Migraine in children and adolescents remains underrecognized and underdiagnosed due to challenges like nonspecific symptoms, poor articulation of symptoms from patients, and lack of awareness of the prevalence of migraine in these populations.1 Migraine affects up to 10% of children from the ages of 5 to 15 years and up to 28% of adolescents between 15 to 19 years old.2

Often disabling, migraine in these populations can lead to increased absence from school and place significant stress on the child and the entire family if not successfully identified and treated. An accurate diagnosis of migraine in children and adolescents relies on criteria similar to that used in diagnosing migraine in adults. The evaluation starts with distinguishing between the likelihood of a primary headache disorder vs a secondary headache disorder. Adequate workup and assessment are required before labeling the headache as a primary headache disorder. Early treatment is important because pediatric headache carries a high risk of developing into a chronic condition that persists into adulthood.3

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Aggressive, Preventive Interventions

Since migraine can vary in intensity among individuals, it is critical to assess its impact, as it will affect therapeutic decisions.4 Several available tools can be used to measure the impact. PedMIDAS is a tool that is can be used to evaluate intervention effects.

“Significant benefit” was found a priori in a study reviewing the efficacy of a unilateral greater occipital nerve infiltration (GONI), using a mixture of methylprednisolone acetate and lidocaine 2%.4 A decrease in headache frequency was noted for intensity and duration; follow-up data indicated that 62% of patients with chronic migraine (CM) benefited and 34% reported significant benefit for a mean duration of 5.4 weeks. However, the study authors commented that GONI is unlikely to be a long-term solution in the treatment of pediatric migraine, but it can be used as a short-term solution to “jump start” a child’s improvement while waiting for prophylactic treatments to become effective.5

Powers and colleagues conducted a large randomized, placebo-controlled trial to determine which medication can be used to prevent pediatric migraine.6 Between the groups of patients receiving amitriptyline, topiramate, and placebo, there were no significant between-group differences in the primary outcome of relative reduction of 50% or more in the number of headache days in the 28-day baseline period to the final 28-day period of a 24-week trial. There were also no significant between-group differences in headache-related disability or headache days. 4

More studies are urgently needed to find preventive therapeutic approaches for effectively treating CM and episodic migraine in children and adolescents. There are few available studies on treatment of pediatric CM. Medications used for CM prophylaxis, such as amitriptyline, topiramate, and divalproex, are routinely prescribed off-label, and they seem to be effective and safe, but clinicians may be observing the placebo effect that can be explained by beliefs and perceptions inherent to the age group.7

Cognitive Behavioral Therapy Approaches

In a systematic review of the efficacy of cognitive behavioral therapy for pediatric migraine, the meta-analysis revealed evidence that cognitive behavioral therapy is not only beneficial to children with migraine, it may also augment the efficacy of medications like amitriptyline.8 Kroner and colleagues found that children and adolescents receiving cognitive therapy plus amitriptyline were more likely to reach the clinically meaningful outcome of fewer than 4 headache days per month than children and adolescents who received headache education plus amitriptyline.9

Weight-Control and Nutritional Interventions

Obesity is a known risk factor for episodic and chronic pediatric migraine. Based on increasing evidence that migraines are a response to cerebral energy deficiency, several studies have aimed to investigate the ketogenic diet (KD) as a therapeutic intervention as a way to prevent migraines. Of the 3 ketone bodies that serve as energy substrates in the absence of dietary glucose, D-β-hydroxybutyrate has been shown to increase cerebral metabolism, glucose transport, and mitochondrial functioning while decreasing cerebral excitability and oxidative stress.10 Intervention with KD has been successful in decreasing seizure frequency in children with refractive epilepsy.

“Epilepsy and migraine are related — some epilepsy forms grow out into migraine,” said Elena Gross, University Children’s Hospital Basel, University of Basel, Basel, Switzerland, principal investigator on research involving ketogenic dietary intervention for neurological conditions. “Ketosis targets most mechanisms known to be involved in migraine.”

The clinical efficacy of very low-calorie ketogenic diet in a population of patients with migraine who are overweight was reported by Di Lorenzo and colleagues.11 The researchers evaluated the influence of 4 weeks of KD on habituation of visual and somatosensory cortical evoked potentials in patients with episodic migraine during the interictal phase. Based on their findings that KD could significantly normalize the habituations deficit on evoked potentials for the duration of migraine clinical features, the researchers speculated that induction of neural plasticity, changes in cortical excitability, and enhancement of energy metabolism could underlie these findings.

“Our exogenous ketone body trial is still running, but I would consider the evidence for a benefit of ketosis in migraine as fairly robust and a much safer option (if done correctly) as any of the pharmacological agents we have,” continued Dr Gross. “Especially since they don’t work well on kids.”

References

1. Qureshi MH, Esper GJ, Bashir FF. When to consider prophylactic antimigraine therapy in children with migraine. Curr Treat Options Neurol. 2019;21(4):15.

2. Kacperski J, Bazarsky A. New developments in the prophylactic drug treatment of pediatric migraine: what is new in 2017 and where does it leave us? Curr Pain Headache Rep. 2017;21(8):38.

3. Moscano F, Guiducci M, Maltoni L, et al. An observational study of fixed-dose tanacetum parthenium nutraceutical preparation for prophylaxis of pediatric headache. Ital J Pediatr. 2019;45(1):36.

4. Arruda MA, Chevis CF, Bigal ME. Recent advances in the management of chronic migraine in children. Expert Rev Neurother. 2018;28(3):231-239.

5. Gelfand AA, Reider AC, Goadsby PJ. Outcomes of greater occipital nerve injections in pediatric patients with chronic primary headache disorders. Pediatr Neurol. 2014;50:135-139.

6. Powers SW, Coffey CS, Chamberlin LA, et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med. 2017;376:115–124.

7. Arruda MA. No evidence of efficacy or evidence of no efficacy. JAMA Pediatr. 2013;167:300-302.

8. Ng QX, Venkatanarayanan N, Kumar L. A systematic review and meta-analysis of the efficacy of cognitive behavioral therapy for the management of pediatric migraine. Headache. 2017;57(3):349-362.

9. Kroner JW, Hershey AD, Kashikar-Zuck SM, et al. Cognitive behavioral therapy plus amitriptyline for children and adolescents with chronic migraine reduces headache days to ≤4 per month. Headache. 2016;56(4):711-716.

10. Gross EC, Klement RJ, Schoenen J, D’Agostino DP, Fischer D. Potential protective mechanisms of ketone bodies in migraine prevention. Nutrients. 2019;11(4):E811.

11. Di Lorenzo C, Coppola G, Bracaglia M, et al. Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: a multimodal evoked potentials study [published online May 31, 2016]. J Headache Pain. doi: 10.1186/s10194-016-0540-9