Headaches are one of the most common health issues in childhood, with 60–75% of children reporting that they have had a significant headache by the age of 15. Approximately 1 in 10 children experience recurrent headaches due to migraine specifically. Pediatric migraines exert a substantial impact on the well-being of children, causing not only physical discomfort but also significantly impairing school performance and quality of life. Recognizing the multidimensional challenges faced by pediatric migraine sufferers, a patient-centered and holistic approach is important for effective management. Functional medicine creates tailored interventions to address the unique underlying factors of migraine for each child, fostering improved outcomes and enhanced quality of life.

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Comprehensive Understanding of Pediatric Migraines 

Migraine is the most frequent primary headache disorder in children and adolescents. While pounding or throbbing head pain is the most common symptom, pediatric migraine can manifest with other symptoms as well, including nausea, vomiting, abdominal pain, sensitivity to light and sound, dizziness, and lightheadedness. The variability in symptomatology poses diagnostic challenges, as some children may experience atypical manifestations, leading to potential misdiagnoses (55). Migraine is divided into six major categories, the two most important of which are migraine without aura and migraine with aura (74). 

A detailed history is important in the diagnostic process. The patient must have at least five attacks that fulfill the criteria of migraine:

• Headache lasting 1-72 hours
• Headache with 2 of the 4 qualities:

• Bilateral or unilateral (frontal/temporal) location
• Pulsating quality
• Moderate to severe in intensity
• Aggravated by activity

• At least one of the following:

• Nausea and/or vomiting
• Photophobia and phonophobia

The assessment will also include a physical examination, neurological examination, and potentially additional tests, like blood work or CT and MRI imaging, to eliminate potential secondary causes.

There is a significant genetic component to migraines, meaning if individuals have close family members, like parents or siblings, who suffer from migraines, there is an increased chance that they may also be prone to these headaches. Migraines can be activated by an environmental or physiological stimulus in genetically predisposed individuals. Commonly reported stimuli or triggers include stress, fatigue, various foods, alcohol, drugs, smoking, weather changes, and odors. 

The pathophysiology of migraine is still not completely understood. Migraine was historically considered a vascular disorder, but contemporary studies have shifted the perspective to view it as primarily a neurological condition. The neurogenic theory of migraine postulates that a genetically predisposed brain, when exposed to a migraine trigger, first undergoes changes in neurochemistry, such as changes to levels of serotonin, dopamine, and glutamate. This alteration in neurochemistry leads to the activation of the trigeminovascular system and the release of peptides, such as calcitonin gene-related peptide (CGRP), that trigger neuroinflammation (31, 61).

Recurrent headaches of any type can cause school problems, behavioral problems, and mood changes. Migraine in children is associated with school absences, impaired school performance, and other emotional and psychological disorders. In addition to the challenges faced by the children, parents frequently find themselves needing to take time off from work to care for their children dealing with migraine headaches (33, 63). 

Principles of Functional Medicine in Migraine Management 

Functional medicine is a patient-centered approach that aims to understand and address the underlying causes of health issues. At its core is the principle of systems biology, which views the body as an interconnected system where various components influence each other. This perspective is crucial in comprehending the complex nature of chronic conditions, like migraines, recognizing that multiple factors contribute to their development. 

In treating migraines in children, functional medicine utilizes advanced diagnostics to identify root causes, delving into genetic, environmental, and lifestyle factors. Understanding the genetic predisposition to migraines provides insights into an individual's susceptibility. Environmental factors, such as stress, diet, and exposure to certain substances, are examined to uncover triggers. Lifestyle elements like sleep patterns and physical activity are also considered.

Advanced Diagnostic Approaches for Pediatric Migraines

Advanced diagnostics allow functional medicine practitioners to dive more deeply into the possible underlying causes of migraine in children and provide personalized treatment plans. 

Genetic Polymorphisms

The MTHFR (methylenetetrahydrofolate reductase) polymorphism is a genetic variation that involves a specific gene, MTHFR, which plays a role in the metabolism of folate (vitamin B9) and methionine. This enzyme plays a key role in a complex biochemical pathway known as the methylation cycle. One of the primary functions of the MTHFR enzyme is to convert homocysteine, an amino acid, into methionine. This process is crucial for the synthesis of S-adenosylmethionine (SAMe), a methyl donor that participates in various biochemical reactions. MTHFR polymorphisms can result in a less efficient enzyme. Some studies have revealed an association between specific MTHFR gene variants, particularly the C677T variant, and an increased risk of migraine.

The Methylation Panel by Genova Diagnostics offers important insights into the methylation pathway, measuring both genetic polymorphisms as well as methylation metabolites. The test can uncover a patient's nutritional support needs, such as amino acids, vitamins, and minerals, in addition to understanding their genetic risk for less efficient methylation.

Gut Health

The gut-brain axis refers to the bidirectional communication that exists between the gastrointestinal tract and the central nervous system (CNS). This communication network relies on connections through the vagus nerve, hormones, and immune system mediators. Dysbiosis refers to an imbalance in the composition and function of the gut microbiome, the trillions of microorganisms residing in the digestive system. Research has demonstrated that alterations in the gut microbiota can influence the gut-brain axis, playing a role in the development of various neurological conditions (85). In the context of migraines, dysbiosis may contribute to inflammation and changes in the production of certain molecules that affect the nervous system, like neurotransmitters and short-chain fatty acids (SCFAs) (20, 42). Furthermore, imbalances in gut microbiota can lead to increased permeability of the intestinal barrier, allowing potentially harmful substances to enter the bloodstream. These substances may negatively impact the blood-brain barrier, leading to activation of immune cells in the brain and neuroinflammation (25, 46, 65). 

The GI Effects Comprehensive Profile by Genova Diagnostics is a stool test that provides insights into various aspects of gastrointestinal function, including the composition and metabolic activity of the microbiome, digestion, and inflammation. Cyrex’s Array 2 measures antibodies to components of the intestinal barrier, such as zonulin and tight junction proteins, or to lipopolysaccharide (LPS), a bacterial endotoxin. Elevations in these antibodies are a sign of intestinal permeability. Cyrex’s Array 20 can also be considered to assess for breaches in the blood-brain barrier.

Hormones

The prevalence of migraines increases during adolescence and, after puberty, occurs more frequently in females than males. Women of reproductive age are three times more likely to suffer from migraines than men (6). Fluctuations in estrogen levels can influence cellular excitability and cerebral vasculature, contributing to migraine susceptibility (71). Stress is also a trigger for 70% of migraine sufferers. Stress triggers a neuroendocrine response, activating the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis. These hormones can lead to changes in blood flow, immune function, and neurotransmitter levels, all of which may contribute to migraine susceptibility (73).

Genova’s Rhythm Plus test uses salivary measurements of estradiol, progesterone, and testosterone over 28 days to assess for hormone fluctuations throughout the monthly cycle. It also measures the diurnal rhythm of cortisol, to assess how the body is adapting to stress, and melatonin, a hormone produced by the pineal gland that is involved in regulating the sleep-wake cycle. Changes in sleep patterns or inadequate sleep can act as triggers for migraines in susceptible individuals.

The DUTCH Plus test by Precision Analytical is a comprehensive hormone test using dried urine. It measures metabolites of sex hormones, such as estradiol, progesterone, and testosterone, as well as adrenal hormones, like DHEA cortisol, and melatonin. It also includes markers related to oxidative stress, such as 8-hydroxy-2'-deoxyguanosine (8-OH-dg). Oxidative stress refers to an imbalance between the production of reactive oxygen species (ROS) and antioxidants in the body. It has been implicated in various headache disorders, including migraine (34). 

Environmental Exposures

Environmental exposures can play a role in triggering or exacerbating migraines for some individuals. Chemical intolerance or sensitivity refers to an increased reactivity to certain substances, including chemicals found in the environment. Environmental exposures may contribute to central sensitization, a process in which the central nervous system becomes more responsive to stimuli. Chemical sensitivity and central sensitization are seen in higher prevalence in patients diagnosed with migraine. In addition to chemical exposures, exposure to mold and mycotoxins, toxic substances produced by certain molds, has also been associated with neurological symptoms, including migraines (26, 27, 39, 70). 

The Environmental Pollutants Profile (EPP) by US Biotek measures 14 metabolites in the urine associated with toxins. The MycoTOX by Mosaic Diagnostics measures 11 different mycotoxins in the urine, targeting 40 different mold species.

Food Sensitivities

Foods are a well-documented trigger in the onset of migraine. In addition to specific dietary compounds, such as nitrates, known to trigger migraines, immune reactivity to certain food proteins might also play a role. Food sensitivities refer to immune reactions to proteins in certain foods. Unlike immediate allergic reactions involving immunoglobulin E (IgE) antibodies, IgG or IgA reactions are considered delayed sensitivity reactions occurring hours to days after the food is ingested. Consuming food sensitivities can trigger the immune system to release inflammatory substances, making susceptible individuals more prone to migraine attacks by influencing blood vessel function and neuronal excitability (32, 92).

Cyrex’s Array 10 - Multiple Food Immune Reactivity Screen measures IgG and IgA antibody responses to raw, cooked, and modified foods as well as food enzymes, lectins, and artificial food additives. Most food sensitivity tests only test against foods in their raw form, which can miss reactions to the food if it is cooked, modified, or combined with other ingredients.

Nutrients

Deficiencies of many nutrients, including magnesium, niacin (B3), riboflavin (B2), cobalamin (B12), coenzyme Q10 (CoQ10), carnitine, α-lipoic acid (ALA), and vitamin D, are associated with migraine (61). SpectraCell’s Micronutrient Test analyzes 31 vitamins, minerals, and other nutrients to assess for any insufficiencies. It measures the amounts of these nutrients in the white blood cells, instead of the serum, to evaluate the level of nutrients absorbed and utilized by cells.

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Nutritional and Dietary Modifications for Pediatric Migraines 

Specific foods like chocolate, cheese, nuts, citrus fruits, processed meats, monosodium glutamate, aspartame, fatty foods, coffee, and alcohol are commonly reported food triggers by individuals with migraines. Avoidance of these foods is often recommended to prevent headache onset, but this might not be effective for everyone. An elimination diet is the gold standard for diagnosing food sensitivities or intolerances. All potentially problematic foods or food ingredients/additives should be removed for several weeks. Individual foods are then reintroduced one at a time over a few days to see if any problematic symptoms arise. Any foods that provoke unwanted symptoms are then removed for a longer period before any attempts for reintroduction are made again. The goal of an elimination diet with reintroduction is to temporarily remove foods that promote immune system reactivity and inflammation. 

This enables patients to gradually transition back to a more nutritionally diverse diet, reducing the likelihood of nutrient deficiencies that can occur when adhering to a strict, long-term elimination diet. Ketogenic diets (KD) are low-carbohydrate, high-fat diets that induce a state of ketosis, in which the body shifts its primary source of energy from carbohydrates to fats. The KD has been used to treat neurological conditions and there is some evidence that it might be beneficial in the treatment of migraine through decreasing brain excitability, neuroinflammation, and oxidative stress (64, 89). Some evidence also suggests that anti-inflammatory diets, emphasizing fruits and vegetables, healthy fats, whole grains, and omega-3 fatty acids can aid in migraine treatment (60). 

Managing pediatric migraines through dietary interventions can be complex, and the effectiveness of specific dietary plans may vary among individuals. It's crucial to acknowledge that what works for one child may not work for another, and personalized guidance is essential. Furthermore, elimination-style diets can increase the risk of malnutrition. Consulting with a registered dietitian or nutritionist can be valuable in developing a safe and tailored nutrition protocol.

Supplements & Nutraceuticals 

There is growing interest in integrating the use of supplements and nutraceuticals into the management of pediatric migraine.

Magnesium

Magnesium deficiency influences cortical spreading depression, the release of proinflammatory neuropeptides, and vasoconstriction, contributing to migraine symptoms. Good food sources of magnesium include green leafy vegetables, legumes, nuts, seeds, and whole grains, but many children may struggle to obtain adequate amounts through diet alone. Magnesium supplements are available in diverse chelated forms, such as magnesium citrate, magnesium glycinate, and magnesium oxide. These formulations vary in their absorption rates and bioavailability, influencing their effectiveness in addressing magnesium deficiencies and associated health concerns. The American Headache Society recommends a dose of 400-500 milligrams a day of magnesium oxide (1, 61). 

Riboflavin

Low riboflavin can lead to mitochondrial dysfunction and may affect migraine pathogenesis. High-dose riboflavin supplements can reduce pediatric migraine duration and frequency. A commonly recommended dose is 400 milligrams a day (1, 61).

Herbal Treatments

While butterbur (Petasites hybridus) and feverfew (Tanacetum parthenium) have demonstrated efficacy in headache and migraine treatment for adults, their use is not recommended in pediatric migraine management. This precaution stems from limited research on the safety and efficacy of these herbal remedies in children and concerns about potential side effects. Thus, caution is advised, and it is essential to consult with healthcare professionals to explore age-appropriate and evidence-based approaches for pediatric migraine treatment (1, 41).

Mind-Body Therapies and Stress Reduction for Pediatric Migraines 

Mind-body therapies, such as biofeedback, yoga, and meditation, assist not only in stress reduction but also in migraine management. These practices promote a relaxation response, activating the parasympathetic nervous system (PNS) and mitigating the chronic stress-induced activation of the SNS and HPA axis. Integrative and complementary therapies implemented alongside conventional treatments may prevent medication overuse, optimize clinical outcomes, and provide patients with better treatment experiences that increase self-care and feelings of empowerment (28).

Biofeedback is a therapeutic technique that involves the use of electronic monitoring instruments to provide individuals with real-time information about autonomic, and physiological processes in the body such as respiratory rate, heart rate, muscle tension, brain wave activity, and skin temperature. With the feedback in mind, individuals are taught techniques to consciously influence or control the physiological process being measured. For example, if muscle tension is being monitored, the individual may learn relaxation techniques to reduce tension when it rises. Biofeedback has been shown to reduce pediatric migraine frequency. 

Mindfulness meditation is a practice wherein an individual is aware of current sensations and feelings without interpretation or judgment. Engaging in mindfulness includes techniques such as breathing exercises, guided imagery, and other practices aimed at inducing relaxation in both the body and mind, ultimately assisting in stress reduction. This type of practice is used routinely in the management of stress, anxiety, depression, insomnia, and pain. Adolescents with migraine who received mindfulness training reported reduced headache frequency, as well as positive changes in medication use and symptoms of depression and anxiety.

Improving Sleep Quality in Children with Migraines 

Migraines are linked to sleep disorders, as well as suboptimal sleep patterns characterized by either inadequate or excessive duration and poor quality. This connection between migraine and sleep problems may arise from dysfunction in common brain regions (57, 86).

Psychological interventions, such as cognitive-behavioral therapy (CBT), can be effective in managing sleep issues and reducing headache frequency in pediatric migraine patients by addressing psychological factors that contribute to or exacerbate the condition. CBT may include identifying and modifying negative thought patterns, managing stress, and improving coping strategies, which can positively impact sleep (76). 

Sleep hygiene involves adopting healthy sleep habits and practices to promote good quality sleep. Establishing a consistent sleep schedule, creating a conducive sleep environment, limiting screen time before bedtime, and practicing relaxation techniques can contribute to better sleep quality. Implementing these practices has been shown to lower the frequency and shorten the duration of migraine attacks in pediatric patients with migraine. 

Community Support and Education 

Migraines disrupt the daily lives of children and adolescents, affecting their home, school, and social activities. The repercussions of migraines extend beyond the attacks themselves, leading to a notable decline in the overall quality of life for young individuals. Individuals with migraines are more likely to experience comorbid conditions such as depression, anxiety, and behavioral challenges, distinguishing them from their peers with other headache types or those without headaches. Social and community support can play a crucial role in managing pediatric migraines and positively impacting the well-being of affected children. 

Dealing with chronic health conditions like migraines can be emotionally challenging for children. Children may feel isolated due to the unpredictable and sometimes misunderstood nature of their condition. Being part of a support group helps combat feelings of isolation, providing a sense of belonging and understanding. Community support should also facilitate education about migraines, helping peers, teachers, and community members understand the condition better. This awareness can reduce stigma, foster empathy, and create a more inclusive environment for the child. The impact of migraine on education is substantial, with it being among the top three causes of absenteeism in children. Management should include proper support from schools, including necessary accommodations to improve attendance and performance (7). 

Future Directions in Functional Medicine for Pediatric Migraines 

In recent years, there has been a growing interest in researching novel treatments and prevention strategies for pediatric migraines. The future of migraine care in children is marked by advancements in technology, including the potential of wearable devices for monitoring and managing migraines.

Research on CGRP inhibitors, a class of medications that target a neuropeptide involved in migraine pathways, has shown promise in reducing the frequency and severity of migraines. While these drugs are currently only approved for adults, ongoing studies are assessing their safety and efficacy in pediatric populations. Botulinum toxin, commonly known as Botox, is another prospective treatment for pediatric migraines. The mechanism of Botox in migraine treatment involves its ability to block the release of certain neurotransmitters and modulate pain pathways. In adults, Botox has been approved for chronic migraine treatment. While research on the use of Botox for pediatric migraines is still in its early stages, initial studies have shown encouraging results (40, 43).

Beyond pharmaceutical treatments, another innovative treatment approach involves neurostimulation. The mechanism behind these treatments is to stimulate parts of the nervous system to reduce migraine pain or frequency. Non-invasive neurostimulation devices, such as transcranial magnetic stimulation (TMS), non-invasive vagus nerve stimulation (nVNS), and remote electrical neuromodulation (REN), are wearable devices that provide stimulation without penetrating the skin (29, 59).

Wearable devices and machine learning hold significant potential in the realm of tracking and predicting migraine attacks, offering a proactive approach to migraine management. Wearable devices, such as smartwatches or fitness trackers, can be equipped with various sensors to monitor physiological parameters associated with migraines. These may include heart rate variability, skin conductance, sleep patterns, and physical activity levels. Some wearables can also capture environmental data, such as changes in temperature, humidity, or barometric pressure, which are known migraine triggers for some individuals. Users can manually input information about migraine triggers, symptoms, and medication usage through wearable apps, contributing to a more holistic dataset. By identifying subtle changes in physiological parameters or recognizing patterns associated with previous migraine onsets, machine learning algorithms can generate early warning signs. This allows individuals to take preventive measures or manage triggers before the onset of a full-blown migraine attack. Machine learning can analyze historical data to identify specific triggers for migraine attacks, helping individuals modify their behavior or environment to minimize the likelihood of future episodes (75).

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Managing Pediatric Migraines: Key Takeaways

A holistic, functional medicine approach in the management of pediatric migraine includes uncovering the unique root causes and triggers for each child. Discovering individuals’ unique needs allows for a comprehensive and tailored treatment plan, including both conventional and integrative therapies for optimal clinical outcomes. Fostering collaboration between families, healthcare providers, and educators is crucial in providing complete support for children affected by migraines.