Migraine in Children and Adolescents

Headaches constitute the third most common cause of pediatric emergency department visits. Over the past 3 decades, the incidence of childhood migraine has increased. Childhood migraines may be episodic or chronic and are not associated with an acute self-limiting condition. Typical onset is during early to mid-adolescence, although migraine can begin at any age. Those who experience migraine at a younger age often continue to experience migraines into adulthood.¹

The differences in migraines between adults and children exist in clinical presentation, context of disability, efficacy, and safety of current treatments. Migraine often leads to substantial levels of functional disability in home, school, and social settings. Children with migraines have worse academic performance and increased risk of depression than their healthy same-aged peers.¹

Epidemiology

Migraine is a primary headache disorder affecting up to 7 million children and adolescents in the United States. Globally, nearly 60% of children and adolescents experience significant headache, and 7.7% to 9.1% have migraine.^2,3 Migraines affect female children and adolescents disproportionately, and disease prevalence increases over the course of development.⁴

Clinical Features

The main characteristic of migraine in children is moderate to severe pulsating pain that is unilateral or bilateral and affects the front or sides of the head (Table 1). Children may describe the headache as “their heart beating in their head”. Episodes can last for 2 to 72 hours and often improve with sleep.⁵

Migraines can occur with or without aura. Approximately one-third of older children and adolescents have an aura⁶ that includes visual, sensory, speech or language disturbances and motor or brainstem changes, manifesting as scotomas, paresthesias, dysphagia, hemiplegia, ataxia, or confusion.⁷ Some children experience auras as Alice in Wonderland syndrome, with objects appearing too small or large, too tall or short, too fat or thin, or too far away or too close.⁸

Hemiplegic migraine is a rare migraine subtype with aura symptoms involving motor weakness or numbness.⁹ Hemiplegic migraine presents at a mean age of 12 years with episodic attacks of reversible hemiparesis or hemiplegia lasting from hours to days, followed by headache. The headache is often contralateral to the focal deficits, whereas sensory disturbances typically are ipsilateral.¹⁰

Clinical Evaluation

Children should be given an overview of what to expect during the examination. It can be helpful to provide paper and crayons so children can draw a picture of how they feel when they get a headache, as drawings with migraine features have high concordance with migraine diagnosis (Figure 1).²

Teenagers can be questioned directly by the health care provider, with parents or guardians providing additional details as needed. Patients and families should be asked about adverse experiences in childhood, such as depression or bullying,¹¹ which can predispose individuals to headaches in childhood and later in life. Teenagers should be able to talk with the provider privately, away from the parent or guardian, to discuss safety, sexuality, and substance use.²

Initial imaging studies usually are not appropriate for evaluation of primary headaches in children. Imaging should be performed only in children with red flags in their history, such as early morning headache with vomiting, worsening headache symptoms, worsening of headache when supine, pain with Valsalva maneuver, rapid onset, mental status changes, or abnormal findings on physical examination. When neuroimaging is indicated, MRI is preferred over CT, because of exposure to ionizing radiation from the latter.¹²

Periodic Syndromes Related to Migraine

Migraines in childhood may not always present as headache. There are several episodic syndromes in children that are believed to be “migraine variants” but remain underdiagnosed because of inadequate recognition of these disorders. They occur at a younger age and may be migraine precursors in the developing brain.² Periodic syndromes typically vary with age at presentation and can occur as early as infancy. These migraine equivalents have similar characteristics despite their heterogenous presentation, including periodic nature, hereditary component, family history of migraine, evolution of the clinical picture to classic types of migraine, and no prominent headache in the symptomatology.¹³

Benign paroxysmal torticollis (BPT) is the rarest of the 4 periodic syndromes and the earliest in onset, occurring in the first 2 years of life.⁹ BPT is characterized by spontaneous, recurrent head tilting in infants and toddlers. Episodes typically last for a few days at a time and resolve by 3 years of age. Accompanying symptoms can include vomiting, irritability, vertigo, ataxia, and pallor.¹⁴ It is important to distinguish BPT from the more common typical torticollis of infancy and Sandifer syndrome.⁹

Toddlers and school-age children may present with paroxysmal vertigo, cyclic vomiting, and abdominal migraine. Benign paroxysmal vertigo (BPV) is an event characterized by vertigo, nystagmus, and vomiting that can last minutes to hours with spontaneous resolution.¹³ BPV presents abruptly, with or without accompanying pallor or fearfulness. Onset is typically early, between 2 and 5 years of age. Treatment includes rest, reassurance, and hydration. Differential diagnosis includes vestibular dysfunction following an ear infection or postinfectious inflammation of the vestibular nerve. These episodes also may elicit concern for posterior fossa lesion, focal onset seizure, or postictal behavior.⁹

Cyclic vomiting syndrome (CVS) comprises recurrent attacks of vomiting and nausea, lasting from 1 hour to 5 days, that are associated with pallor and lethargy. There is complete symptom resolution between attacks. The average age at onset is 5 years. Children often are able to identify triggers, such as foods, stress, or illness. Lifestyle measures such as adequate sleep and hydration are recommended for episode prevention. When making a CVS diagnosis, it is important to rule out an underlying gastrointestinal, metabolic, or mitochondrial disorder.⁹

Abdominal migraine represents 4% to 15% of pediatric gastroenterology cases, is more common in those with a migraine family history, and rarely persists into adulthood.¹³ Pain is dull, midline or periumbilical, and moderate to severe in intensity, lasting 2 to 72 hours if not treated. Headache is not a prominent feature; vasomotor symptoms, such as nausea, vomiting, pallor, and anorexia, are common. Up to 70% of children with abdominal migraine will develop more traditional migraine later in life, typically at 9 to 10 years of age.⁹

Adolescents may present with acute confusional migraines, characterized by agitation and pronounced memory disturbance. Symptoms can last up to 8 hours. Headache is not an important symptom and usually is not recognized during the acute attack.¹³ Headaches precede, accompany, or follow the acute confusional state in about 80% of patients. Neurologic examination reveals no focal signs during the attack and is obligatorily normal afterward. Attacks are usually relieved by sleep. Acute confusional migraines can be triggered by mild head trauma, leading to a false diagnosis of cerebral concussion. Metabolic and toxic encephalopathies, endocrine disturbances, infection, posterior fossa tumors, nonconvulsive status epilepticus, and stroke can present like acute confusional migraines. Therefore, although the diagnosis of acute confusional migraines is clinical, it is often a diagnosis of exclusion.⁹

Treatment

Once migraine has been diagnosed, the cornerstone of treatment is optimal rescue medication for acute attacks, initiation of migraine prophylaxis if indicated, and appropriate lifestyle modifications.

Rescue Medication

The purpose of acute migraine treatment is to improve pain and associated symptoms to facilitate a return to typical functioning as quickly as possible. Current evidence supports use of nonsteroidal anti-inflammatory drugs such as ibuprofen or acetaminophen as an initial treatment for children and adolescents with an acute attack. Triptans also are efficacious and are used if there is no response to initial treatment agents. Rizatriptan is the only Food and Drug Administration (FDA)–approved triptan for use in children 6 years of age or older.⁴ Other triptans, such as sumatriptan, zolmitriptan, and almotriptan, are approved for children aged 12 and above. Adolescents receiving oral sumatriptan/naproxen and zolmitriptan nasal spray are more likely to be headache-free at 2 hours than those receiving placebo. A study has shown that combination therapy such as sumatriptan/naproxen is well-tolerated and effective in adolescents, with no serious adverse effects.^6,15

Prophylaxis

The general principles of migraine prophylaxis are to reduce attack frequency, severity, and duration; improve responsiveness to treatment of acute attacks; improve function; and reduce disability.¹⁶ Using these guidelines can help provide a rationale for the institution of prophylaxis, such as in recurring migraines that cause daily disability, despite acute treatment; when frequency of attacks is greater than 4 per month; or a person has a contraindication to or has failed or overused acute therapies, has had adverse effects with acute therapies, or has an uncommon migraine condition, such as hemiplegic migraine.¹⁶ In recommending preventive measures, there are multiple modalities to consider (Table 2), including lifestyle changes, pharmaceuticals, behavioral therapies, nutraceuticals, onabotulinumA toxin, and neurostimulators.

Lifestyle Changes

Poor sleep, inadequate hydration, inactivity, and skipping breakfast are associated with increased likelihood of headache in adolescents.^2,4 Many studies also show a relationship between obesity and pediatric migraine, including a reduced migraine burden with weight loss.¹⁷ Obesity is a risk factor for progression from episodic to chronic migraine.¹⁸

Pediatric and adolescent patients should have water intake goals, engage in some form of exercise 3 days per week,¹⁸ and receive sleep guidelines tailored to their developmental stage.⁴

Nutraceuticals

When patients are hesitant to use pharmaceuticals for migraine prevention, there is evidence that nutraceuticals such as riboflavin or magnesium can be alternatives. One randomized controlled trial evaluated 98 adolescents with migraine treatment with riboflavin 400 mg vs placebo for 12 weeks and found improvement in headache frequency, duration, and disability scores.¹⁹ Another study compared the response to ibuprofen or acetaminophen taken acutely for migraine over an 18-month period in children and adolescents on 400 mg magnesium daily versus controls who were not on magnesium. Pretreatment with magnesium reduced pain intensity acutely when combined with acetaminophen or ibuprofen (P<.01) and resulted in reduced migraine frequency.²⁰

A nutraceutical also may improve the results of migraine prevention medications. Two different studies showed that supplementation with vitamin D increased the efficacy of both amitriptyline and topiramate in migraine prevention.²¹ Nutraceuticals such as riboflavin, magnesium, and coenzyme Q10 have low-risk profiles²¹ and may represent suitable first-line treatments, especially for patients who prefer not to take prescription medication.

Pharmaceuticals for Prevention

Pharmaceuticals for prevention of pediatric migraine include topiramate, propranolol, and amitriptyline. Topiramate is the only FDA-approved medication for migraine prevention in those aged 12 to 17 years. Per the current pediatric migraine prevention guidelines from the American Academy of Neurology and American Headache Society,²² individuals taking topiramate at a dose of 100 mg/day or 2 to 3 mg/kg/d are more likely than those taking placebo to have a reduction in the frequency of migraine or headaches. Per the same guidelines, children with migraine receiving propranolol at a dose of 20 to 40 mg 3 times a day may be more likely than those receiving placebo to have at least a 50% reduction in headache attacks. Amitriptyline was found to decrease frequency of headache days and migraine-related disability, but only when combined with cognitive-behavioral therapy.

The CHAMP study (Childhood and Adolescent Migraine Prevention) aimed to identify an optimal first-line migraine preventative treatment for people aged 8 to 17 years. The study concluded that amitriptyline and topiramate did not work better than placebo and had more adverse effects. These study results, however, may not be applicable to the population of children and adolescents excluded from the study, namely those who have continuous headache, medication overuse, or a high degree of migraine-related disability.²³

Achieving clinically meaningful improvement should be the standard for assessing the efficacy of a given treatment. Involvement of patients and their parents in determining what meaningful improvement means to them can improve understanding and adherence. Comorbidities should help guide the treatment. Individuals with mood disorder may benefit from a trial of amitriptyline. Obese patients may benefit from a trial of topiramate, which is an appetite suppressor.²²

Therapies

Available evidence²⁴ supports the use of a combined pharmacotherapy and behavioral approach for migraine prevention in children and adolescents.⁴ Psychologic treatments, such as cognitive-behavioral therapy, should be considered, either as first-line treatment or in combination with pharmaceutical-based therapies. Psychologic treatments delivered in a face-to-face format are effective in reducing pain and disability in children and adolescents with headache, with therapeutic gains maintained across time.¹

OnabotulinumA toxin

Although onabotulinumA toxin did not gain FDA approval for migraine treatment in those under age 18 after failing to show greater efficacy than placebo, a later crossover trial of onabotulinumA toxin for treatment of youth with chronic migraine showed that, compared with a placebo, children and adolescents who received a trial of onabotulinumA toxin injections administered in 3-month intervals and 6-week follow-up visits demonstrated a statistically significant decrease in migraine frequency and intensity.⁴

Neurostimulators

A recent open-label study²⁵ examined the safety, tolerability, and efficacy of a remote electrical neuromodulation device for treatment of acute migraine attacks among adolescents with migraine. Results showed that 71% of the participants experienced pain relief and 35% achieved pain freedom within 2 hours of symptom onset. Sustained pain relief was demonstrated among 90% of the participants at 24 hours. These preliminary data resulted in FDA clearance of the neuromodulation device for use among adolescents for acute treatment of migraine.⁴

On the Horizon

For children and adolescents who have failed other treatments, monoclonal antibodies that target the calcitonin gene-related peptide may be an option. Calcitonin gene-related peptide is an amino acid peptide found in sensory fibers in the central nervous system that is involved in processing and pain modulation and has been implicated in the pathophysiology of migraine. In adults, antagonism of this pathway has been associated with diminished headache days and medication usage.⁴

Anti–calcitonin gene-related peptide monoclonal antibodies are not currently FDA-approved for the treatment of migraines in people younger than 18.¹⁸ Several randomized controlled trials in children and adolescents with episodic and chronic migraine are underway.⁴ A special interest group of the American Headache Society for use of anti–calcitonin gene-related peptide monoclonal antibodies in children²⁴ recommends these medications for postpubertal adolescents experiencing frequent migraines with moderate or severe migraine-related disability. Individuals should have had adequate trials of established migraine preventive therapies, and previous options should have been expanded beyond prescription preventive medications to include, but not require, cognitive-behavioral therapy, as well as treatments with fewer side effects, such as neuromodulation devices and supplements.

Given the need to weigh potential benefits of therapy with unknown risks, an initial 2-month trial at the lowest available dose is recommended. If there is no improvement, a higher dose may be tried for another 2 months. If there is still no improvement, or if medication is not tolerated, it should be stopped.²⁴

Conclusion

Migraines present differently in young people than they do in adults, and children and adolescents require a different approach than their adult counterparts in all aspects of the clinic visit, from taking a history to providing treatment options. Episodic syndromes are migraine variants that may benefit from migraine treatment even if they do not present with a headache. The health care provider must understand the role of therapies such as cognitive-behavioral therapy in helping young patients manage headache pain, and to consider these therapies not only as adjunctive treatment but also as first-line treatment for the management of migraines in children and adolescents.