Ophthalmologic Manifestations of Pediatric Headache
- Author: Marc E Lenaerts, MD, FAHS; Chief Editor: Hampton Roy Sr, MD more...
Background
Children frequently experience headaches, which can be age specific or the beginning of a lifelong syndrome. The approach of headache in this age group is peculiar in several ways, as follows: (1) in a discipline where diagnosis is based on history, an underestimation is inevitable; (2) the verbal expression of pain itself is language-dependent and other behavioral indicators have to be relied upon; (3) frequently symptoms other than pain may be at the forefront of the clinical picture; (4) except in young children, the frequency of secondary headaches is lower than in adults; and (5) in young patients, pharmacotherapeutic interventions are limited but nonpharmacologic interventions can be more efficient.
Because of a high placebo success rate, researchers and companies are not eager to design and set up pharmacologic trials for pediatric headaches, including in the emergency setting.[1, 2]
No headache classification exists that is specific for children, and such patients are underrepresented in the headache literature.
Migraine is the most frequent chronic headache in children; therefore, it will receive most of the attention in this article.
Pathophysiology
Although much remains to be discovered, the pain in migraine attacks supposedly is due to activation of the trigeminovascular system (see image below). Synaptic boutons of the perivascular branches of the trigeminal nerve at the level of meningeal and basal cerebral vessels release the following proinflammatory mediators when the nerve is stimulated: substance P, calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP). The initial triggers are still poorly understood. The mediators create neurogenic inflammation, including local rupture of the blood-brain barrier, and trigger vasodilatation, further stimulating the trigeminal nerve terminals.
Trigeminovascular system.The trigeminal nerve fibers around basal cerebral and meningeal vessels are triggered (various stimuli are possible), and a vicious circle starts where the nerve terminals release calcitonin gene-related peptide (CGRP), substance P, vasoinhibitory peptide (VIP), and other mediators of local neurogenic inflammation and vasodilatation. The latter further stimulates the nerve endings. On the other end of the nerve, painful messages are transmitted toward central centers, including thalamus and cortex, and the sensation of pain arises.Modern drugs, such as the triptans, act at 3 levels, via 5-HT 1 B and D receptors; they vasoconstrict the vessels, they reduce the release of the above-mentioned mediators, and they decrease the central transmission of pain impulses. On the other end, pain afferent messages are transmitted centrally. Whether this system is abnormal in migraineurs versus healthy people, and whether it is genetically determined, is not known. Evidence exists of cortical hyperexcitability in migraineurs, which may be linked to a defect in the central catecholaminergic systems. Low magnesium levels also may play a role.
In 1993, a gene mutation was found on chromosome 19, locus p13, in a pedigree experiencing familial hemiplegic migraine (FHM). Later, hemiplegic migraine in other families was mapped to chromosomes 1 and 2. At this time, 3 genes have been discovered, leading to 3 categories of FHM: FHM I (locus 19, q 13) codes for the calcium channel CACNA1A gene; FHM II (locus 1, q 21) codes for the Na-K ATPase ATP1A2 gene[3] ; and FHM III (locus 2, q 24) codes for the sodium channel SCN1A gene.[4] Defects in ion channels resulting in excessive glutamate activity explain the effect of the mutations, which play a role in the aura. Cases of migraine due to a single mutation remain the exception.[5, 6]
White-matter T2 MRI hyperintensities are observed in higher frequency in migraineurs, especially in the posterior circulation territories. The pathophysiological implication remains unclear.
Chronic transformation of migraine is believed to be due to spatial and temporal, central and peripheral sensitization, which correlates clinically with cutaneous allodynia.
Tension-type headache pathophysiology is still poorly understood; a combination of muscular factors, abnormal pain perception mechanisms, and central emotional abnormalities exist, all possibly linked to brainstem serotonergic interneurons. Furthermore, central and peripheral sensitization is involved. Contrary to the usual belief, the relevance of muscle contraction itself is marginal, especially in the chronic form.
Epidemiology
Frequency
United States
Throughout the medical literature, estimates of overall frequency of headache in children vary among authors. Starfield screened 2500 children and found that 11% experienced chronic morbidity; among those children, about 20% had headache, roughly one half of which had migraine.
There is a steep increase in the cumulative prevalence of headache in children and adolescents. According to Split et al in a large survey, 4% of children have migraine by the ages of 7 through 15; by age 15 28% have migraine and 75% have headaches in general.[7] Lewis et al, in a meta-analysis of over 25,000 persons, found the incidence of migraine to be 2% by ages 3-7; 7% by ages 7-11; and 20% by ages 11-15.[8] In another meta-analysis, headache in general was approximately 60% by age 7.
International
In a widely cited study, Bille analyzed a questionnaire of 8993 children aged 7-15 years in the city of Uppsala in Sweden and found that 59% had a headache in their life.[9, 10] Also, in a systematic questionnaire of 2941 children, the prevalence of headache was 37% at age 7 years, increasing to 69% by 14 years; migraine accounted for 2.7% and 10.6%, respectively.
According to Sillanpaa, at puberty (age 13 y) migraine prevalence is around 11% but increases over time.[11, 12] Secondary headaches are the ones that are most frequently encountered before the age of 5 years. Migraine headache can occur as early as a few months of age. A higher prevalence of migraine seems to exist in city dwellers. Chronic tension-type headache occurs in 0.9% of 15 year-olds. Long-term prognostic studies are scarce, but Brna et al reported over a 20-year follow-up that 73% of patients still had headaches.[13] In a follow-up study of 200 patients from a headache clinic over 6 years, 48% of initial migraineurs remained migraine sufferers; 26% became tension-type headache sufferers; and 26% became headache free. Similar numbers were observed for initial tension-type headache sufferers but with a slightly higher headache-free rate (41% remained with tension-type headache; 21% developed migraine; and 38% became headache-free).
Mortality/Morbidity
- No mortality is associated with primary headaches, and that of secondary headaches depends purely on the underlying cause.
- Morbidity includes psychological impairment and decreased quality of life, especially for persons who experience chronic migraine. It was recently emphasized again how children who suffer from migraine are more impaired than children who do not suffer from headaches or even children who suffer from tension-type headache, in terms of medication use, school-nurse visits, and school absences. Three million bedridden days per month in the US are attributed to headache, and more than 50% of absentees from headache average at least 2 days of absence per month. For almost 1 million children who have migraine, over 150,000 school days are missed.
- Migraine in general, but especially migraine with aura (any type [typical aura, hemiplegic migraine, basilar migraine]), seems to be associated with a slightly increased risk of stroke, but overall, the risk remains very low. Other conditions comorbid with migraine have been observed, including irritable bowel syndrome, sleep disorders, bruxism, systemic lupus erythematosus, and obesity.[14]
- Frequent headaches, as with other chronic pain syndromes, can be psychologically distressing and can have major implications on the life of the growing individual. According to Battistutta et al, chronic tension-type headache is comorbid with psychiatric illnesses such as depression and anxiety disorders, internalization syndrome, and attention deficit and anger-control deficit in adolescents. However the relationship between the psychological condition and the headache syndrome is far from simple and has not yet been resolved. The clinical implication is to attend to the entire symptomatology of the child.[15]
- Recent reports indicate a higher incidence of ataxia, whether clinical or subclinical during provocation tests. These could correlate with white matter lesions on MRI, especially in the cerebellum.
Race
No specific report exists regarding differential incidence by race in children, but migraine frequency in adults in the US declines from whites to African-Americans to Asians.
Sex
Before puberty, males are affected slightly more by migraine than females; thereafter the relationship is inversed, with 3 times more female than male migraineurs in adulthood. Other headache types are distributed more evenly.
Age
In a systematic survey of close to 3000 children, Sillanpaa showed the increase in frequency with age, from 37% at age 7 years to 69% by age 14 years.
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