Tuesday, June 6, 2023

Migraine in children and adolescents


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...

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. 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.

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. It is important to distinguish BPT from the more common typical torticollis of infancy and Sandifer syndrome.

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. 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.

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.

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. 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.

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. 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...


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. 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.

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. Nutraceuticals such as riboflavin, magnesium, and coenzyme Q10 have low-risk profiles 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, 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.

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...


Available evidence24 supports the use of a combined pharmacotherapy and behavioral approach for migraine prevention in children and adolescents. 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.

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.


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.
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.

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.  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.


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.

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