Background: Migraines are severe, throbbing headaches frequently located in the temples or frontal head regions. In children, the headaches are often bilateral, and 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 the youngest children. Patients avoid bright lights, loud noises, and strong odors. Relief typically is associated with sleep. The initial physician evaluation focuses on excluding other serious medical conditions. Treatment consists of identifying trigger factors in the environment, providing acute pain relief, and considering prophylaxis.
Migraine is a common disorder among the young. Estimates indicate that 3.5-5% of all children will experience recurrent headaches consistent with migraine. As in adults, most children (approximately 64%) have migraine without aura. Approximately 18% have only migraine with aura, 13% have both, and 5% experience only aura. Headaches are chronic, typically severe, and often associated with autonomic dysfunction. The pain is throbbing, is located in the trigeminal nerve distribution, is frequently accompanied by GI symptoms, may be hemicranial, and is often associated with photophobia and phonophobia. Head pain is aggravated by movement and is relieved by sleep.
Several conditions that are relatively common among the pediatric population are thought to be variations and/or precursors of migraine. These include (1) benign paroxysmal vertigo, (2) cyclic vomiting, (3) paroxysmal torticollis, and (4) transient global amnesia (rare in children).
Migraine types
Migraine with aura (classic migraine)
Migraine with aura is a severe, often throbbing, generalized or hemicranial headache that is preceded by an aura that is typically visual. Approximately one third of children have migraine with aura. 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 5-20 minutes. Other less common auras consist of sensory symptoms or focal motor deficits (hemiplegia). Approximately 5% of affected children have aura without headache.
Migraine without aura (common migraine)
Approximately 60% of children with migraine do not experience an aura. These headaches are usually associated with nausea, vomiting, or both. They are frequently accompanied by sensitivity to light, sound, and movement. If untreated, these headaches can last up to 72 hours. In children, the duration of head pain is typically less than in adults and usually lasts less than 4 hours.
Complicated migraine
This is a migraine attack associated with neurologic signs or symptoms that persist beyond the head pain. Examples include hemiplegic migraine and ophthalmoplegic migraine, which is a rare disorder characterized by a severe unilateral headache associated with prolonged ocular nerve palsies. With the ophthalmoplegic migraine, the oculomotor nerve is typically involved and recurrent attacks may cause a permanent deficit.
Basilar migraine (Bickerstaff migraine)
This disorder is usually seen in adolescent females. Head pain is occipital and associated with at least 2 auras consistent with brainstem, occipital, and/or cerebellar dysfunction, such as ataxia, hearing disturbance, altered consciousness, diplopia, dizziness, dysarthria, tinnitus, visual disturbance, drop attacks, paresthesias, and weakness.
Confusional migraine
This type of migraine is uncommon and usually occurs early in the second decade of life. Attacks are sometimes precipitated by minor head trauma and are characterized by the rapid development of confusion and agitation. Affected children are delirious, restless, combative, and appear in pain but do not complain of headache. 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. These confusional attacks tend to recur but are eventually replaced by typical migraine.
Pathophysiology: No one theory can explain all the symptoms of a typical migraine headache. Models of headache pain include trigeminovascular or brainstem processes. Migraine also may be an expression of neuronal hyperexcitability. Intracellular magnesium deficiency, nitric oxide (NO), calcium channelopathies, or mitochondrial disorders may trigger attacks. The pathogenesis of migraine is poorly understood. Migraine is probably most accurately considered a heterogeneous disorder. Multiple different mechanisms may be involved in its pathogenesis.
Substances that may precipitate an attack 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.
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).
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.
Vascular theory
Models that explain the characteristic sensory disturbances in migraine with aura include the vascular theory and cortical-spreading depression. The vascular theory views migraine as a defect of the CNS vasculature. Early observers noticed that pulsations of the superficial temporal artery were reduced after ergotamine administration. Excessive intracranial arterial vasoconstriction was believed to produce focal ischemia and aura symptoms. Brain acidosis and vasodilatation resulting in stretching of pain fibers in the arterial walls were believed to cause the throbbing quality of the headache.
This classic vascular theory suggests that a migraine attack consists of 2 phases. The first, or prodromal, phase is reportedly characterized by arterial vasospasm with resultant cerebral ischemia and the potential for transient neurologic signs and symptoms. The second phase consists of intracranial and extracranial vasodilatation, which produces the pulsating pain.
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.
Cortical-spreading depression
The vascular theory has been replaced by the neuronal theory, which suggests that migraine with aura is related to the paroxysmal depolarization of cortical neurons. According to this theory, the initial phase is the result of a wave of spreading cortical depression, which is associated with depression of spontaneous EEG activity. The cortical depression begins in the occipital head 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.
Cortical-spreading depression may best explain the sensory disturbances during the migraine aura. In the brain, a brief period of intense spike activity is followed by a prolonged depolarization wave that moves across the cortical gyri at 2-3 mm/min, resulting in decreased spontaneous and evoked neuronal activity. 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.
Involvement of serotonin
Another neurogenic cause for both the headache and aura phases of migraine involves the neurotransmitter serotonin (5-hydroxytryptamine). Serotonin 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 causes a wave of spreading excitation followed by depression of neuronal activity.
During an attack, urine levels of the serotonin metabolite hydroxyindoleacetic acid are increased significantly in migraineurs. At the onset and for the duration of the headache, intraplatelet serotonin levels decrease. Serotonin is released from platelets at the onset of an attack. During a migraine attack, serotonin turnover is also reduced. Migraineurs, however, have increased synthesis of serotonin between attacks.
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.
Sterile inflammation process
Investigators also have proposed that a sterile inflammation 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.
Nitric oxide
NO recently was found to cause cerebral arterial dilation and a delayed headache in migraineurs; however, it does not cause an aura.
NO regulates blood pressure, inhibits platelet function, and acts as a neurotransmitter. It is involved in the central processing of pain and the regulation of vasodilatation in the CNS and is produced by NO synthase in neurons. NO donator agents (eg, nitroglycerin, glyceryl trinitrite, isosorbide) cause migrainelike pain after 3-10 hours. Monomethyl-L-arginine, a specific inhibitor of NO synthase, is an effective treatment for migraine pain.
Calcium channelopathy
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 the known FHMs studied have linkage to 19p13. Different missense mutations (R192Q, T666M, V714A, I1811L, G4644T) cause FHM with different phenotypic accompaniments. Linkage to a separate gene on chromosome 1 also occurs. An estimated 5% of migraineurs may carry a mutation in the calcium channel gene.
Mitochondrial dysfunction
Many migraine families demonstrate a predominant maternal inheritance pattern that may be caused by a mitochondrial dysfunction. Both migraine with aura and migraine without aura are 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 (400 mg/d) 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.
Frequency:
· In the US: The 1-year prevalence rate among males is 6% and is 14-18% among females. The median frequency of attacks is 1.5 events per month. The median duration is 24 hours, with 20% lasting 2-4 days. Approximately 5% of the US population experiences 18 or more days of migraine per year. Estimates indicate that at least 2.5 million individuals in the United States have at least 1 day of migraine per week. Among the young, studies suggest that up to 5% of the pediatric population experience juvenile migraine. Approximately one third of children will have an aura. Approximately 20% of children develop attacks when younger than 5 years.
· Internationally: In one of the few longitudinal studies of migraine patients, Bille observed 73 children with migraine for 40 years. The average age of onset was 6 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.
Mortality/Morbidity: Although migraine has long been considered a benign and self-limited condition, it can significantly impact the patient's life. The pain is 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. Appropriate diagnosis and treatment of migraine can significantly improve quality of life.
Sex:
· Migraine begins earlier in boys than in girls. From infancy to 7 years, boys are affected equally or slightly more 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.
Age:
· Migraine headaches are a common problem in children and 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 when younger than 5 years. 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.
· Young patients with migraine (5-10 y) experience bilateral frontal, bilateral temporal, or retro-orbital headache; nausea; abdominal cramping; vomiting; photophobia; phonophobia; and a need to sleep. They usually are asleep within 1 hour of attack onset. The most common accompanying symptoms include pallor with dark circles under the eyes, tearing, swollen nasal passages, thirst, swelling, excessive sweating, increased urination, and diarrhea. Older children tend to 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 and they develop migraine attacks with similar periodicity. They also describe a pulsating or throbbing character to the headache. Headache presentation often shifts to the unilateral, temporal location that is 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. Patients who eventually develop migraine with aura present earlier than patients who experience migraine without aura.
History: Headache may be a presenting symptom of a benign or a life-threatening condition. The patient's medical history and physical examination findings often are enough to identify or exclude serious underlying processes. Because no specific diagnostic test is available for migraine, make the diagnosis on the basis of history findings, physical examination findings, and clinical judgment. Elicit reasons for the current presentation, including past history, previous test results, allergies, and current and previous medication usage. The patient should describe the headache quality (eg, throbbing, pounding, squeezing, pressing, pulsating, aching, burning, lancinating, dull), location, timing, severity, precipitating events, duration, and heredity.
Disorders that cause acute headache in children include both primary and secondary disorders. Primary headaches are conditions in which the headache is the medical condition and no underlying structural or metabolic cause is present. Treatment is aimed at the specific headache disorder. Primary headache types include migraine, tension, chronic daily, and cluster headaches. Differentiate these headache categories because optimal treatment regimens vary. Recurrent headaches usually represent primary disorders.
Secondary headaches represent a manifestation of some underlying pathologic process that alleviates the headache when treated. Secondary headaches can herald a wide range of diagnostic possibilities from benign to life threatening, including intracranial and extracranial infections, intracranial mass lesions, head or neck trauma, febrile illness (eg, influenza), meningitis, encephalitis, sinusitis, dental abscess, subarachnoid hemorrhage, and hypertension. A patient with a primary headache disorder also may present with a secondary headache disorder at subsequent visits.
Migraine is a relatively common condition among the young, affecting up to 5% of the pediatric population. Approximately 20% of patients have attacks before age 5 years. 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.
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. 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. Infants may present with only episodic "head banging.” Young children with migraine or who may be predisposed to developing migraine may have a history of motion sickness.
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).
· Phases of a migraine attack: A migraine attack has 4 potential phases that are important to recognize and describe.
o Premonitory phase or prodrome: Both migraine with aura and migraine without aura have a premonitory phase that may precede the headache phase by up to 24 hours. During this phase, irritability, elation or sadness, talkativeness or social withdrawal, an increase or decrease in appetite, food craving or anorexia, water retention, and/or sleep disturbances 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, which are difficult to explain to their parents or physicians.
o Aura: An aura is a focal cerebral dysfunction that immediately precedes or coincides with the headache onset. The aura may manifest without headache or may be more severe than the subsequent 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 5-20 minutes. Motor auras tend to last longer than other forms of aura.
Children are often unaware or unable to describe their aura; pictorial cards that illustrate typical visual aura may aid in obtaining an accurate history. The visual aura is the most common form in children, consisting of blurred vision, fortification spectra (zigzag lines), scotomata (field defects), scintillations, black dots, kaleidoscopic patterns of various colors, micropsia, macropsia (distortion of size), and metamorphopsia ("Alice in Wonderland" syndrome). Visual auras are often reported as moving or changing shapes; other auras include attention loss, confusion, amnesia, agitation, aphasia, ataxia, dizziness, vertigo, paraesthesia, or hemiparesis. Aura symptoms vary widely within and between attacks.
o Headache: The actual headache phase of the migraine attack is usually shorter in the pediatric population compared with adults; pediatric headaches can last 30 minutes to 48 hours, but they usually last less than 4 hours. Some young patients report short headaches lasting 10-20 minutes. Coughing, sneezing, climbing stairs, or bending over increases headache pain by increasing intracranial pressure. Childhood migraine headaches are often less severe than adult migraine headaches. The headache phase is often associated with cold extremities, nausea, anorexia, vomiting, diarrhea, increased urination, constipation, dizziness, chills, excessive sweating, ataxia, numbness, photophobia, phonophobia, memory loss, or confusion.
o Postdrome: 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.
· Types of migraines: A patient may experience varying types of headaches, including different forms of migraine. The 2 most frequent forms are common migraine and classic migraine. Complicated migraines, migraine equivalents, and migraine variants also occur and are differentiated by patient history.
o Migraine with aura: Classic migraine (migraine with aura) is characterized by a visual aura followed by a unilateral throbbing headache, which may later generalize to both sides. It lasts between 30 minutes and 48 hours. Headaches usually occur 1-2 times per month but the frequency may vary considerably among individuals.
o Common migraines: Common migraines lack an aura. Migraine without aura in children is traditionally described as a recurring bilateral headache disorder with a throbbing and/or pulsating pain quality, moderate-to-severe intensity, and severe GI symptoms. It is aggravated by physical activity and relieved by sleep. Common accompanying symptoms in children are irritability and pallor with dark circles under the eyes. The presentation in young children is more often bilateral, orbital, or frontotemporal, and the pain may radiate to the face, occiput, or neck. Migraine without aura occurs in 60-85% of migrainous children.
o Status migrainosus: Status migrainosus is a severe form of migraine in which the headache attack is continuous over 72 hours. Patients usually have a preexisting migraine history. In those who vomit, rehydration is often the necessary first step. An effective treatment is intravenous dihydroergotamine (DHE) with an antiemetic.
o Complicated and variant migraines: These are classified as migraines because they often have the same triggers. They are brief, recurrent, episodic disorders that are intensified by movement and are relieved by deep sleep or typical migraine medications.
Complicated and variant migraines have some of the same symptoms as typical migraines, including pain, GI syndromes, autonomic symptoms, neurologic symptoms, and changes in mood or emotion. Debate exists regarding whether these disorders are migrainous or nonmigrainous. These usually benign disorders are frightening because they mimic life-threatening emergency situations.
Migraine equivalents are underrecognized and underreported manifestations of childhood migraine. They are often forerunners of the typical migraine, and complicated and variant migraines occasionally alternate with typical migraine symptoms. Complicated migraine has dramatic focal features and a persistent neurologic deficit that remains for at least 24 hours after the headache.
o Familial hemiplegic migraine: FHM is an autosomal dominant form of migraine with aura. Patients have 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 as long as a week.
The headache is usually contralateral to the hemiparesis. Some FHM attacks are associated with cerebellar ataxia. Other types of severe FHM may manifest with coma, fever, and meningismus. A third type of FHM involves progressive ataxia, nystagmus, gait unsteadiness, limb incoordination, and dysarthria. Some forms of FHM respond to acetazolamide. 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.
o Basilar migraine (basilar artery migraine or Bickerstaff syndrome): Basilar migraine 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 brain stem, occipital cortex, and cerebellum. The occipital headache must have at least 2 of the aura symptoms listed below, which are associated with dysfunction originating from the occipital and/or brainstem area.
§ Ataxia
§ Bilateral paresthesias
§ Deafness
§ Decreased level of consciousness
§ Diplopia
§ Dizziness
§ Drop attacks
§ Dysarthria
§ Fluctuating low-tone hearing loss
§ Tinnitus
§ Unilateral or bilateral vision loss
§ Vertigo
§ Weakness
A history of typical migraine exists in 86% of families studied. Many patients experience basilar migraine attacks intermingled with typical migraine attacks.
o Ophthalmoplegic migraine: This form of migraine is rare. It is characterized by a severe unilateral headache with prolonged oculomotor nerve palsies involving the third, fourth, or sixth cranial nerves. Ophthalmoplegia may precede, accompany, or follow the headache; recurrent episodes may cause permanent oculomotor deficit.
o Ophthalmic (retinal) migraines: These migraines involve repeated attacks of monocular scotoma or blindness usually followed by headache. The patient must have normal ophthalmologic examination findings between attacks. Exclude a retinal embolism or abnormality.
o Benign paroxysmal vertigo of childhood: 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.
o Acute confusional migraine: This type of migraine is characterized by transient episodes of amnesia, acute confusion, agitation, lethargy, and dysphasia precipitated by minor head trauma. 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. The patient usually recovers within 6 hours. 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 MRI results should be normal.
o Migraine-associated cyclic vomiting syndrome (periodic syndrome): This syndrome is characterized by recurrent periods of intense vomiting separated by symptom-free intervals. 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 6-48 hours. Associated symptoms include abdominal pain (80%), nausea (72%), retching (76%), anorexia (74%), pallor (87%), lethargy (91%), photophobia (32%), phonophobia (28%), and headache (40%).
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 beg...
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