Pediatric migraine: Diagnostic criteria and treatment

Table 1

Table 2

Table 3

12 red flags

Table 4

Table 5

Figure

Table 6

Table 7

Table 8

ICD-10 codes

Medical writing support provided by John Jesitus, MA

A common complaint among children and adolescents, headaches including migraines remain the top reason for referrals to pediatric neurology.^1,2 The worldwide prevalence of migraine in children and adolescents is 7.7%.³ Reported prevalence increases with age, from 3% (age 3 to 7 years) to 8% to 23% (age 11 to 15+ years).⁴ Approximately 10% of school-aged children suffer from migraine, with boys being more frequently affected before puberty, and girls more frequently thereafter.⁵ A comprehensive 2010 survey estimated that migraine has a global prevalence of 14.7%, making it the third-most-common disease in the world in men and women.⁶

All these headaches carry costs beyond their physical toll. On average, children with migraine miss 8 school days yearly, versus 4 for children without migraines.⁷ Among adults globally, migraine ranks seventh among specific causes of disability, and among the top 10 causes of disability in 14 of 21 world regions.⁸ One analysis reveals that between 2008 and 2013, patients with migraine had significantly higher direct and indirect healthcare costs ($10,363 and $11,294, respectively) than did patients without migraines ($4619 and $8945, respectively).⁹

Additionally, the migraine burden cannot be measured with dollars alone. Researchers have likened the impact of migraines on children's quality of life to that of arthritis, diabetes, and cancer.^10,11

Yet the seriousness of migraine remains underappreciated by parents, teachers, primary care providers,12 and often migraine sufferers themselves, most of whom are never diagnosed or treated.⁵ The psychosocial and economic burden of pediatric migraine, coupled with the relief offered by newer treatments including triptans, lends urgency to accurately identifying and promptly treating migraine.^2,12

Migraine classification

The considerable variability of migraine within and among patients stems from dysfunction of an ion channel in brainstem nuclei that normally modulates sensory input and regulates the meningeal blood vessels.¹³ Pathophysiologically, neural abnormalities drive dilation of cranial blood vessels, resulting in further nerve activation and pain.¹⁴

The International Classification of Headache Disorders, 3rd edition (ICHD-3), classifies headaches into primary, secondary, and those caused by cranial neuropathies and other headaches (Table 1).¹⁵

Primary headaches

This category includes diagnostic criteria for migraine and its variants, along with tension-type headache (TTH) and other trigeminal autonomic cephalalgias (TACs).

Migraines can occur with or without aura; specifically, at least 2 attacks that include 1 or more reversible visual, sensory, or other symptoms that meet specific temporal criteria.

Patients who have migraine without aura may experience prodromal symptoms up to 48 hours before other migraine symptoms. These symptoms may include:

·      Fatigue

·      Nausea

·      Difficulty concentrating

·      Stiffness

·      Photophobia/phonophobia

·      Blurred vision

·      Yawning

·      Pallor.

Additional types of primary headaches include TTH and TAC.

All forms of TTH typically involve a mild-to-moderate bilateral headache, pressing or tightening in quality. Increased pericranial tenderness is the most significant abnormal finding in patients with any type of TTH.¹⁵ Pain does not worsen with routine physical activity and may or may not be associated with nausea; phonophobia or photophobia may occur.

Finally, TACs are unilateral headaches, usually accompanied by prominent cranial parasympathetic autonomic features (such as conjunctival injection and/or lacrimation, nasal congestion, and facial sweating), which are lateralized and ipsilateral to the headache.¹⁵

Other primary headaches

Additional forms of primary headaches include the following (see ICHD-3 for descriptions and details¹⁵):

·      Cough

·      Exercise

·      Sexual activity-associated

·      Thunderclap

·      Cold stimulus

·      External-pressure

·      Stabbing

·      Nummular

·      Hypnic

·      New daily persistent headache (NDPH).

Secondary headaches

Secondary headaches include new headaches and preexisting or significantly worsening preexisting headaches caused by primary disorders such as trauma and systemic diseases.¹⁵ Other causes include:

·      Trauma or injury to head and/or neck

·      Cranial and/or cervical vascular disorder

·      Nonvascular intracranial disorder

·      Increased intracranial pressure

·      Substance or its withdrawal

·      Infection

·      Disorder of homeostasis

·      Psychiatric disorder

·      Headache or facial pain attributed to disorder of the cranium, neck, eyes, ears, nose, sinuses, teeth, mouth, or other facial/cranial structure.

Cranial neuropathies, centrofacial pain, and other headaches include painful cranial-nerve lesions and other facial pains deriving from a complex catalog of causes such as trigeminal, glossopharyngeal, occipital, and other neuralgias; optic neuritis; ischemic oculomotor nerve palsy; and various facial neuropathies and syndromes.¹⁵

Evaluation

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

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.

Triptans

Physicians typically reserve serotonin 5-HT_1B/1D receptor agonists (triptans; Table 5^22,26-30) 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-HT_1B/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 7^2,34).

Migraine prevention

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 8^12,22,37,38).

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:

·      Erenumab

·      Fremanezumab

·      Galcanezumab.

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.

References:

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2. O'Brien HL, Kabbouche MA, Hershey AD. Treatment of acute migraine in the pediatric population. Curr Treat Options Neurol. 2010;12(3):178-185.

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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.

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6. Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2163-2196. 

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33. Orlova Y, Rizzoli P, Loder E. Association of coprescription of triptan antimigraine drugs and selective serotonin reuptake inhibitor or selective norepinephrine reuptake inhibitor antidepressants with serotonin syndrome. JAMA Neurol. February 26, 2018. Epub ahead of print.

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35. Freitag FG, Schloemer F, Shumate D. Recent developments in the treatment of migraine in children and adolescents. Headache Pain Manag Case Rep. 2016;1:1.

36. Lipton RB, Bigal ME, Diamond M, et al; AMPP Advisory Group. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68(5):343-349.

37. Powers SW, Coffey CS, Chamberlin LA, et al; CHAMP Investigators. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med. 2017;376(2):115-124.

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.