Migraine in Children Under 7 Years of Age: a Review

DOI: https://doi.org/10.1007/s11916- 020- 00912- 5

Abstract-Summary Within primary headaches in this age, migraine especially, turns out to be a disorder affecting up to 4% of the general population.

Migraine in children under 7 years of age represents an important challenge for

clinicians.

The objective of this manuscript is to provide a comprehensive review of epide-

miologic, clinic, and therapeutic aspects of migraine in this age.

Current literature data show that migraine has some differences, especially in

clinical and therapeutic terms, in this age group compared to subsequent ages.

Open questions related to the several undefined features of migraine in this age

are reported.

Migraine in this pediatric population is absolutely not rare, represents an impor-

tan clinical challenge and probably has a negative predictive role.

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3 Diagnosis

Introduction In this age as well as in general population, some recent studies [117, 118] show an increased disability from primary headaches, and especially migraine.

The rarity of studies on headaches in prescholar age probably depends on the difficulty that children experience to describe painful sensations, along with the “mythological” idea that primary headaches were typically well identified in scholar age children or adolescents only.

It is really surprising that recent Pubmed search results show just over a dozen studies on headaches in preschoolers compared to the thousands of papers pub- lished in the last 30 years on headache in school age children and adolescents [119]. Since studies on the maturation of the nervous system demonstrate that all ana- tomical and functional structures responsible for the expression and features of pain are already developed in infancy, is clear that a child under 7 years of age can suffer from almost all types of primary headache.

Epidemiology of Migraine in Children Under 7 Years of Age Arruda and others [120] in a study in a Brazilian pediatric population estimated in the groups under 6 years and up to 7 years, an overall prevalence of migraine with or without aura of 5.46%, chronic migraine of 1.79%, probable migraine up to 29.33%, infrequent tension episodic headache up to 3.01%, frequent tension epi- sodic headache up to 2.37%, and probable tension headache up to 12.61% (also in this study, there are no distribution according age 0–7, but only < 6 and < 7 years old). There are no other epidemiological studies that explore the prevalence of the dif- ferent headache types in preschoolers and in all the studies conducted in evolutive age, the distribution of migraine in the 0–7-year range is not reported.

Reported Headache Distribution in Preschoolers’ Clinical Series Until a few years ago, a unique study on chronic and/or recurrent headache in a large sample was available [121].

This study [121] had some methodological peculiarities because conducted on a sample of subjects observed by a neurologist before the completion of 10 years and whose headaches began before 7 years.

The study by Chu and Shinnar [121] indeed showed some distortions in the prev- alence and distribution of chronic and most frequently recurring headaches; more- over, they adopted diagnostic criteria pre-IHS classification, making more difficult the comparison with subsequent studies.

In the last 15 years have been published [122–127] several studies reporting the

different distribution of headaches subgroups.

In a study, we confirmed that even at this age, secondary headaches are frequent

(about 26%) and could be dangerous [123].

Neuroanatomical and Functional Development of Nervous System Pathways and Neurotransmitters Involved in Migraine Since in studies on embryo-fetal development is universally preferred the term GA, in this review, we have adopted GA and WG to define the developmental age of the embryo-fetal pathways involved in migraine.

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Neurofunctional pathways involved in migraine can be recognized from 8 weeks of gestation (WG) with trigeminal free sensory nerve endings reaching the oral mucosa and then the facial epithelium.

Neurochemical maturation involved in pain perception is characterized by appearance in dorsal horns of substance P (SP), acetylcholinesterase and enkephalin at 5–7 WG, prostaglandins, somatostatin and neuronal nitric oxide synthase from the 8 WG.

Neuropeptide Y, involved in the descending pain modulation pathway, is identifi- able in spinal cord at 12 WG, and at 14 WG spinal cord cell differentiation in the dorsal horn is associated with the synthesis of GABA and glutamate, both character- ized at this stage of development by an excitatory effect [128, 129].

Risk Profiles for Potential Subsequent Early Development of Migraine Using functional MRI (fMRI), it has been demonstrated that in newborn infants, pain-related brain activity is similar to that observed in adults [130] and that infants with a more functionally connected DPMS, show a greater ability to regulate their pain experience and dampen the magnitude of their brain activity in response to incoming nociceptive input [131].

A possible effect of early alteration of pain circuitry plasticity, consisting in mal- functioning of descending inhibitory nociceptive pathways, increased activity of facilitatory nociceptive pathways, and altered neuronal synapses, could be a central hyperexcitability, corresponding to central sensitization, which is suspected to be involved in chronic headache [132].

Although neonatal care protocols aim to prevent the at-risk newborns from being negatively affected by the consequence of detrimental response strategies to early life pain experiences, prenatal and perinatal insult during neuronal development are still having long-term impacts on the nervous system circuitry through neuronal plasticity.

An asymmetry in brain autonomic control has also been demonstrated in adults in response to pain, with a predominant parasympathetic activation in left-side migraineurs and a predominantly right-side migraineurs [133].

sympathetic

function

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Clinical Features of Migraine These difficulties appear to be even more evident in preschool age as evidenced by an important recent Italian study [126] which underlines how with the current crite- ria about 30% of children under 6 remain unclassifiable and 30% is classified as probable migraine.

A criteria modification, specifically excluding the migraine attack duration and introducing the positive familiarity, increased migraine diagnosis and reduced the unclassifiable headaches to 8.5% of children under 6 years.

The few existing studies in preschoolers often report incomplete and non- homogeneous information on clinical features of migraine and the variable prevalence of symptoms could be related to the different median age consid- ered [119].

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More prospective studies on larger population are necessary, aiming to obtain more careful description of the migraine attacks and to better understand similari- ties and differences between age groups.

Therapy of Migraine in Preschoolers Symptomatic or prophylactic pharmacological trials of migraine in younger chil- dren have not been published yet.

A study showed good and well-tolerated responses to assumption of triptans in a small population of migraineurs children (ten children), including children below 7  years age [134], without specifying the age ranges considered and the relative response rates to the treatment.

No randomized trials are available on the treatment of children under the age of 7, but pizotifen, cyproheptadine, propranolol, and amitriptyline were suggested for prophylactic treatment [119].

In this subgroup of migraineurs, non-pharmacologic treatments as regular meals, rest, good sleep, avoidance of factors triggering or aggravating the attacks, are usu- ally suggested.

A study comparing migraineurs under 6 years to children aged more than 6, and aiming to evaluate the efficacy of non-pharmacologic strategies (avoidance of dietary triggers, excessive exposure to sun, and good sleep hygiene), evaluating attack frequency reduction from 50 to 75% [135].

Follow-up of Preschoolers with Migraine Hernandez and others [136] studied a pediatric migraine population (284 children), including 69 children below 6 years, of whom 181 children (50 under 6 years) were followed for a period ranging from 2 to 10 years.

The first prospective study on pediatric population under 7 years monitored 25 children for a mean duration of 4.2 years (range 2.8–6.6 years), but only five chil- dren were classified migraineurs with the 2004 2nd IHS criteria and only 1 had also persistent headache at follow-up [137].

An original study [138] compared a population of children with migraine and

tension-type headache in at 6 and 13 years of age.

We [139] recently showed in the first long-term follow-up study (mean 17 years, range 15–23 years) that 75% of migraineurs below 6 years of age had a migraine persistence.

Open Questions If up to 2005 only very few studies [122, 140] specifically pointed on migraine under 7 years, the next clinical epidemiological and follow-up studies on preschool migraineurs demonstrate clearly that migraine in this pediatric population is abso- lutely not rare.

Migraine in preschoolers can represent an important clinical challenge and prob-

ably has a negative predictive role for its persistence in later ages.

More studies are based on retrospectively collected data, mainly from parents’ interview, almost all are on selected clinical population, frequently with incomplete descriptions of the clinical features, the follow-up studies present important

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drop- out and are based on small groups, and the management of migraine is gener- ally poorly described.

Their specific role on clinical, prognostic, and therapeutic dimensions of

migraine, across the different ages, are not been well defined.

Clinical evidence suggests that migraine in this age may present several differ-

ences in comparison to school age children and adolescents.

Acknowledgement A machine generated summary based on the work of Raieli, Vincenzo; D’Amico, Antonina; Piro, Ettore. 2020 in Current Pain and Headache Reports.

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