Migraine in Children

Headache Classification for Children

The 2018 International Classification of Headache Disorders, 3rd edition (ICHD-3) has different requirements for migraine diagnosis in children and adolescents (age < 18 years) as compared with adults.¹ In the case presented (Box 1), our patient Harper’s symptoms would not meet the established classification of episodic migraine without aura for adults, but do meet the modified criteria for children (Box 2).

The duration of an attack must be between 2 and 72 hours, which is a change from the previous edition, which required only a 1-hour minimum duration. Adults are required to have a 4-hour minimum duration. It is important to highlight that if a child sleeps during migraine, the time spent sleeping is included in the length of the attack. For Harper, that means 30 minutes of headache plus 2 hours of sleep is an attack lasting 2.5 hours. Other differences between migraine in children and in adults include that photophobia and phonophobia may be inferred from behaviors (eg, blocking out the light under a blanket or telling others to be quiet) and bilateral location is acceptable because this is often seen in children.

Also new to the ICHD-3 is that infantile colic is a proposed episodic syndrome that may be associated with migraine. Infantile colic occurs in 5% to 19% of infants and affects boys and girls with about the same frequency. The cause of infantile colic still remains poorly understood despite research into various gastrointestinal etiologies. Infantile colic has a significant impact on health because it is associated with reduced breastfeeding, maternal depression, and shaken baby syndrome (Box 3).

Parents with migraine are 2 (men) to 2.5 (women) times more likely to have infants with colic compared with parents who do not have migraine.² A meta-analysis showed that infant colic was associated with increased odds of migraine.³ Further research is needed to determine if formal classification as a migraine-related phenomenon and treatment with migraine medications is warranted for babies with infantile colic.

Occipital Location—Still a Red Flag?

Many practicing neurologists learned that a primary occipital location for headache in a child should raise the level of suspicion for secondary headache due to intracranial lesion and this is still included in the ICHD-3.¹ This information was based on a study of children presenting to the emergency department with headache in which the number of children who reported occipital headache was very small. In this study, individuals with occipital headache and intracranial lesions had other objective signs from their neurologic examination.^4,5 A more recent retrospective study of 308 patient charts, however, showed that children with occipital headache alone (7%) or as some component of their headache (14%) were not more likely to have significant intracranial pathology on imaging than other children with headache in other locations. The authors concluded that in the absence of other concerning history or abnormal findings from a neurologic examination, neuroimaging could be deferred for most children with occipital pain.⁶ In a prospective study of 314 pediatric participants, 39 (12%) had occipital headaches that most commonly were caused, not by intracranial lesions, but by viral syndromes and primary headaches disorders, such as migraine.⁷

Treating Migraine in Children

The impact of migraine can be substantial to children and their families, resulting in many missed school days for the child and missed work days for the child’s caregivers.

Cognitive Behavioral Therapy

Medication and lifestyle change alone do not provide headache control for a large population of children with chronic headache. Several small trials demonstrated efficacy for cognitive behavioral therapy (CBT) in children with migraine.⁸ In a large study, 135 children with chronic migraine were randomly assigned to receive 2 interventions of 10-week sessions of either CBT and amitriptyline or headache education and amitriptyline. After 20 weeks, there was a significant reduction in headache days for the participants who received CBT compared with those who received headache education. Participants who had CBT also had significantly greater reductions in Pediatric Migraine Disability Assessment (PedMIDAS) scores.⁹ Subsequent analyses demonstrated that children who participated had good adherence¹⁰; however, of 398 children screened for participation, 57% refused to participate.⁹ Further supporting a role for CBT for children with migraine, a meta-analysis of 14 studies showed significant clinical improvement (reduction of headache by 50% or more) with CBT after 3 months that was maintained for up to 12 months.⁸

Unfortunately, there are barriers to accessing CBT for many children with headache or chronic pain, including availability of adequately trained providers, mental health insurance coverage, family availability, and willingness to participate.^11-13 Attempts have been made to circumvent the barrier of availability by using telemedicine and internet-based interventions. A pilot randomized controlled trial of internet-delivered CBT for children failed to demonstrate a clinically significant benefit for this approach.¹⁴ A meta-analysis on internet-delivered CBT for chronic pain in children and adolescents showed that individuals improved in several areas compared with their pretreatment baseline; however, this improvement was not statistically significant. In this analysis, only parental protective behaviors significantly improved for children treated with CBT compared with participants in the control group.¹² Further research is needed in this area, and there is a significant role for physician advocacy that may lead to greater access to CBT.

Pharmacologic Treatment

Research regarding commonly used abortive and daily preventive treatments in children is limited. Most studies are small and not designed to compare medications to each other. As a result, there are only a few medications that are approved by the Food and Drug Administration (FDA) for treatment of migraine in children (Table 1). Practice guidelines for preventive and acute treatment of migraine in children are being developed by the American Academy of Neurology.

The CHAMP study^a was the first large study to evaluate commonly used daily migraine treatment options for children with migraine.¹⁵ In this multicenter randomized double-blind placebo-controlled trial, amitriptyline (1 mg/kg/day), topiramate (2 mg/kg/day) or placebo were given to children ages 8 to 17 years. All 3 groups of participants, including those given placebo, had similar rates of improvement over a 6-month period and the study was terminated early for futility. No difference between younger and older participants was observed. A higher rate of side effects occurred in participants treated with topiramate. Future research may focus on individuals’ genetics or other coexisting conditions that may affect which children are medication responders.

There are no daily preventive medications that have FDA-approved indications for treating migraine in children under age 12 years. The serotonin and histamine antagonist, cyproheptadine (which also has anticholinergic effects) is among the more commonly prescribed daily preventive medications for children under age 12 years, although use for this indication in this age group is not FDA-approved.

When selecting abortive medication, it is important to discuss if the child has learned to swallow pills or if they are unable to swallow pills during a migraine, because of symptoms such as vomiting. Many medications are available in nonoral formulations (Table 2). Triptans can be used safely to treat children and adolescents. General practice recommendations are to start at the lowest dosing option available.

Rescue medication effectiveness can be optimized by making sure the child takes medicine as close to the start of a headache as possible, which requires having access to the medicine at school. Many schools require medication administration forms and creating a patient-specific migraine action plan can be helpful. An action plan can be used at home and school and should include advice regarding when to seek out emergency care.^16,17 For families who are concerned about medication side effects, a medication trial can be done at home even in the absence of a headache to monitor for side effects before it is used in a school setting.

Monoclonal antibodies (MAbs) to calcitonin gene-related peptide (CGRP) or its receptor have recently been FDA-approved for treatment of migraine and cluster headache in adults.¹⁸ As these are an effective option with a novel mechanism, it will be important to assess safety and efficacy of the CGRP MAbs for children with headache. This process has begun but may take years to deliver definitive results. In the meantime, an expert consensus document was published by the Pediatric and Adolescent Headache special interest section of the American Headache Society, providing guidance on pitfalls prescribers should be aware of until more definitive data becomes available. All MAbs carry a risk of immunogenicity triggering anaphylaxis or more mild allergic reactions. Among the most important issues, unique to CGRP and children, are interactions in the central nervous system that may affect brain development, and potential effects on bone growth, weight, immune function, and cardiovascular health.¹⁹ There is a high placebo responder rate among children with migraine¹⁵ and in response to injections compared with pills.^20,21 The expert consensus is that these treatments should be reserved for postpubertal adolescents experiencing high migraine frequency and migraine-related disability with only rare exceptions.

Neuromodulation

Neuromodulation has become available as a nonpharm-acologic alternative to treat or prevent pain. These devices can be used alone or in combination with other treatments to avoid drug interactions or side effects common to medication treatments.²² Single-pulse transcranial magnetic stimulation (sTMS) is the only neuromodulation device approved for the acute and preventive treatment of migraine in adolescents age 12 years and up.

For 850 children across 28 studies, single- or paired-pulse TMS for any indication (eg, epilepsy, depression, or in a healthy control participant) did not cause seizures or other adverse events.²³ Magnetic field strengths generated by TMS devices are similar to the field strength of MRI scans, 1.5 to 2.0 T. The sTMS device generates a noise thought to be similar or less than what a child might experience listening to music or from environmental exposures (100-120 dB).

In a study of sTMS for treatment of migraine in adolescents age 12 to 17 years, sTMS was used to prevent or abort migraine. Initially, participants were asked to give 2 pulses, wait 15 minutes, and then give an additional 2 pulses twice daily. In this small study, 19 of 21 participants who enrolled completed a baseline assessment, and 12 children completed the study. Using sTMS proved feasible in this age group and acceptable with overall high compliance once treatment administration was streamlined. The 15-minute delay proved challenging for this age group, however, particularly on school days and was dropped. Study completion rate went from 31% (4/13) to 88% (7/8) once this change was made (P = .024). Importantly, there were no serious adverse events and only 2 participants reported mild discomfort.²⁴

Conclusion

Headache is common in children and adolescents, and most often is reflective of a primary headache disorder such as migraine. The exciting developments in diagnosis, classification, and treatment options will continue to help our younger patients. Helping children gain consistent access to therapies, notably CBT, is a worthy goal. Newer therapies that have shown promise in adults will continue to move rapidly into clinical practice with and without FDA approval, and it will require constant vigilance to be aware of the unique ways in which these may affect this population.