Background: Migraine is a recurrent, intermittent headache syndrome and commonly occurs in young children. The headache is severe and throbbing; during episodes, the child often looks ill and pale. Relief typically is associated with sleep. Initial evaluation focuses on excluding other serious diseases or conditions. Treatment consists of identifying trigger factors in the environment, providing acute pain relief, and considering prophylaxis.

Migraine presents with various neurologic and nonneurologic symptoms that are exacerbated with routine physical activity and relieved by sleep. An otherwise healthy child has periodic short episodes of severe head pain that often are reversed completely by deep sleep. Recurring spells of vomiting, abdominal pain, or dizziness may be juvenile forms of migraine.

The heterogeneity of this disorder can make migraine difficult to diagnose. An inherited physiologic predisposition is believed to render the individual more likely to experience a migraine after some minor trigger. The key element in recognizing this disorder is identifying a pattern of short illness episodes that are separated by symptom-free intervals and are relieved by sleep. Migraineurs are easy to identify in a crowd; they typically wear sunglasses indoors because of sensitivity to bright fluorescent lights.

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.

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 central nervous system (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.

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

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). 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. An injection of serotonin during an attack decreases migraine symptoms but is associated with many unpleasant side effects. Many migraine drugs are serotonin-receptor agonists or antagonists.

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 like 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 1 A 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 6. One half of 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 have 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 the attack frequency by 56%. The full benefit is obtained after 3 months. Riboflavin was postulated to improve the altered mitochondrial energy metabolism. It is probably most accurate to think of migraine as a heterogeneous disorder. Multiple different mechanisms may be involved in its pathogenesis.

Frequency:

In the US: Migraine occurs in 5-10% of school-aged children. Prevalence increases constantly during childhood and adolescence. Migraine prevalence reaches a peak at approximately 44 years. Spontaneous remission occurs in many patients.

Internationally: In one of the few longitudinal studies of migraine patients, Bille observed 73 children with migraine for 40 years.

The average onset occurred at 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 migraines after 30 years. In 30 years, 22% of the children never had a migraine-free year.

Mortality/Morbidity: Although migraine long has been considered a benign and self-limited condition, it can impact the patient's life significantly. 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 migraines 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 improve quality of life significantly.

Sex:

Migraine begins earlier in boys than in girls. From infancy to 7 years, males are affected equally or slightly more than females.

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 migraines.

After menarche, a female predominance occurs and continues to increase until middle age. Migraine declines in both sexes by age 50.

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 increases and they develop migraines with similar periodicity. They also describe a pulsating or throbbing character of the headache. Headache presentation often shifts to the unilateral, temporal location that is characteristic of most adult migraines. Childhood migraines 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 gastrointestinal (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 often are enough to identify or exclude serious underlying processes. Since no specific diagnostic test for migraine exists, make the diagnosis through the history, physical exam, and clinical judgment. Elicit reasons for the current presentation, including past history, previous tests, allergies, and current and previous medications. 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 headache, and cluster headaches. Differentiate these headache categories, since 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 primary headache disorder also may present with a secondary headache disorder at subsequent visits.

Phases of a migraine attack: A migraine attack has 4 potential phases that are important to recognize and describe.
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 often are 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.

Aura: An aura is a focal cerebral dysfunction that immediately precedes or coincides with the headache onset. The aura may present 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 often are 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 often are 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.

Headache: The actual headache phase of the migraine attack usually is shorter in the pediatric population compared to 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. The severity of childhood headache often is milder than adult migraines. The headache phase often is associated with cold extremities, nausea, anorexia, vomiting, diarrhea, increased urination, constipation, dizziness, chills, excessive sweating, ataxia, numbness, photophobia, phonophobia, memory loss, or confusion.

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.

Common migraines: Common migraines lack an aura. Migraine without aura in children traditionally is 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 front temporal, and the pain may radiate to the face, occiput, or neck. Migraine without aura occurs in 60-85% of migrainous children.

Status migrainosus: Status migrainosus is a severe form of migraine in which the headache attack is continuous over 72 hours. Patients usually have a pre-existing migraine history. In those who vomit, rehydration is often the necessary first step. An effective treatment is intravenous (IV) dihydroergotamine (DHE) with an antiemetic.
Complicated and variant migraines 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 often are 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.

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 usually is contralateral to the hemiparesis. Some FHM is associated with cerebellar ataxia. Other types of severe FHM may present 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.

Basilar migraine (basilar artery migraine or Bickerstaff syndrome): Basilar migraine is a subtype of migraine with aura. It mostly 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.

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.
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.

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 often are identified clearly in the patient's history. Examples of triggers include cheese, chocolate, monosodium glutamate (MSG), emotional stress, excitement, or infections. Usually a family history of migraines in the parents or siblings is present. Some children with cyclic vomiting respond to antimigraine drugs such as propranolol, amitriptyline, cyproheptadine, or sumatriptan. These children often experience severe fluid and electrolyte disturbances that require intravenous fluid therapy. Cyclic vomiting syndrome is a diagnosis of exclusion.

Differentiate cyclic vomiting related to migraine from nonmigraine cyclic vomiting conditions. Other causes of cyclic vomiting include GI disorders (malrotation), neoplasms, urinary tract disorders, metabolic and endocrine disorders, and mitochondrial DNA deletions. 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 strong maternal history is associated with mutations of the mitochondrial DNA. When mitochondrial mutations are suggested, obtain plasma lactate and urine organic acids during an attack.

Abdominal migraine: The patient may suffer from 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. These children respond to typical migraine prophylactic medication.

From:   http://www.emedicine.com/neuro/topic529.htm