Introduction

☆ Editor’s note: In these conditions, a baby or older child will present with a set of recurrent symptoms and then may eventually have migraine when older. Sadly, diagnosis is often delayed because we are not smart enough to think about these entities. This causes undue distress for families as their child has recurrent bouts of pain and disability. Making the diagnosis earlier provides a great source of comfort and makes the provider a superhero!

Infant colic

All babies cry. Some babies cry more than others. When a healthy and well-fed infant cries excessively, it is referred to as “colic.” Approximately, 5%–19% of infants have colic. Crying follows a developmental pattern. Infants generally cry little during the first couple weeks of life. Crying increases around 2 weeks of life, peaks around 5 to 6 weeks of life, then tapers down by 3 months of age. Infant crying also follows a circadian pattern, with more crying in the late afternoon or evening hours. Infant colic may be an amplified version of this normal crying pattern; the infants cry more, and often inconsolably. Inconsolable crying is associated with caregiver frustration and, tragically, shaken baby syndrome—a form of child abuse. For decades infant colic was thought to be due to abdominal pain—either gas or something related to feeding- but those theories don’t necessarily fit. All that is clear is that the baby is in distress. It is impossible to know whether from pain or from something else.

A link between migraine and infant colic has been noted now in a number of studies. Children with migraine are more likely to have been colicky as infants. Children with tension-type headache are not. In a prospective, population-based cohort study, infant colic was associated with a more than 2 × increase in likelihood of migraine without aura by age 18. Mothers with migraine are more likely to have babies with colic, though fathers with migraine are not.

What might explain this link between migraine and infant colic? Remember that migraine is a disorder of amplified or distorted sensory processing, and migraine has a strong genetic link. Perhaps babies who inherit migraine genes experience the world differently than those who do not. The new stimuli they encounter in the world may be perceived in an amplified way in their brains. After a long day of amplified stimulation, the infants may express feeling overwhelmed through prolonged crying. If this is the case, then decreasing stimulation around the infant may be helpful. There is some evidence that advising parents to turn down the lights and avoid noisy toys may help with colicky crying. Around the age of 3 months, the infant’s brain starts to produce melatonin in a circadian pattern and they can begin to consolidate nighttime sleep. Sleeping for longer stretches may help colicky infants recover from stimulation during the day, leading to less crying around this age. Clearly there is much more to be understood about infant crying in general. However, excessive, fussy crying may be how migraine (read as “excessive sensitivity to stimuli,” not headache) looks in the young infant brain.

Benign paroxysmal torticollis (BPT)

This disorder typically starts during the first 6 months of infancy and resolves by pre-school age. It is characterized by recurrent episodes of head-tilt (i.e., torticollis), accompanied by irritability, fussing, pallor, and/or nausea/vomiting. Episodes may last for hours to days. The other symptoms may resolve while the head-tilt continues for a longer time. Once the child is old enough to crawl or walk, ataxia (wobbly walking) during episodes may become apparent as well. Attacks usually come at regular intervals. For example, a child may experience an attack every 6 weeks. However, the episodes tend to space further apart as the child ages.

Many children with BPT will have a family history of migraine. Children with BPT may be more likely to develop migraine than other children. This is especially true in children with BPT who have features of migraine—sensitivity to light, sound, or movement—during their attacks. (This may be how migraine looks in the young, developing brain). In some cases, a gene associated with familial hemiplegic migraine (CACNA1A) has been seen in infants with BPT.

As BPT is rare, there is limited information about how to treat it. Given the young age of the children, many families may not be interested in a daily preventive medication. Diagnosing BPT and explaining what to expect over time is often adequate. When nausea/vomiting is severe, acute treatment with an anti-nausea medicine may be reasonable.

While called “benign,” children with BPT may experience developmental delay. Most often seen is gross motor delay, but delays in other areas have also been reported. It is possible that spending several days a month experiencing a head-tilt makes it harder to progress in gross motor development, rather than delay being indicative of an underlying problem per se. Notably, once the episodes resolve, many of the children do catch up developmentally. There can be an impact on the family as well. As BPT is rare, many pediatricians are not familiar with it and there is commonly a delay in diagnosis. In one study, only 2.4% of pediatricians were aware of BPT. The diagnostic delay and associated testing can be stressful and anxiety-provoking for parents. Parents may also worry about triggering an attack, or about delays in their child’s development or their ability to engage in “normal” childhood activities. In one study, Infant Toddler Quality of Life scale scores helped to quantify the impact of BPT on infants and their families. Some children with BPT may go on to develop benign paroxysmal vertigo.

Benign paroxysmal vertigo (BPV)

While most migrainous phenomena lasts for hours to days, BPV attacks most commonly last for just a few minutes. BPV occurs predominantly in preschool aged children and is one of the more common causes of vertigo in young children. In BPV, attacks of vertigo come “out of the blue”; the child may suddenly appear scared or fall down to the ground. There may be accompanying nystagmus, and epilepsy is on the differential. Attacks usually last for less than 5 min, though they can go for longer. Typically, children outgrow BPT after a few years, but like the other disorders, it can persist. There is often a family history of migraine and children with BPV are more likely to grow up to have migraine.

As attacks are so brief, acute and preventive treatments are not usually needed. If the attacks are occurring multiple times a day, migraine preventive treatment could be considered. In this instance however, often video telemetry would be needed first to rule out epilepsy.

Abdominal migraine

Abdominal migraine involves repeated attacks of abdominal pain. The abdominal pain tends to be all over the belly or periumbilical (i.e., around the “belly button”). The pain feels dull or “just sore.” Other symptoms include nausea, vomiting, feeling unwell, looking pale, and/or not wanting to eat. Migrainous symptoms, such as sensitivity to light or sound, may be present. School-aged children are most often affected, though abdominal migraine can also occur in adults. There is often a family history of migraine. Those with abdominal migraine are more likely to go on to develop migraine (i.e., the headache form) once they grow older. The author has also seen children who describe typical visual migraine aura preceding attacks of abdominal migraine.

Even though children localize the pain to their abdomens, it is not clear that anything pathological is occurring in that area. It may be that thalamic processing develops over time, and what is perceived as “abdominal” pain in the young brain will later be perceived as “head” pain in the older brain. While ICHD-3 specifies that if headache is present during attacks, the diagnosis to consider is migraine rather than abdominal migraine, this author has found it hard to draw a distinct line where children cross from one diagnosis to another. It is not unusual to see a child who at age 7 describes attacks of abdominal pain, then by age 10, attacks include both abdominal and head pain, and then by age 12 or 13, attacks are described as headache and the abdomen is no longer mentioned. Calcitonin gene-related peptide (CGRP) is expressed in the gastrointestinal tract, and is involved in migraine pathophysiology. It is possible that CGRP expression patterns evolve over the course of childhood development. For example, in a guinea pig animal model, mesenteric peptidergic nerve plexus density was highest at birth and decreased to half the density by age 2 years. It is also possible that the developmental changes are all occurring in the brain, and how the brain processes, perceives, and localizes signals within the body.

While there has been little research in treating abdominal migraine, a small study demonstrated that pizotifen was superior to placebo for migraine prevention. In the United States, cyproheptadine would probably be the most analogous medication. In our pediatric headache program at the University of California San Francisco, we have successfully treated children with “status abdominal migrainosus” with intravenous dihydroergotamine. However, if we view abdominal migraine as migraine—just a phenotypic variant along the age spectrum—then it follows that anything used to treat migraine could also reasonably be used to treat abdominal migraine.

Cyclical vomiting syndrome (CVS)

Cyclical vomiting syndrome is characterized by repeated episodes of intense nausea and vomiting, often with abdominal pain. Patients tend to wake up out of sleep at a particular time of night with symptoms. For example, a typical history would be, “Every 8 weeks she wakes up between 2:00 and 4:00 am with vomiting, and it lasts for 24 h.” The vomiting can be severe. Patients may need to go to the emergency department for rehydration. CVS is most common in school-age children, but teens and adults can be affected.

It is important to ensure that the child is normal in between episodes, and not experiencing developmental regression or delay or seizures. Recurrent vomiting episodes with any of these other red flags would suggest a possible inborn error of metabolism or one of the developmental occipital lobe epilepsies such as Gastaut-type epilepsy or Panayiotopoulos syndrome. Gastrointestinal pathology is also on the differential.

In an adolescent patient presenting with symptoms concerning for CVS, it is essential to ask about cannabis use. This can be done as part of a HEADSS assessment with the adolescent alone. Cannabinoid hyperemesis syndrome (CHS) can mimic CVS and cause episodes of intense nausea/vomiting. It most commonly occurs in those who use cannabis daily or near daily, and who have been doing so for months to years, but can occur even with less frequent or shorter duration use. Patients may engage in hot water bathing behavior during episodes, though this is not specific to CHS and can be seen in those with CVS as well. Prolonged use of cannabinoids can lead to downregulation of central cannabinoid receptors (CB1 receptor). Under normal circumstances, endogenous endocannabinoids would be released and bind the CB1 receptors to help prevent nausea when the body is under stress. Downregulation of these receptors inhibits this system. Unfortunately, cannabis is stored in fat tissues, so even once intake has ceased, it can still take weeks to months for stores to empty and receptor patterns to return to normal levels. Thus, symptoms do not necessarily improve with just a few weeks of abstaining from cannabis, which can lead adolescents to conclude that their cannabis use was not the problem. To determine definitively whether cannabis use is contributing to symptoms, several months’ abstention may be needed. It is possible that individuals with CVS have a naturally down-regulated CB1 receptor system, and certain genotypes of this receptor are associated with CVS risk. Cannabis use may mimic “primary CVS” by provoking the same phenotype.

Treatment of cyclic vomiting syndrome can be challenging. For one thing, vomiting can be so profuse and rapid in onset that oral routes of administration are often simply untenable. Nasal sprays, intramuscular or subcutaneous injections, and rectal suppository routes may be preferable (though teens generally do not favor the latter). If there is a gap between onset of symptoms and vomiting, oral administration of a rapidly dissolving antiemetic may facilitate administration of oral NSAIDs or triptans. If the patient needs IV fluid rehydration, acute medications can also be given intravenously. For prevention, a trial in children found comparable effectiveness of amitriptyline and cyproheptadine. A second trial comparing amitriptyline to topiramate favored amitriptyline. The neurokinin-1 receptor antagonist, aprepitant, may help both acutely or as a preventive taken twice weekly.

Conclusions

Migraine is a disorder of amplified or distorted sensory perception. The disorders currently referred to in ICHD-3 as “episodic syndromes that may be associated with migraine ,” namely: benign paroxysmal torticollis, benign paroxysmal vertigo, abdominal migraine, cyclic vomiting syndrome, and infant colic (appendix section), can best be thought of as developmentally phenotypically distinct manifestations of migraine. Formal studies are needed to guide treatment of each sub form. In the meantime, a useful starting point would be to think of them as migraine and to manage them as such.