics, antihistamines, and nutraceuticals (Table 812,22,37,38).
On the horizon: CGRP antagonists
A promising strategy for acute and preventive migraine treatment involves blocking calcitonin gene-related peptide (CGRP), a potent vasodilator whose concentration in the external jugular vein rises during migraine attacks39 and decreases in the serum after triptan administration and symptomatic relief.40 Developers of the following monoclonal antibodies targeting CGRP have filed for FDA review, with decisions expected in 2018:
Additional treatments under study specifically for pediatric headaches including migraine are propofol, prochlorperazine, dexamethasone, diclofenac, fentanyl, and several behavioral and nutraceutical approaches. As the array of interventions for preventing and treating pediatric migraine grows, timely and appropriate application of such agents will continue to reduce its burden.
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3. Abu-Arafeh I, Razak S, Sivaraman B, Graham C. Prevalence of headache and migraine in children and adolescents: a systematic review of population-based studies. Dev Med Child Neurol. 2010;52(12):1088-1097.
4. Stewart WF, Lipton RB, Celentano DD, Reed ML. Prevalence of migraine headache in the United States. Relation to age, income, race, and other sociodemographic factors. JAMA. 1992;267(1):64-69.
5. Migraine Research Foundation. Migraine in kids is not just a bad headache. Available at: http://migraineresearchfoundation.org/about-migraine/migraine-in-kids-and-teens/. Accessed May 15, 2018.
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20. Honig PJ, Charney EB. Children with brain tumor headaches. Distinguishing features. Am J Dis Child. 1982;136(2):121-124.
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27. Winner P, Rothner AD, Saper J, et al. A randomized, double-blind, placebo-controlled study of sumatriptan nasal spray in the treatment of acute migraine in adolescents. Pediatrics. 2000;106(5):989-997.
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29. Janssen Pharmaceuticals. Axert (almotriptan malate)—Highlights of prescribing information. http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/AXERT-pi.pdf. Revised May 2017. Accessed May 15, 2018.
30. Impax/AstraZeneca. Zomig (zolmitriptan)—Highlights of prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021450s008lbl.pdf. Revised June 2015. Accessed May 15, 2018.
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38. Sorge F, De Simone R, Marano E, Nolano M, Orefice G, Carrieri P. Flunarizine in prophylaxis of childhood migraine. A double-blind, placebo-controlled, crossover study. Cephalalgia. 1988;8(1):1-6.
39. Goadsby PJ, Edvinsson L, Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol. 1990;28(2):183-187.
40. Juhasz G, Zsombok T, Jakab B, Nemeth J, Szsolcsanyi J, Bagdy G. Sumatriptan causes parallel decrease in plasma calcitonin gene-related peptide (CGRP) concentration and migraine headache during nitroglycerin induced migraine attack. Cephalalgia. 2005;25(3):179-183.