Migraine is a common disorder in children. Estimates indicate that 3.5–5% of all children will experience recurrent headaches consistent with migraine. Management consists of identifying triggering factors, providing pain relief, and considering prophylaxis.
No specific diagnostic test is available; the diagnosis is made by history and examination. The International Classification of Headache Disorders, 3rd edition, beta version [ICHD-3 (beta)] was published in 2013 and serves as a reference for signs and symptoms currently used as diagnostic criteria. The history should address the following:
Manifestations of migraine may vary according to patient age, as follows:
A thorough general physical examination and a detailed neurologic examination are indicated. All examination findings should be completely normal. Follow-up evaluations are necessary for patients with any of the following:
Laboratory and imaging studies are unnecessary for the diagnosis of migraine but may be indicated for the exclusion of other disorders. Investigative studies that may be considered include the following:
Management of pediatric migraine has the following 3 facets:
Treatment of mild, infrequent attacks consists primarily of rest, trigger avoidance, and stress reduction.
Education regarding migraine triggers includes the following:
Measures that may be helpful for managing acute attacks include the following:
Analgesic and abortive therapies are for occasional acute attacks and should not be used frequently (frequent use may result in medication-overuse or "rebound" headaches).
Possible medications for migraine prophylaxis include the following:
In cases of status migrainosus, aggressive therapy is warranted, including the following 5 components:
Migraine is a common disorder in children. Estimates indicate that 3.5-5% of all children will experience recurrent headaches consistent with migraine. As in adults, most children (approximately 60%) have migraine without aura. Approximately 18% have only migraine with aura, 13% have both, and 5% experience only aura.
Migraines are incapacitating, throbbing headaches frequently located in the temples or frontal head regions. In children, the headaches are often bilateral (frontotemple) and may be nonthrobbing. Aura is infrequent prior to age 8 years. During the migraine episode, the child often looks ill and pale. Nausea and vomiting are frequent, particularly in young children. Patients avoid light (photophobia), noise (phonophobia), strong odors, and movement. Relief typically follows sleep.
Initial evaluation focuses on excluding other conditions. Management consists of identifying triggering factors, providing pain relief, and considering prophylaxis.
Conditions that are relatively common in the pediatric population and are thought to be variations and/or precursors of migraine include the following:
A migraine attack has 4 potential phases, as follows:
Migraine with aura (previously known as classic migraine) and migraine without aura (previously known as common migraine) each have a premonitory phase, or prodrome, which may precede the headache phase by up to 24 hours. During this phase, the following features may occur:
These premonitions are often more pronounced in migraine without aura than in migraine with aura. Children with frequent migraine headaches or migraine variants often have a vague feeling that something is different in their world. They often learn to recognize these premonitions but find them difficult to explain to their parents or physicians.
An aura is a focal cerebral dysfunction that immediately precedes or coincides with headache onset. The aura may occur without headache or may be more disturbing than the headache. Only 10-20% of children with migraine experience an aura. The aura usually precedes the headache by less than 30 minutes and lasts for 5-60 minutes. Motor auras tend to last longer than other forms of aura.
Children are often unaware of their aura or are unable to describe it. Pictorial cards that illustrate typical visual auras may aid in obtaining an accurate history.
Visual auras (which are often reported as moving or changing shapes) are the most common form in children. They may consist of any of the following:
Nonvisual auras include the following:
Aura symptoms vary widely within and between attacks. Patients who eventually develop migraine with aura present at a younger age than do patients who experience migraine without aura.
The actual headache phase of the migraine attack is usually shorter in the pediatric population than in adults; pediatric headaches can last 2 to 72 hours (whereas diagnostic criteria for migraine in adults includes duration of 4 to 72 hours). Some young patients report headaches lasting 10-20 minutes. Childhood migraine headaches are often less severe than adult migraine headaches.
During the headache phase, the migraineur may experience any of a range of associated symptoms, as follows:
After the headache phase, the patient may feel either elated and energized or, more typically, exhausted and lethargic. This stage of migraine may last from hours to days.
A patient may experience varying types of headaches, including different forms of migraine. The 2 most frequent forms are migraine without aura (previously known as common migraine) and migraine with aura (previously known as classic migraine and encompassing headaches referred to as complicated, ophthalmic, or hemiplegic migraines). Migraine equivalents or migraine variants also occur and are differentiated by patient history.
Migraine with aura is characterized by visual, sensory or other neurologic symptoms, followed by a severe, throbbing headache. It lasts between 2 and 72 hours. Headaches usually occur 1-2 times per month, but the frequency may vary considerably among individuals.
Of children with migraine, approximately one third have migraine with aura. Approximately 5% of affected children have aura without headache.
The visual disturbance may consist of seeing sparkling lights or colored lines, visual hallucinations, blindness, hemianopia, blurred vision, or micropsia. The aura usually precedes the headache by less than 30 minutes and lasts 5-60 minutes. Other, less common auras consist of sensory symptoms or focal motor deficits (hemiplegia).
Common migraines, which lack an aura, occur in 60-85% of migrainous children. In young children, the headache is more often bilateral, orbital, or frontotemporal, and the pain may radiate to the face, occiput, or neck. The pain is throbbing and/or pulsating in quality and of moderate to severe intensity. It is aggravated by physical activity and relieved by sleep. Common accompanying symptoms in children are severe gastrointestinal (GI) symptoms, irritability, and pallor with dark circles under the eyes.
Migraines without aura are associated with nausea, vomiting, or both and are frequently accompanied by sensitivity to light, sound, and movement. If untreated, these headaches can last up to 72 hours. In children, duration of head pain is often less than 4 hours, which is shorter than is typical for adult migraine.
Migraine with brainstem aura (also known as basilar migraine, basilar artery migraine, or Bickerstaff syndrome) is a subtype of migraine with aura. It most commonly is observed in adolescent and young adult females. Headache pain is located in the occipital area.
Basilar migraine is characterized by disturbances in function originating from the brainstem, occipital cortex, and cerebellum. (The neurologic symptoms are usually brief.) The occipital headache must have at least 2 of the following aura symptoms, which are associated with dysfunction originating from the occipital and/or brainstem area:
A history of typical migraine exists in 86% of families studied. Many patients experience migraine with brainstem aura intermingled with typical migraine attacks.
Familial hemiplegic migraine (FHM) is an autosomal dominant form of migraine with aura; at least one first-degree or second-degree relative has migraine with aura involving weakness. Episodes are marked by a prolonged hemiplegia accompanied by numbness, aphasia, and confusion. The hemiplegia may precede, accompany, or follow the headache, and symptoms may last for hours or for even as long as a week. The headache is usually contralateral to the hemiparesis. Some FHM attacks are associated with cerebellar ataxia.
Other more severe symptoms of FHM may include coma, fever, and meningismus; progressive ataxia, nystagmus, gait unsteadiness, limb incoordination, and dysarthria.
Genetic abnormalities have been identified; CACNA1A gene mutations (coding for calcium channel) on chromosome 19 in FHM1; mutations in the ATP1A2 gene (coding for a K/Na-ATPase) on chromosome 1 in FHM2; and mutations in the SCN1A gene (coding for a sodium channel) on chromosome 2 in FHM3.[1]
Consider structural lesions, vasculitis, cerebral hemorrhage, brain tumor, mitochondrial myopathy, encephalopathy, and lactic acidosis in the differential diagnosis. If hemiparesis is always on the same side, consider a vascular abnormality.
Acute confusional migraine is not classified under the ICHD-3 (beta). This type of migraine is uncommon and usually occurs early in the second decade of life. Acute confusional migraines are characterized by transient episodes of amnesia, acute confusion, agitation, lethargy, and dysphasia precipitated by minor head trauma. Affected children are delirious, restless, and combative and appear to be in pain, but they do not complain of headache.
The child may have a receptive or expressive aphasia, and the confusional state may either precede or follow the headache. Some children also experience recurrent episodes of transient amnesia and confusion.
Episodes typically last less than 6 hours and are followed by deep sleep. Upon awakening, the child is normal and is amnestic for the attack.
The child may not have a history of headache, but he or she usually develops typical migraine attacks in the future. Exclude drug abuse; brain magnetic resonance imaging (MRI) results should be normal.
These include status migrainosus, which is a severe form of migraine in which the headache phase is continuous for more than 72 hours.[2, 3] The headache is protracted, disabling, and unresponsive to vigorous outpatient treatment. Patients usually have a preexisting migraine history.
Persistent aura without infarction involves aura symptoms which last one week or more, without stroke demonstrated on neuroimaging.
Migrainous infarction and migraine aura-triggered seizure are also classified as complications of migraine.
This rare form of migraine is characterized by a severe, unilateral headache with prolonged oculomotor palsies involving the third, fourth, or sixth cranial nerves. Ophthalmoplegia may precede, accompany, or follow the headache; recurrent episodes may cause permanent oculomotor deficit.
These migraines involve repeated attacks of monocular scotoma or blindness, usually followed by headache. The patient must have normal ophthalmologic examination findings between attacks. Retinal abnormalities and/or embolism should be excluded.
The below-described migraine equivalents are underrecognized and underreported manifestations of childhood migraine. They are often forerunners of the typical migraine. Occasionally, variant migraines alternate with typical migraine symptoms.
This rare disorder is characterized by repeated episodes of head tilting and is associated with nausea, vomiting, and headache. Attacks usually occur in infants and may last from hours to days. Consider posterior fossa abnormalities in the differential diagnosis.
This condition is characterized by brief episodes of vertigo, disequilibrium, and nausea. It is usually found in children aged 2-6 years. The patient may have nystagmus within, but not between, the attacks. The child does not have hearing loss, tinnitus, or loss of consciousness. Symptoms usually last only a few minutes. These children often develop a more common form of migraine as they mature.
Brain MRI can be performed to exclude posterior fossa abnormalities, especially if abnormalities in the neurologic examination are found between episodes.
This syndrome is characterized by a migraine aura without headache, usually visual auras, and a female predominance. A positive family history of migraine is essential. Ophthalmic migraine is a variant of acephalic migraine.
Abdominal migraine is characterized by recurrent bouts of generalized abdominal pain with nausea and vomiting; no headache is present. After several hours, the child can sleep and later awakens feeling better.
Abdominal migraine may alternate with typical migraine and usually leads to typical migraine as the child matures.
This syndrome is characterized by recurrent periods of intense vomiting, at least 4 times per hour, separated by symptom-free intervals, with attacks occurring at least 1 week apart. Many patients with cyclic vomiting have regular or cyclic patterns of illness. Symptoms usually have a rapid onset at night or in the early morning and last at least 1 hour and up to 10 days (usually 6-48 hours). Associated symptoms include the following:
Headache often does not appear until the child is older. Migraine-associated cyclic vomiting syndrome usually begins when the patient is a toddler and resolves in adolescence or early adulthood; it rarely begins in adulthood. More females than males are affected by cyclic vomiting.
Infections, psychological stress, physical stress, and dietary triggers are often clearly identified in the patient's history. Examples of triggers include cheese, chocolate, monosodium glutamate (MSG), emotional stress, excitement, or infections. Usually, the parents or siblings have a family history of migraine.
Cyclic vomiting syndrome is a diagnosis of exclusion. It is important to differentiate cyclic vomiting related to migraine from nonmigraine cyclic vomiting conditions. Other causes of cyclic vomiting include the following:
Children with cyclic vomiting associated with migraine tend to experience fewer severe vomiting episodes per hour and fewer attacks per month than those with cyclic vomiting associated with other GI disorders. These children exhibit a higher incidence of pallor, abdominal pain, headache, social withdrawal, motion sickness, photophobia, and physical exhaustion.
Cyclic vomiting associated with developmental delay, poor growth, seizures, and maternal migraine may be associated with mutations of mitochondrial DNA. When such mutations are suggested, serum lactate/pyruvate and urine organic acid levels should be obtained, preferably during an attack.
The exact cause of migraine is unknown. Migraine is most likely a heterogeneous disorder and has trigger factors and multiple physiologic causes. Although many of these diseases do not develop until middle age, early recognition of migraine risk factors may help the child to adopt a healthy lifestyle.
The cause of pain in persons with migraine is poorly understood. Migraine pain does involve cranial blood vessels, trigeminal innervation of these vessels, and reflex connections of the trigeminal system with cranial parasympathetic outflow. Most patients experience pain in the distribution of the ophthalmic division of the fifth cranial nerve and/or in the distribution of C2.
Migraine pain may in part be related to the ventral propagation of cortical spreading depression to meningeal trigeminal nerve fibers. This appears to cause the release of a number of vasoactive substances, including neurokinin A, substance P, and calcitonin.
Vascular theory
The vascular theory, as proposed by Graham and Wolff in 1938, was long accepted as a plausible explanation of the characteristic sensory and motor disturbances in migraine with aura. The vascular theory views migraine as having 2 phases.
The first phase (the prodromal phase) is characterized by vasospasm, which causes focal cerebral ischemia and transient neurologic symptoms. The second phase results from compensatory vasodilation of the intracranial and extracranial vasculature. Brain acidosis and stretching of pain fibers in arterial walls would then cause a pulsating headache.
Although the vascular theory influenced medical literature for many decades, the involvement of the cranial vessels in the initiation and pathogenesis of migraine is now under considerable debate.
Neuronal theory
The vascular theory was replaced by the neuronal theory, which suggests that migraine with aura is related to the paroxysmal depolarization of cortical neurons. However, neither theory adequately explained the pathophysiology of migraine.
Trigemino-vascular theory
At present, the most widely accepted model of migraine is the trigemino-vascular theory. This theory proposes that migraine results from depolarization of cortical neurons followed by a reduction in posterior cerebral blood flow.
According to the trigemino-vascular theory, migraineurs have a hyperexcitable cerebral cortex. Genetic factors cause disturbances in neuronal ion channels, which allow a variety of external and/or internal factors to trigger episodes of regional neuronal excitation followed by cortical depression.
The initial phase is a wave of spreading cortical depression, which is associated with suppression of spontaneous electroencephalographic (EEG) activity and regional oligemia. The cortical depression begins in the occipital region, moves anteriorly during the course of an attack, and is thought to be responsible for the patient's aura, focal neurologic symptoms, or both.
This wave of cortical depression is preceded by brief ionic changes in neurons and glia causing prolonged depolarization and depression of EEG activity. These ionic changes move across the cortical gyri at 2-3mm/min, resulting in decreased neuronal activity.
The cortical depression stops at the central sulcus and then spreads ventrally to the meningeal trigeminal fibers, causing headache. Brain ion homeostasis falters, allowing an efflux of excitatory amino acids from nerve cells and enhanced energy metabolism. Activation of N -methyl-D-aspartate receptors may be involved. Decreased blood flow to the occipital cortex follows in response to the decreased neuronal activity.
A reactive hyperemic phase follows. This increased blood flow does not precisely follow the timing of the head pain.
Serotonin (5-hydroxytryptamine, or 5-HT) also seems to play a role in the pathogenesis of migraine. Intermittent neuronal discharges from serotonergic neurons in the pons may cause an initial discharge in the ipsilateral occipital cortex. This discharge could then cause a wave of spreading excitation followed by depression of neuronal activity.
During a migraine attack, urine levels of the serotonin metabolite hydroxyindoleacetic acid increase significantly. Serotonin is released from platelets at the beginning of an attack. After onset and for the duration of the headache, intraplatelet serotonin levels decrease. Serotonin turnover is also reduced during a migraine attack. Between attacks, however, migraineurs have increased synthesis of serotonin.
In addition, several serotonin receptors appear to be important in the pathophysiology of migraine. The 3 most important receptors are 5-HT1, 5-HT2, and 5-HT3. The 5-HT1 receptors are inhibitory, and the 5-HT2 receptors are excitatory. All triptans are 5-HT1 agonists, while many prophylactic agents (eg, beta blockers) are 5-HT2 antagonists. An injection of serotonin during an attack decreases migraine symptoms but is associated with many unpleasant adverse effects.
Investigators have also proposed that a sterile inflammatory process causes the release of vasoactive neuropeptides, such as substance P and neurokinin A, from the trigeminal nerve. This causes vasodilatation of the arterioles and arteries, which activates endothelial cells, mast cells, and platelets.
In turn, these release vasoactive substances such as histamine, serotonin, peptikinins, prostaglandins, catecholamines, and slow-reacting substances of anaphylaxis. These substances cause contraction and relaxation of smooth muscle and the symptoms of migraine. The sterile inflammation process is proposed to increase the pain and lengthen the duration of a migraine attack.
It is also known that obesity causes the release of tumor necrosis factor-alpha and other cytokines from adipocytes, which results in a low-grade systemic inflammatory state. Obesity may therefore play a role in headache predisposition.[4]
Nitric oxide (NO) has been found to cause cerebral arterial dilation and delayed headache in migraineurs; however, it has not been found to cause aura.
NO regulates blood pressure, inhibits platelet function, and acts as a neurotransmitter. It is involved in the central processing of pain and in the regulation of vasodilatation in the central nervous system and is produced by NO synthase in neurons. NO donator agents (eg, nitroglycerin, glyceryl trinitrate, isosorbide) cause migrainelike pain after 3-10 hours. Monomethyl-L-arginine, a specific inhibitor of NO synthase, is an effective treatment for migraine pain.
Ion channels control and maintain electrical potentials across cell membranes. Mutations in ion channel genes cause numerous neurologic disorders. Brain-specific P/Q-type voltage-gated calcium channel alpha-1A subunit gene mutations are responsible for such diverse phenotypic symptoms as typical migraine with or without aura, familial hemiplegic migraine (FHM), episodic ataxia type 2, and spinocerebellar ataxia type 6.
Half of the known FHM cases studied have linkage to chromosome 19p13. Different missense mutations (R192Q, T666M, V714A, I1811L, G4644T) cause FHM with different phenotypic manifestations. Linkage to a separate gene on chromosome 1 has also been reported. An estimated 5% of migraineurs may carry a mutation in a calcium channel gene.
Many migraine families demonstrate a predominant maternal inheritance pattern that may be caused by mitochondrial dysfunction. Migraine with aura and migraine without aura are each associated with abnormalities in brain energy metabolism; thus, mitochondrial dysfunction may be involved in a subset of patients.
In 1998, Schoenen et al found that a high dose of riboflavin (400mg/day) was an effective migraine prophylaxis, reducing attack frequency by 56%. The full benefit is obtained after 3 months. Riboflavin was postulated to improve the altered mitochondrial energy metabolism.[5]
As previously stated, early recognition of migraine risk factors may help a child to adopt a healthy lifestyle.
The familial occurrence of migraine has been recognized for many years. The significantly higher concordance rate among monozygotic twins compared with dizygotic twins supports a strong genetic basis for this condition. Studies also suggest that migraine with aura is genetically distinct from migraine without aura; however, neither migraine type appears to have a distinctive pattern of Mendelian inheritance.
Hormonal changes and fluctuations also appear to play a role. Prior to puberty, migraine occurs equally among boys and girls. With the onset of puberty, migraine becomes significantly more prevalent among females (approximately 3 times as common).
An estimated 20–50% of migraineurs are sensitive to certain foods. These dietary triggers may provoke a migraine attack. Helping the child learn to recognize and avoid these triggers is helpful but often difficult. A headache diary can be useful for identifying triggers; a pattern often emerges after 6–8 weeks. Note that some patients inappropriately use the diary to create elaborate, restrictive diets that could harm normal growth and development.
Substances that may precipitate migraine include prostaglandin E and the vasoactive amines tyramine and phenylethylamine. Foods such as chocolate, cheese, and red wine are known to contain these compounds and often initiate migraine in adults. Diet and foods containing vasoactive amines appear to be much less important in children.
Tyramine
Patients with low levels of phenolsulfotransferase P are believed to be sensitive to dietary monoamines such as tyramine and phenylethylamine. Cultured dairy products (eg, aged cheese, sour cream, buttermilk), chocolate, and citrus fruits are believed to cause vasodilation in predisposed individuals.
Beverages
Alcoholic beverages, especially red wine, and an excess or a withdrawal of caffeinated drinks, such as coffee, tea, cocoa, or colas, may trigger a migraine headache. The patient should limit caffeinated sources to no more than 2 cups per day to prevent caffeine-withdrawal headaches. Some migraine headaches may be triggered by artificial sweeteners (eg, aspartame) in diet sodas.
Nitrates and nitrites
These vasodilating agents are found in preserved meats. Examples of foods containing these chemicals are lunch meats, processed meats, smoked fish, sausage, pork and beans with bacon, sausage, salami, pastrami, liverwurst, hot dogs, ham, corned beef, corn dogs, beef jerky, bratwurst, and bacon.
Monosodium glutamate
MSG is a flavor enhancer and vasodilator found in many processed foods. Food labels should be carefully checked. MSG sources include the following:
Fruit
Citrus fruits, avocados, bananas, raisins, and plums may be triggers. Although occasional individuals are sensitive to fruit, the authors encourage children with migraines to eat a well-rounded, natural (ie, avoid processed foods) diet that includes fruits and vegetables.
Over-the-counter (OTC) and prescription medications can trigger or exacerbate migraines. Excessive use of OTC pain medications and analgesics can cause occasional migraine attacks to convert to analgesic-abuse headaches or drug-induced refractory headaches. Drugs that can increase migraine frequency include the following:
Advise patients to avoid frequent or long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, triptans, or ergotamines. Naproxen sodium can be a particularly useful medication if acute therapy is needed frequently, as risk of rebound headache is lower with this agent. Advise migraine patients who have undergone prolonged treatment with amphetamines, phenothiazine, or propranolol to avoid sudden withdrawal from these medications, because migraine headaches may result.
In predisposed individuals, migraine attacks can occur as a result of psychological, physiologic, or environmental triggers; however, encourage the patient to maintain a relatively normal lifestyle by optimizing trigger factors and using prophylactic medications.
Psychological triggers include stress, anxiety, worry, depression, and bereavement. Emphasizing to the patient and family that migraine is not an imagined or psychological illness is important. Stress is not the sole cause of migraine, although it makes an underlying migraine predisposition more difficult to manage. The frequency of migraines can be reduced by maintaining a healthy lifestyle, but it cannot be eliminated.
Physiologic triggers include fever or illness, fasting, missing a meal, fatigue, and sleep deprivation. Encourage children with migraine attacks to maintain a routine with regular meal times and adequate sleep. Ice cream or cold is an interesting physiologic stimulus. Raskin and Knittle found that ingestion of ice cream caused headaches in 93% of their migraine patients. The headache typically was located at the usual site of migraine pain.
Environmental triggers of migraine include the following:
Some report that complex visual patterns such as stripes, checks, or zigzag lines may trigger migraine attacks.
Hansen et al found that the most common trigger factors reported by patients with familial hemiplegic migraine were stress, bright light, intense emotional influences, and too much or too little sleep, which are similar to the triggers associated with migraine with aura.[6]
Physical exertion can trigger childhood migraine. Some migraineurs report that they are more likely to develop a headache after participating in sports or being extremely active. Minor head trauma (eg, being hit in the head with a ball, falling on one's head) may result in exacerbations of migraine lasting from days to months. Travel or motion may cause migraine, particularly in young children.
A review of epidemiological studies on migraine and headache in children and adolescents published in the past 25 years identified a total of 64 cross-sectional studies, published in 32 different countries and included a total of 227,249 subjects. The estimated overall mean prevalence of headache was 54.4 % (95 % CI 43.1–65.8) and the overall mean prevalence of migraine was 9.1 % (95 % CI 7.1–11.1).[7]
Studies suggest that up to 5% of the pediatric population in the United States experiences migraine. Approximately one third of these children will have an aura. Approximately 20% of children with migraines develop attacks when younger than 5 years. The mean age of onset for boys is 7 years and for girls is 11 years.[8]
In prevalence study of 9000 Swedish school children, nearly 4% had migraine. The average age of onset was 6 years. The prevalence of migraine was 1.4% at age 7 years and 5.3% at age 15 years. At age 11 years, a gradual increase of migraine headache and a predominance among girls began.[9]
Migraine headaches are found in 5–10% of school-aged children. Most migraineurs begin to experience their attacks when younger than 20 years. Approximately 20% of migraine patients experience their first attack before age 5 years.
Migraine begins earlier in boys (age 7y) than girls (age 11y). From infancy to age 7 years, boys are affected slightly more often than girls.
The prevalence of migraine increases during the adolescent and young-adult years, during which 20–30% of young women and 10–20% of young men experience migraine attacks.
After menarche, a female predominance occurs and continues to increase until middle age. Migraine declines in both sexes by age 50 years.
Although migraine has long been considered a benign and self-limited condition, it can significantly impact the patient's life. The pain is often intense, and often the patient cannot concentrate or function effectively during or immediately after episodes. An estimated 65–80% of children with migraine attacks interrupt their normal activities because of the symptoms. Among 970,000 self-reported migraineurs aged 6–18 years, 329,000 school days were lost per month.
The burden of migraine may cause emotional changes such as anxiety or sadness. One study found a higher frequency of suicidal ideation in adolescents with migraine.[10]
The course and severity of migraine may be influenced by a variety of factors, including stress, depression, sleep deprivation, overuse of analgesics, and hormonal fluctuation. Appropriate diagnosis and treatment of migraine can significantly improve quality of life.
In one of the few longitudinal studies of migraine patients, Bille observed 73 children with migraine for 40 years. During puberty or young adulthood, 62% of the children were migraine free for at least 2 years; approximately 33% of these children regained regular attacks after an average of 6 migraine-free years, and a surprising 60% of the original 73 children still had migraine attacks after 30 years. In 30 years, 22% of the children never had a migraine-free year.[9]
At age 50 years, more than half the migraine group still had migraine attacks. A recall bias was found; several subjects in midlife (41%) could not remember that they experienced aura symptoms. Of those who became parents, 52% had at least 1 child in their present or previous families who developed recurrent headache, probably migrainous.
Another study assessed the 5-year follow-up outcome and possible prognostic factors of migraine subtypes with onset in childhood or adolescence. A total of 343 patients meeting the International Classification of Headache Disorders (ICHD)-II criteria for migraine without aura (MO), migraine with aura (MA), or both MO+MA (ie, 1.1, 1.2) were contacted by phone and underwent structured follow-up headache interviews. Of the original sample patients, 22.7% were headache-free at follow-up, 14.1% had a transformed headache diagnosis (tension-type headache: 8.2%, chronic daily headache: 5.8%), and 63.3% still had migraine fulfilling the criteria for ICHD-II 1.1. or 1.2, but those who were still migraineurs at follow-up were older at baseline (respectively 12.93, 9.99, and 11.02 years for MO, MA and MO+MA,P= .0005). The probability of having the same migraine subtype diagnosis at baseline and at 5-year follow-up was 55.2%, 95.1%, and 31.1% for ICHD-II 1.1, 1.2, and both 1.1 and 1.2, respectively.[11]
Because no specific diagnostic test is available for migraine, the diagnosis is made by history and examination. Elicit possible reasons for the current presentation, including past history, previous test results, allergies, and current and previous medication usage. A family history of headache should also be investigated.
The patient should describe the quality of his or her headache (eg, throbbing, pounding, squeezing, pressing, pulsating, aching, burning, lancinating, dull). Other aspects of the headache to ask about include the following:
The headache is often poorly described but is usually frontotemporal in location. Hemicranial headaches are less common in the pediatric population, particularly in younger patients.
Headaches may occur in the early morning and often awaken the child. The occurrence of these early morning headaches should not cause one to assume that the child has increased intracranial pressure.
Affected children may also experience recurrent abdominal pain without nausea, vomiting, headache, or visual symptoms. Migraine should be considered in pediatric patients with unexplained paroxysmal abdominal pain. Young children with migraine or who may be predisposed to developing migraine may have a history of motion sickness.[12]
During an attack, children appear ill and often are pale. The headache is aggravated by movement and may be associated with nausea, vomiting, photophobia, and/or phonophobia. Between attacks, children may have a dark discoloration beneath their eyes (ie, so-called migraine facies). This facial appearance is similar to that of children with an allergic diathesis (ie, so-called allergic facies).
Infants may present with only episodic "head banging." In preschool children, migraine often consists of episodes involving an ill appearance, abdominal pain, vomiting, and the need to go to sleep. They may exhibit pain by irritability, crying, rocking, or seeking a dark room in which to sleep.
In children aged 5-10 years, migraine typically has the following features:
Children of this age usually fall asleep within 1 hour of attack onset. The most common accompanying symptoms include the following:
Older children may present with a unilateral temporal headache. Many "sinus headaches" are actually of migrainous origin. The headache location and intensity often change within or between attacks.
As children mature, headache intensity and duration increase; children begin to describe a pulsating or throbbing character to the headache. Headache presentation may shift to the unilateral, temporal location characteristic of most adult migraines. Childhood migraine attacks often stop for a few years after puberty.
Nonheadache symptoms may be more distressful to young children than the headache. Younger children may experience photophobia and phonophobia without GI or headache accompaniments. Some children have recurrent bouts of nonlateralized abdominal pain without accompanying headache (abdominal migraine).
Psychiatric diseases associated with migraine can include depression, hypomania, panic attacks, anxiety disorders, or phobia.
Asthma, allergies, and seizure disorders are more common in childhood migraine patients. Preeclampsia, stroke, and hypertension are observed more commonly in adult migraine patients.
Migraine and epilepsy often occur in the same individual and may be related. Approximately 70% of patients with complex partial seizures have migraines. Most patients with migraines do not have seizures.
Migraineurs are more prone to motion sickness than are patients without migraine, and intermittent vertigo is found in 63% of patients with classic migraine and in 21% of patients with common migraine.
Cardiovascular reactivity to postural changes tends to be increased in patients with cyclic vomiting and migraine.[13] Also, diarrhea is common in migraine patients and sometimes is severe enough to result in excessive fluid loss and dehydration.
Sleep disturbances are associated with migraines, and somnambulism is found in 20–30% of migraine patients.
Visual discomfort induced by looking at striped patterns may be related to migraines; in one study, striped-pattern aversion was found in 82% of tested migraine patients.[14]
Ice cream ingestion may precipitate migraines. Raskin and Knittle found that ingestion of ice cream caused headache in 93% of migraine subjects.[15]
When evaluating a patient presenting with headache, perform a thorough general physical examination and a detailed neurologic examination. All examination findings should be completely normal.
Appropriate follow-up evaluations are necessary for patients with any of the following:
Headache may be a presenting symptom of a benign condition or a life-threatening disorder. The patient's medical history and physical examination findings often are enough to identify or exclude serious underlying processes.
Acute headache in children can result from primary and secondary disorders. Primary headaches are conditions in which there are no identifiable underlying structural or metabolic causes. Recurrent headaches usually represent primary disorders. Primary headache types include migraine, tension, chronic daily, and cluster headaches. Differentiating these headache categories is important because optimal treatment regimens vary.
Secondary headaches represent a manifestation of some underlying pathologic process. Diagnostic possibilities range from benign to life threatening and include the following:
A patient with a diagnosed primary headache disorder may also present subsequently with a secondary headache disorder.
Laboratory and imaging studies are unnecessary for the diagnosis of migraine, but they may be indicated for the exclusion of other disorders. However, only a small percentage of headache patients in whom a nonmigrainous cause is suspected require such evaluation. The differential diagnosis in a migraine patient includes the following:
A neuroimaging study typically is not necessary in adults with a chronic (>6mo) history of headaches, normal neurologic examination findings, and no seizures.
Studies have shown that children with a history consistent with migraine and normal neurologic examination findings will not have clinically significant abnormalities on head computed tomography (CT) or cranial MRI scans.[16] A small percentage of migrainous children may have incidental and unrelated findings, but routine neuroimaging is not necessary in juvenile migraine patients. However, children with chronic, progressive headaches or those younger than 4 years probably should have a cranial MRI.
Consider an imaging study in patients with a history of seizures, recent head trauma, significant change in the headache, or evidence of focal neurologic deficits or papilledema upon physical examination. No absolute rules exist in the evaluation of the headache patient; the need for a neuroimaging study ultimately is based on clinical judgment.
Electroencephalography is not useful in the routine evaluation of headache patients. Reserve it for patients with an atypical migraine aura, episodic loss of consciousness, or symptoms suggestive of a seizure disorder. Focal or diffuse background slowing can be seen during a migraine headache, particularly hemiplegic or confusional migraine; however, electroencephalography results are often normal.
Lumbar puncture is indicated if meningitis, encephalitis, subarachnoid hemorrhage, or high-low pressure syndromes are considered. Cerebrospinal fluid examination and pressure measurements are not indicated unless the history or examination findings are not consistent with juvenile migraine.
Patients in whom elevated intracranial pressure is suggested or those with focal neurologic deficits should undergo a neuroimaging study prior to a lumbar puncture.
Management of pediatric migraine has 3 facets. First, educate patients and parents concerning migraine triggers. Second, formulate a plan of treatment for the acute attacks. Third, consider prophylaxis for patients with frequent migraines. The treatment of children with mild, infrequent attacks consists primarily of rest, trigger avoidance, and stress reduction.
The first step in migraine treatment is to explain the disease to the child and the parents. The patient and parents benefit from a simple explanation of the headache pain and reassurance that it is not caused by a brain tumor or other life-threatening condition.
A regular bedtime, strict meal schedules, and avoidance of overloading the child's schedule with activities are important. Helping the child recognize migraine triggers is helpful but often difficult. Eliminating precipitating triggers reduces the frequency of headaches in some patients. Importantly, the patient must have realistic expectations; identifying and avoiding triggers reduce the frequency of migraine headaches but do not eliminate headaches.
A headache diary can be used to record unique triggers and features of the attack. Unfortunately, even the most obsessive patients and parents cannot always identify specific triggers of migraine. Advise the patient to list possible precipitating factors that occurred in the 12 hours before the attack. Other important factors include the following:
During the attack, advise the child to lie down in a cool, dark, quiet room and go to sleep at the time of the attack. Sleep is the most potent antimigraine treatment. During a migrainous attack, a child commonly can be found resting in the fetal position with the affected side of the head down.
Children should be given simple analgesics such as acetaminophen or ibuprofen. They should be taught to "give in" to their headache because activity will probably aggravate their pain. Promethazine or compazine diminishes nausea, causes drowsiness, and seems to decrease pain; therefore, it frequently is used as a rescue medication.
Some patients find that ice or pressure on the affected artery can temporarily alleviate pain. NSAIDs are effective if taken at a high, but appropriate, dosage during the aura or early headache phase. Gastric stasis occurs in most migraine patients and causes delay in absorption of oral medications. Occasionally, carbonated beverages may improve absorption.
Nonpharmacologic treatment modalities such as self-relaxation, biofeedback, and self-hypnosis may be reasonable alternatives to pharmacologic treatment in managing childhood migraine, particularly in adolescents. Response rates in children tend to be higher than in adults and show continued effectiveness over time.
Specific drugs for acute attacks include ergot preparations and triptans. Older vasoconstrictive medications (ergot preparations), such as ergotamine (Cafergot; 1mg ergotamine tartrate with 100mg caffeine), are rarely used today as rescue medications in the pediatric population.
Intravenous (IV) dihydroergotamine (DHE) is an effective abortive agent when used early in an attack and is an option for the older child. Its use in patients younger than 12 years should be questioned.
Serotonin 5-HT-receptor agonists (ie, triptans) work primarily at 2 subtypes of the serotonin receptor, 5-HT1B and 5-HT1D. Triptans are being successfully used with increasing frequency as rescue medications in young migraineurs. Several triptans are approved by the FDA for treatment of acute migraine attacks in adolescents (ie, almotriptan [Axert], zolmitriptan [Zomig Nasal Spray], naproxen/sumatriptan [Treximet]) and in children (ie, rizatriptan [Maxalt]).
Analgesic and abortive therapies are for the treatment of occasional acute headache attacks and associated symptoms. Analgesic and abortive medications should not be used frequently, because this may result in rebound headaches. In general, the earlier in an attack the pain is treated, the less severe the pain becomes. The longer the wait prior to starting therapy, the more difficult the pain is to control. Established migraines are notoriously difficult to treat successfully.
The primary goals of prophylactic drugs are to prevent migraine attacks and to reduce the frequency and severity of attacks. Half of all patients experience at most a 50% reduction in migraines. Most prophylactic migraine medications have potential adverse effects; therefore, consider only patients with 1–2 attacks per week (4 or more headache days monthly) for prophylaxis.
Possible medications for migraine prophylaxis include the following:
The FDA has approved topiramate (Topamax) for prevention of migraine headache in adolescents aged 12–17 years. It is the first such approval for this age group. The safety and effectiveness of topiramate in preventing migraine headaches in adolescents were established in a clinical trial of 103 participants. Frequency of migraine decreased by approximately 72% in treated patients compared with 44% in participants receiving placebo.[17, 18] However, a multicenter, randomized trial of amitriptyline 1 mg/kg/day, topiramate 2 mg/kg/day, and placebo in individuals 8 to 17 years of age with migraine did not demonstrate significant efficacy of either amitriptyline or topiramate over placebo in reducing headache days over a period of 24 weeks. There were also higher rates of adverse events in the amitriptyline and topiramate groups than in the placebo group.[19]
Calcium channel blockers had been used for migraine prophylaxis in children, but results have been inconsistent.
Initially administer drugs at very low dosages and slowly titrate to therapeutic efficacy. This approach lessens adverse effects and results in better long-term patient compliance. Often, several weeks are necessary before therapeutic gains are observed. No consensus exists on the duration of prophylactic medication usage, although most neurologists aim for 3-6 months of good symptom control.
Some patients must be maintained on long-term prophylactic therapy, and others tolerate drug holidays, particularly during summer when migraine attacks are less frequent for many children. Occasionally, prophylactic drugs are effective initially but become ineffective over the long term. Subsequent prophylaxis with the same agent often is not as effective. Withdraw drugs slowly to prevent relapse and withdrawal symptoms.
Some forms of familial hemiplegic migraine respond to acetazolamide, and children with abdominal migraine respond to typical migraine prophylactic medication. Some children with cyclic vomiting respond to antimigraine drugs (eg, propranolol, amitriptyline, cyproheptadine, sumatriptan). However, these children often experience severe fluid and electrolyte disturbances that require IV fluid therapy.
Aggressive therapy is needed but can often be administered in an outpatient infusion center. There are 5 principles of treatment: hydration, analgesia, specific antimigraine medication, antiemetics, and sedation.
Since vomiting and poor intake are almost always present, treatment begins with rehydration using glucose-containing fluids. An IV bolus of normal saline or lactated Ringer's solution followed by infusion of 5–10% dextrose solution should be considered.
Analgesic options should include relatively mild pain medications such as intramuscular (IM) ketorolac or rectal suppositories of naproxen or indomethacin. If possible, narcotics should be avoided.
First-line, migraine-specific regimens include triptans, IV valproic acid (Depacon), and IV DHE; however, these agents should not be used together. In addition, the use of IV DHE in patients younger than 12 years is questionable; in this age group, many patients respond to IV fluids and lorazepam. Subcutaneous (SC) sumatriptan (0.06mg/kg, maximum dose 6mg) may be useful in patients unable to tolerate oral medications.
Similarly, in patients weighing less than 50kg, be sure to appropriately titrate the dose of IV medications.
An adult-sized patient can be pretreated with 0.5–1mg of lorazepam. IV fluids can be administered concurrently; hydration often is helpful. After 15–30 minutes, the patient is then administered 0.5mg of haloperidol to prevent nausea. This is followed in 30 minutes by 0.5mg of DHE. In many patients, the headache is aborted or significantly relieved with this protocol.
Patients with persistent status migrainosus can be admitted to the hospital; therapy may be repeated every 8 hours for up to 48 hours. In one study, 49 of 55 DHE-treated patients became headache free within 48 hours, and 39 of these patients sustained the benefits for a mean follow-up period of 16 months.
Clinical observations have suggested that IV prochlorperazine[20] (5-10mg) or metoclopramide (10mg) followed by 0.1–0.5 mg of IV DHE may be effective. Dosage is age dependent and may be repeated in 1 hour if needed. An alternative is to give an IV bolus of valproate (20–30mg/kg) followed by a continuous infusion of 1–2mg/kg for 24 hours.
Finally, sedation is an important component of treatment, especially in refractory cases. Sleep has long been recognized as beneficial in migraine. IV diphenhydramine (25–50mg) can be effective and should be considered when metoclopramide is the antiemetic of choice. IV benzodiazepines have sedative and anxiolytic properties and therefore are also useful in migraine status.
If headaches cannot be reasonably controlled within 6 months, consider consulting a pediatric neurologist. In addition, refer children with a new onset of neurologic deficits to a pediatric neurologist.
In August 2019, the American Academy of Neurology (AAN) and American Headache Society issued new guidelines on preventing and treating migraine in children.[21, 22]
Recommendations for migraine prevention include the following:
Recommendations for acute treatment include the following:
Instruct patients, preferably during office visits rather than in the emergency department, to identify triggers.
Ask patients to make a follow-up appointment if the headaches worsen, if they do not respond to medications, or if adverse effects are intolerable. Several medication trials often are necessary before adequate headache control is achieved.
Patients should have realistic expectations; while pharmacotherapy lessens the impact of migraine, it does not eliminate the underlying pathology.
For patient education information, see the Headache and Migraine Center, as well as Causes and Treatments of Migraine and Related Headaches, Migraine Headache in Children, and Understanding Migraine and Cluster Headache Medications.