eMedicine Specialties > Neurology > Pediatric Neurology

Childhood Migraine Variants

Wendy G Mitchell, MD, Professor of Neurology, University of Southern California School of Medicine; Consulting Staff, Division of Child Neurology, Children's Hospital Los Angeles, Los Angeles County-University of Southern California

Updated: Feb 5, 2009

Introduction

Background

Migraine in children may be similar to adult presentations and include headache, with or without aura, accompanied by nausea, vomiting, photophobia, and relief with sleep. However, several variations of migraine are unique to children and rarely if ever occur in adults. Migraine may present with prominent nonheadache symptoms in young children (migraine without headache), or neurologic symptoms (aura) may be much more prominent than the headache.

Various recognized childhood syndromes assumed to be pathophysiologically related to migraine include benign paroxysmal vertigo of childhood, abdominal migraine, cyclic vomiting of childhood, and acute confusional migraine (acute confusional state). Basilar migraine (particularly in adolescent girls) may present with prominent dizziness and near-syncope and/or syncope with or without a subsequent headache. Hemiplegic migraine (usually an autosomal dominant disorder) may present in early childhood and occasionally may continue into adulthood. Ophthalmoplegic migraine also may occur in childhood.

Pathophysiology

Although migraine and variants of migraine have long been assumed to have a vascular etiology, increasing evidence points to underlying primary neurologic causes. Some forms of migraine are genetic. Specific markers on chromosome 19 were found in some families with hemiplegic migraine.

Mitochondrial abnormalities, either from autosomal or mitochondrial DNA, may contribute particularly to the cyclic vomiting syndrome.

Sex

• In contrast to female predominance in adults, the overall frequency of migraine headaches in childhood is slightly higher in boys than in girls.
• Frequency of migraine variants is not known to vary between the sexes.

Age

Benign paroxysmal vertigo of childhood, sometimes considered a migraine variant, generally presents in toddlers.

Acute confusional migraine generally presents in the elementary school years. Less commonly, children can present either in the preschool years or in early adolescence. First attacks during the postpubertal teenage years are rare, although episodes may continue beyond puberty.

Hemiplegic migraine may present in early childhood. Basilar migraine, particularly with syncope, often presents in the early teenage years.

Clinical

History

Variant migraine episodes may be independent of actual head pain. Other symptoms may predominate and be significantly more troublesome.

• Hemiplegic migraine
  • Hemiplegic migraine presents with hemiplegia or hemiparesis, with or without a speech and/or language disturbance, which clears in minutes to hours.
  • Headache may be less dramatic than the hemiplegia. Other migrainous symptoms such as nausea, vomiting, and photophobia are present variably. Hemiplegia may precede or accompany the headache.
  • This variant is often familial, dominantly inherited, and linked to chromosome 19 in some studies. An alternative locus has been described on chromosome 1. A defect in the gene for the calcium channel is documented in some families (affecting the voltage-dependent P/Q-type calcium channel alpha-1A [CACNA1A] subunit). An increased risk of stroke exists in families with this disorder. Cerebral autosomal dominant arteriopathy and subcortical infarcts and leukoencephalopathy (CADASIL), an autosomal dominant disorder in which multiple subcortical strokes may lead to dementia in early adulthood, sometimes presents in adolescence as atypical hemiplegic migraine. The CADASIL mutation also localizes to chromosome 19.
  • Diagnosis cannot be made during the first episode, although it may be suspected in the presence of a positive family history. Exclude more serious causes of headache with hemiplegia and/or hemiparesis including intracranial hemorrhage, mass, infection, or stroke. With repeated stereotyped episodes and complete clearing between episodes, the diagnosis can be made with more confidence, particularly in the presence of a positive family history.
  • Differential diagnosis of repeated episodes includes alternating hemiplegia of childhood, unobserved partial seizures with postictal paralysis, and mitochondrial cytopathies, particularly the mitochondrial encephalomyopathy, lactic acidosis, and stroke syndrome.
• Confusional migraine
  • Although this variant is more common in younger children, it sometimes presents in postpubertal adolescents or adults. Occasionally, a child whose episodes began in the prepubertal years continues to have episodes into adolescence. The child has a period of confusion and disorientation, with or without agitation, followed by vomiting, which is relieved by sleep. Headache may not be prominent or may be elicited only retrospectively.
  • Making the diagnosis during the first episode is difficult, and it can be made only after the episode has resolved fully.
  • Acute differential diagnosis of a single episode includes all types of encephalopathy and/or encephalitis, toxic ingestion, intoxication, and/or an unobserved seizure with postictal agitation.
• Abdominal migraine
  • The child may complain of episodic pain, nausea, and vomiting. The headache may be minimal or absent. An aura may precede the pain but is not frequent. Symptoms are relieved by sleep and antiemetic and/or antimigraine therapies.
  • Cyclic vomiting of childhood, which can be associated with a mitochondrial cytopathy, may be a severe variant of abdominal migraine.
  • Diagnosis is difficult to make during the first episode.
• Basilar migraine
  • The patient may have an aura followed by dizziness, vertigo, syncope, and dysarthria. Headache may be minimal or absent.
  • It is observed most frequently in adolescent girls.
  • Differential diagnosis includes cardiogenic or vasovagal syncope, inner ear disease, and posterior fossa tumors.
• Migraine aura without headache
  • Migraineurs of any age may experience an aura with or without the typical headache. In some, the headache may be minimal while neurologic symptoms predominate.
  • Visual symptoms without subsequent headache are fairly frequent. These include scintillating scotomata, formed visual hallucinations (usually stereotyped, in a single visual field), micropsia, and tunnel vision.
  • Differential diagnosis includes occipital epilepsy, with or without an identifiable lesion. If episodes never are accompanied by headache, the diagnosis is speculative.
  • Auditory hallucinations as migraine auras are infrequent but can occur.
  • Sensory dysesthesias (usually hemisensory numbness and/or tingling) similar to more typical migraine aura may occur without subsequent head pain.
• Benign paroxysmal vertigo of childhood
  • Based on a high proportion of children with a family history of migraine, it is sometimes considered a migraine variant. This syndrome is not uncommon and frequently is followed by the development of more typical migraine headaches later in childhood.
  • This syndrome presents with brief episodes of vertigo.
  • Toddlers may be unable to verbalize the symptoms but typically cling to the parent and look frightened.
  • Older children often verbalize that they are "moving."
  • Headache does not follow the attack.
• Ophthalmoplegic migraine
  • This migraine variant may begin in childhood.
  • Acute disorders of eye movement, unilateral abnormal pupillary response, or Horner syndrome may precede or accompany the headache.

Physical

• Typically, as with all vascular headache syndromes, the neurologic examination between episodes is completely normal.
• If persistent neurologic signs (eg, hemiparesis, visual changes, sensory loss) are evident between episodes, strongly consider and investigate alternative diagnoses.

Causes

• Migraine, in general, may have a genetic predisposition with environmental and systemic triggers.
• Hemiplegic migraine may be autosomal dominant.
• Mitochondrial abnormalities (maternally inherited via mitochondrial DNA, recessively inherited via chromosomal DNA, sporadic) may account for some cases of abdominal migraine or cyclic vomiting of childhood.
• In subjects with mitochondrial disorders, fasting or systemic stress such as fever or illness may precipitate episodes.

Differential Diagnoses

Other Problems to Be Considered

Alternating hemiplegia of childhood
Benign occipital epilepsy of childhood
CADASIL, for alternating hemiplegias presenting in adolescents
Complex partial status epilepticus
Epilepsy: pediatric overview
Ingestions
Intoxications
Organic acidurias

Workup

Laboratory Studies

• During the first or worst episode, perform appropriate laboratory and neuroradiologic studies to exclude other causes of the symptoms.
• Laboratory studies generally are not helpful between episodes when a history of multiple, recurrent episodes and complete clearing between episodes exists.
• Evaluate a child with cyclic vomiting with or without head pain for metabolic disease, particularly mitochondrial cytopathy.
  • Studies performed during attacks have higher yield than those performed while the child is feeling well.
  • During the attack, perform the following investigations: serum lactate, serum pyruvate, urine organic acids, and serum ammonia samples. Samples must be collected carefully and handled appropriately by the laboratory. If suspicion of mitochondrial cytopathy is high, blood may be collected any time to examine the DNA for mitochondrial point mutations and deletions.
• For aura without headache, the differential diagnosis often includes simple partial (focal) seizures. Therefore, electroencephalography (EEG [sleep-deprived is possible] or video EEG [if episodes are frequent]) may help in the diagnosis.
• For other migraine variants, EEG generally does not confirm or exclude migraine or other alternatives, since epileptiform EEG changes can be observed in migraineurs.

Imaging Studies

• Neuroimaging (CT, MRI) is indicated during the first or worst attack that presents with simultaneous focal neurologic deficits or altered mental status and/or if any focal findings persist between attacks. Perform these studies to exclude other acute causes of the symptoms. Neuroimaging is less important if the patient presents during a symptom-free interlude, with a history of multiple attacks with complete recovery. In these patients, the clinician can usually rule out acute, life-threatening conditions and more reasonably make a diagnosis of migraine based on history.
• During or immediately after an attack, functional neuroimagingmay support the diagnosis, although migraine is most often a clinical diagnosis.
  • Single photon emission computed tomography may show hypoperfusion during an aura or episode.
  • Functional MRI (fMRI), a research technique, also may demonstrate abnormalities of perfusion.
  • Gadolinium-enhanced MRI may show focal enhancement during or immediately after the attack. This can cause confusion with ischemic stroke, inflammatory conditions, or infection.

Other Tests

• EEG may be abnormal during or immediately after an episode, with slowing in focal or generalized patterns. In general, nonspecific interictal EEG abnormalities, including epileptiform activity, are reported in higher frequencies in migraineurs.
• Continuous ambulatory or video EEG may be useful in the rare patient with episodic confusion, hallucinations, or focal neurologic deficits; partial seizures or nonconvulsive status epilepticus are included in the differential diagnosis for the attack.

Treatment

Medical Care

The first step in treatment is to establish the diagnosis. When attacks have occurred on multiple occasions, with complete resolution between attacks, particularly in the presence of a positive family history of migraine, extensive laboratory evaluations and imaging can be avoided. When the child is first seen acutely, particularly during the first episode, more extensive evaluation may be necessary to exclude alternative diagnoses. Treatment can be divided into the short-term care of the specific attack and long-term medication to reduce severity or frequency of episodes. Notably, no agents have adequate clinical trials to establish safety and efficacy for either relief or prevention of migraine in preadolescent patients. All treatment is based upon weaker, often anecdotal evidence.

• Hemiplegic migraine
  • Acute treatment: Antiemetics, mild sedatives, and nonnarcotic pain relievers are generally safe. However, vasoconstrictors, triptans, and ergotamine preparations are contraindicated.
  • Chronic prevention: Any of the agents used to prophylax migraine have been used for hemiplegic migraines; beta-blockers, low-dose tricyclics, low-dose daily aspirin (stopping during febrile illnesses), low-dose anticonvulsants, and calcium channel blockers can be administered. Flunarizine, a calcium channel blocker not available in the US, is probably the most effective agent for true alternating hemiplegia of childhood. Nonprescription alternative agents sometimes used for prevention include high-dose riboflavin, with or without magnesium supplementation, with or without herbals (feverfew).
• Cyclic vomiting of childhood
  • Acute treatment: If mitochondrial cytopathy or organic aciduria is suggested or diagnosed, tailor treatment to the underlying disorder. In general, early use of IV fluids containing adequate glucose (to prevent a catabolic state), parenteral or rectal antiemetics, and analgesics may abort the attack. Some patients respond to the triptans or ergotamine classes of medication.
  • Chronic prevention: Low-dose amitriptyline can be effective. Other antimigraine agents (eg, beta-blockers, anticonvulsants, calcium channel blockers) occasionally are useful. If serum carnitine is low, consider a trial of supplementation with l-carnitine. Some patients report improvement with mitochondrial cocktails of high-dose B vitamins and coenzyme Q10. There is no firm evidence for these measures.

Consultations

If an underlying metabolic disease, mitochondrial cytopathy, or inborn error of metabolism is suggested clinically, consult with a medical geneticist with expertise in metabolic disease.

Diet

• As for all migraineurs, diet, particularly certain chemicals in food, may precipitate attacks in some patients.
• Patients should keep a detailed diary of food, activities, and episodes in an attempt to identify precipitant(s).
• Rather than embarking on elimination diets, which are unlikely to be helpful, a trial of elimination may be useful if a particular food or additive is suspected as a trigger for the attacks.

Activity

• Some migraineurs experience attacks related to specific activities or exposures.
• The most common identifiable and avoidable precipitant is glare and/or flashing lights. Encourage children who are sensitive to glare to wear sunglasses when outdoors and to avoid strobes and strobelike conditions.

Medication

Acute treatment (symptomatic therapy) terminates the particular episode. Prophylactic treatment prevents episodes or reduces the number of attacks and/or severity of episodes. Medications used to treat or abort attacks include antiemetics, ergot alkaloids, serotonin agonists, and NSAIDs. Minor analgesics, with or without antiemetics or caffeine, are useful in most children. Avoid narcotics and sedatives in most patients. Some of the prophylactic medications that are effective in some patients with migraine variants include low-dose aspirin, beta-blockers, low-dose tricyclic antidepressants, cyproheptadine, calcium channel blockers, and low-dose anticonvulsants, including valproic acid or topiramate.

Antiemetics

May be used (oral, rectal, IV) if nausea and/or vomiting are prominent.

Promethazine HCl (Phenergan)

An antiemetic and sedative available in oral, rectal, and parenteral preparations; blocks postsynaptic mesolimbic dopaminergic receptors in the brain and reduces stimuli to the brainstem reticular system.

Dosing

Adult

Pediatric

<2 years: Contraindicated
>2 years: 0.25-1 mg/kg PO/PR; not to exceed 50 mg
Alternatively, 0.25-0.5 mg/kg IV/IM

Interactions

May have an additive effect when used concurrently with other CNS depressants or anticonvulsants; may cause hypotension when used concurrently with epinephrine

Contraindications

Documented hypersensitivity; children younger than 2 y (incidences of death due to respiratory depression)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Occasionally, patients experience paradoxic excitation; caution in patients with cardiovascular disease, impaired liver function, seizures, sleep apnea, and asthma

Metoclopramide (Reglan)

Blocks dopamine receptors in the chemoreceptor trigger zone of the CNS. Indicated for migraine-associated nausea.

Dosing

Adult

Pediatric

<6 years: 0.2-0.5 mg/kg/dose
>6 years: Start with 2.5 mg; for intractable vomiting, give IV starting with 0.1-0.2 mg/kg slow push; not to exceed 10 mg

Interactions

Anticholinergic agents may antagonize effects of metoclopramide; opiate analgesics may increase metoclopramide toxicity in CNS

Contraindications

Documented hypersensitivity; pheochromocytoma; GI hemorrhage, obstruction, or perforation; history of seizure disorders

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in history of mental illness and Parkinson disease; may precipitate dystonic reaction, which generally responds well to IV anticholinergic agent or diphenhydramine; less sedating than antiemetic doses of promethazine; if sedation and antiemetic action is needed, promethazine may be a better choice

Ergot alkaloids

Ergotamine preparations (alone or combined with caffeine) are direct vasoconstrictors of smooth muscle in cranial blood vessels. Their activity depends on the CNS vascular tone at administration. They also help establish the diagnosis. Ergot alkaloids should never be used to treat hemiplegic migraine.

Ergotamine (Cafatine, Cafergot, Cafetrate)

An alpha-adrenergic antagonist and serotonin antagonist that causes constriction of the peripheral and cranial blood vessels; effects are enhanced by caffeine.

Dosing

Adult

Pediatric

<12 years: Not established
>12 years: 1-2 mg PO/SL with or without 100-200 mg caffeine

Interactions

Increases effects of heparin and toxicity of nitroglycerin, propranolol, erythromycin, and clarithromycin

Contraindications

Documented hypersensitivity; hepatic or renal disease; sepsis; hemiplegic or ophthalmoplegic migraine; peripheral vascular disease

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Overdose may produce substantial peripheral vasoconstriction; overuse syndromes (frequent use for daily headaches) may cause habituation and severe rebound headaches; limit administration to 1-2 times per wk; avoid prolonged regimens because of danger of gangrene

Serotonin agonists

Sumatriptan or newer varieties stimulate 5-HT1 receptors, producing a direct vasoconstrictive effect. Serotonin agonists help establish the diagnosis, but they never should be used for hemiplegic migraine. Some triptans have slightly different pharmacokinetics or adverse effect profiles, but all have substantially the same mechanism as sumatriptan. None has been adequately evaluated in children.

Sumatriptan succinate (Imitrex)

First of the new-generation antimigraine agents that directly affect 5-HT1 receptors. Selective agonist for serotonin 5-HT1 receptors in cranial arteries; suppresses inflammation associated with migraine headaches. The nasal form has been demonstrated to have some efficacy in adolescents with migraine. Other forms have no proven efficacy in children, although uncontrolled reports suggest some efficacy.

Dosing

Adult

Pediatric

Use lowest effective dose
<12 years: Use cautiously in proportion to body weight
>12 years: 25-50 mg PO or 5 mg intranasally, suggested starting dose

Interactions

Toxicity increases when administered concomitantly with ergot-containing drugs, selective serotonin reuptake inhibitors, and MAOIs

Contraindications

Documented hypersensitivity; in hemiplegic migraine, basilar artery migraine, serious congenital heart disease, significant uncontrolled hypertension, and other significant neurologic focal symptoms that accompany attacks

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Avoid frequent use because of possible rebound headaches; dysesthesias are common, while significant chest pain is rare in young patients; hypertensive crisis, coronary artery vasospasm, cardiac arrest, peripheral ischemia, and bloody diarrhea may rarely occur when administering this medication

Dihydroergotamine (DHE-45, Migranal)

Alpha-adrenergic blocking agent with direct stimulating effect on smooth muscle of peripheral and cranial blood vessels; depresses central vasomotor centers. Mechanism of action is similar to ergotamine; nonselective 5-HT1 agonist with wide spectrum of receptor affinities outside 5-HT1 system; also binds to dopamine. Thus, has alpha-adrenergic antagonist and serotonin antagonist effect. Indicated to abort or prevent vascular headache when rapid control needed or when other routes of administration not feasible.
Usually administered in conjunction with antiemetics such as metoclopramide, which is a 5-HT3-receptor antagonist and a dopamine antagonist, to treat migraine-associated nausea.
Available in IV or intranasal preparations, tends to cause less arterial vasoconstriction than ergotamine tartrate. Not FDA approved for use in children.

Dosing

Adult

Pediatric

For refractory acute migraine, IV form can be titrated using adult protocol, combining titrating dose of DHE-45 with IV antiemetic to beneficial and tolerable dosing
Intranasal form is used as single dose, repeated no more than once in 30 min

Interactions

Increases effects of heparin and toxicity of nitroglycerin, propranolol, erythromycin, and clarithromycin; toxicity increases if administered concomitantly with other triptans, ergotamine, or other vasoconstrictors

Contraindications

Documented hypersensitivity; has used sumatriptan or zolmitriptan within previous 24 h; within 2 wk of discontinuing MAOIs

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Caution in angina, hypertension, impaired renal or hepatic function, or peripheral vascular disease; IV dosing typically causes nausea and should be preceded by IV dose of an appropriate antiemetic (eg, metoclopramide, promethazine, chlorpromazine); overuse can cause rebound headaches; excessive dose causes severe peripheral vasoconstriction with ischemia and may also cause agitation and hallucinations

Nonsteroidal anti-inflammatory agents (NSAIDs)

Most commonly used to relieve mild to moderate pain. Although effects of NSAIDs in treatment of pain tend to be patient specific, ibuprofen is usually DOC for initial therapy. In randomized trials, ibuprofen is one of the only agents with proven efficacy in pediatric migraine. Ibuprofen, sodium naproxen, or other NSAIDs, particularly if combined with or preceded by an antiemetic, may abort acute episodes.

Ibuprofen (Ibuprin, Advil, Motrin)

Inhibits pain, probably by decreasing activity of enzyme cyclooxygenase, which results in inhibition of prostaglandin synthesis.

Dosing

Adult

Pediatric

<12 years: 100-200 mg PO; starting dose for pain is 4-10 mg/kg q6h
>12 years: 400-600 mg PO as tab or syr

Interactions

Probenecid may increase concentrations and possibly toxicity of NSAIDs; may decrease effect of loop diuretics when administered concurrently; PT may increase when administered concurrently with anticoagulants; monitor PT and bleeding; may increase serum lithium levels and risk of methotrexate toxicity

Contraindications

Documented hypersensitivity to aspirin, iodides, or other NSAIDs; patients diagnosed with peptic ulcer disease, recent GI bleeding or perforation, renal insufficiency, and those at high risk of bleeding

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Not useful if vomiting is prominent feature, unless prior use of antiemetics makes PO administration tolerable; caution in patients with congestive heart failure, hypertension, and decreased renal and hepatic function

Beta-blockers

Effective in migraine prophylactic therapy, possibly by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing membranes, and/or increasing the release of oxygen to tissues.

Propranolol (Inderal)

Taken long-term, beta-blockers are frequently effective in reducing number of episodes and severity of attacks; when administering this medication, start with lowest dose and increase gradually (usually at monthly intervals) to allow maximum effect of each dose level.

Dosing

Adult

Pediatric

Starting dose: 10-20 mg PO bid; increase to as high as 60-80 mg bid if necessary

Interactions

Aluminum salts, barbiturates, calcium salts, cholestyramine, NSAIDs, penicillins, and rifampin may decrease bioavailability and plasma levels of propranolol, possibly resulting in decreased pharmacologic effect; conversely, haloperidol, hydralazine, loop diuretics, and MAOIs may increase metoprolol levels and its toxicity or pharmacologic effects

Contraindications

Documented hypersensitivity; asthma that requires beta agonists, insulin-dependent diabetes mellitus, and depressed mood

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

If patient experiences depressed mood, withdraw or try switching to atenolol; do not suddenly withdraw beta-blockers; for migraine treatment, full beta blockade is neither necessary nor desirable; assess pulse before and after a standard period of exercise prior to treatment and at follow-up visits; while resting and exercise pulse rates will both decrease, relative proportion of increase should be preserved; full beta blockade (ie, inability to raise pulse in response to exercise) is poorly tolerated and is not usually necessary; it is tolerated particularly poorly in athletes; beta-adrenergic blockade also may diminish signs and symptoms of acute hypoglycemia; beta-adrenergic blockers may reduce clinical signs (eg, tachycardia) of hyperthyroidism

Tricyclic antidepressants

Low-dose tricyclic antidepressants (eg, amitriptyline, imipramine, nortriptyline) are useful in preventing migraines, particularly in cyclic vomiting syndrome.

Amitriptyline (Elavil)

Administered at a low dose, may be particularly effective in cyclic vomiting of childhood.

Dosing

Adult

Pediatric

Start with lowest available dose
Young children: 5-10 mg PO qhs
Adolescents: 10-25 mg PO qhs; to avoid sedation, slowly titrate upwards
Maintenance dose: 20-50 PO mg/d PO; if ineffective and does not cause sedation, titrate to maximum 2-3 mg/kg/d PO divided bid or administer entire dose qhs

Interactions

Avoid use with diphenhydramine and other anticholinergics and antihistamines; use with other anticholinergic agents may be additive, resulting in significant sedation, dry mouth, and confusion; phenobarbital may increase metabolism, decreasing its effects, blocking uptake of guanethidine, and preventing hypotensive effects; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram

Contraindications

Documented hypersensitivity; in cardiac conduction disturbances, glaucoma, urinary retention history, and patients with seizures; do not administer to patients that have taken MAOIs in the past 14 d

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

If using higher doses of tricyclics, monitor ECG (for QTc) and blood levels for primary drug and metabolites; caution in patients with cardiac conduction disturbances, those with history of hyperthyroidism, and those with renal or hepatic impairment

Anticonvulsants

Valproic acid, topiramate, phenobarbital, and phenytoin usually have antimigraine activity in doses lower than those generally used for preventing seizures. Only divalproex sodium (Depakote) is approved specifically for migraine prophylaxis. Topiramate has been reported to reduce migraine attacks in adults but is not yet approved for migraine prophylaxis in children.

Divalproex sodium (Depakote)

A stable coordination compound, comprising sodium valproate and valproic acid in a 1:1 molar relationship; recently gained FDA approval for prevention of migraine; it is likely that all forms of valproic acid have similar efficacy; the following preparations can be used: 250 mg tablets, 125 mg sprinkle caps, or 250 mg/5 mL liquid (US preparations).

Dosing

Adult

Pediatric

Starting dose: 5-10 mg/kg PO divided bid; the dose can be increased gradually, not to exceed 30-40 mg/kg divided bid

Interactions

Substantial interactions occur with virtually all medications metabolized by p450 enzymes; primarily, these include other anticonvulsants, anticoagulants, and some antiretrovirals; because of potential thrombocytopenia and platelet antiaggregant effect, concurrent use of aspirin is a relative contraindication; small (but potentially significant) decrease in clearance and increase in half-life occur when taken concomitantly with cimetidine; erythromycin may increase serum concentrations, producing toxicity
Coadministration with felbamate may increase mean peak valproate levels by 35%; rifampin may increase oral clearance of valproate by 40%; in pediatric patients, protein binding and metabolism of valproate decrease when taken concomitantly with salicylates; when taken concurrently with valproate, variable changes in carbamazepine concentrations with increased levels of the active metabolite or decreased valproic acid levels with possible loss of seizure control may occur; displaces diazepam from its plasma albumin binding sites and inhibits its metabolism, increasing diazepam toxicity
Because it inhibits ethosuximide metabolism, monitor the serum levels of both drugs, especially in the presence of other anticonvulsants; inhibits phenobarbital metabolism, and phenobarbital can increase valproate clearance; increased action of phenytoin (even at therapeutic levels) or increased metabolism of valproic acid with decreased pharmacologic effects may occur; may displace warfarin from protein binding sites; monitor coagulation tests; zidovudine clearance may decrease in HIV-seropositive patients

Contraindications

Documented hypersensitivity; in hepatic disease or dysfunction or a history of thrombocytopenia from valproic acid

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Carefully monitor patients early in treatment; monitor periodically while patient is stable; adolescent girls may experience substantial weight gain and irregular menses; polycystic ovaries can develop; thrombocytopenic effect, particularly at higher doses and during intercurrent illnesses, may cause bruising and/or bleeding; mitochondrial syndromes may be worsened, thus, use with extreme caution; do not use in pregnant adolescents or sexually active adolescents who are not using adequate birth control

Topiramate (Topamax)

Migraine prophylaxis in adults is a labeled indication for use. Studies are underway in adolescents and children.
Is sedating and causes cognitive slowing if dose is advanced rapidly or starting dose is high.

Dosing

Adult

Pediatric

Start with smallest available dose and gradually increase until effective or dose-limiting side effects occur; young children typically start on 15-mg "sprinkle" capsules once or twice a day, advance by one capsule per week, switching to 25-mg "sprinkle" capsules once dose is beyond 45 mg bid; older children who can swallow tablets begin with 25-mg tab; increase by 25 mg/wk as needed and tolerated

Interactions

Phenytoin, carbamazepine, and valproic acid can significantly decrease topiramate levels; topiramate reduces digoxin and norethindrone levels, when administered concomitantly; concomitant use with carbonic-anhydrase inhibitors may increase risk of renal stone formation and should be avoided; use with extreme caution when administering concurrently with CNS depressants because may have an additive effect in CNS depression, as well as other cognitive or neuropsychiatric adverse events

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May promote renal stones formation, particularly in poor fluid intake; inform patients that adequate hydration is mandatory at all times; rare reports of oligohidrosis and heat stroke have occurred, as well as apparent induction of acute glaucoma; causes anorexia sufficient to provoke weight loss in up to 10% of children, particularly when medication is initiated; cognitive dulling and word finding problems are common when initiating, and slow titration is necessary to avoid cognitive adverse effects; sprinkle capsules should be swallowed whole or carefully open capsule and sprinkle contents on soft food immediately before ingestion, do not chew or crush

Calcium channel blockers

Migraine prophylaxis has been reported with various calcium channel blockers, including verapamil, nifedipine, and others. The calcium channel blocker with the highest evidence of efficacy is flunarizine, which is not available in the US. Results are not entirely predictable, and dosage must be individualized. Some patients experience exacerbation of migraine with these agents.

Verapamil (Calan, Calan SR, Covera-HS, Verelan)

Relaxes smooth muscles and increases oxygen delivery during vasospasms. Used in children for migraine with aura and basilar migraine. The drug has not been FDA-approved for use in migraine.

Dosing

Adult

Pediatric

2-4 mg/kg/d PO divided bid/tid; increase gradually as tolerated, not to exceed 8 mg/kg/d

Interactions

Alters metabolism of carbamazepine (increases serum levels); grapefruit juice and caffeine reduce clearance

Contraindications

Documented hypersensitivity; significant cardiac disease; hepatic or renal impairment

Precautions

Pregnancy

Precautions

May worsen headaches in some patients

Metabolic support

Metabolic support to prevent catabolic state is indicated in migrainelike episodes caused by suspected mitochondrial cytopathies. IV glucose and occasionally carnitine supplementation may be useful.

IV fluids containing either 5% or 10% dextrose

Goal is to prevent dehydration and catabolic state in mitochondrial cytopathies.

Dosing

Adult

Pediatric

Conventional volumes for fluid replacement and maintenance hydration, using fluids containing 5-10% dextrose

Interactions

None reported

Contraindications

Monitor blood sugar level; avoid hyperglycemia if using D10

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Monitor blood sugar level if using D10

Levocarnitine (Carnitor)

A vitaminlike substance that is necessary for transport of fatty acids into mitochondria; a cofactor in mitochondrial energy production. It can be deficient in organic acidurias and/or mitochondrial dysfunction and can be depleted with administration of valproic acid. Supplementation with L-carnitine may be helpful in mitochondrial cytopathies to prevent episodes of severe metabolic collapse and encephalopathy. Supplementation may be useful in cyclic vomiting or atypical migraine syndromes caused by mitochondrial dysfunction.

Dosing

Adult

Pediatric

25-100 mg/kg/d long-term PO dosing; in acute metabolic encephalopathies caused by mitochondrial dysfunction, higher IV dosage may be used briefly, not to exceed 300 mg/kg/d

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Check serum-free and total carnitine level before beginning treatment and to monitor dosing; excess PO carnitine causes diarrhea and GI distress; administration causes change in urine and body odor ("fishy smell")

Antihistamines

Cyproheptadine occasionally is useful for migraine prophylaxis, probably because of its serotonergic, rather than antihistaminic, effects. Other antihistamines generally are not useful for migraine prophylaxis.

Cyproheptadine (Periactin)

An antihistamine that has been used for migraine prevention in children more than in adults. Usually well tolerated. Mechanism of action not clarified, and hypotheses include antihistaminic and anti-5-HT 2 effects.

Dosing

Adult

Pediatric

2-4 mg PO tid; because of sedation, may need to start at lower dose

Interactions

Sedatives tend to be potentiated; concurrent use of MAOI contraindicated

Contraindications

Concurrent use of MAOI; unacceptable sedation or weight gain generally limits usefulness

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Cyproheptadine is an appetite stimulant; inform patient and parent of need to control dietary intake; also sedating, particularly when first started

Water soluble vitamins

Riboflavin, with or without magnesium supplements, with or without herbals (feverfew), has been used to prophylax migraine headaches. Dosage ranges from 200-400 mg/d for adults. No pediatric dose is established. The only side effect is bright yellow-green discoloration of urine. Patients should be warned about this harmless effect so they are not alarmed.

Riboflavin (Riobi)

Essential in the activation of pyridoxine and conversion of tryptophan to niacin. Component of flavoprotein enzymes, which are necessary for tissue respiration.

Dosing

Adult

400 mg PO qd

Pediatric

Not established

Interactions

Probenecid decreases absorption

Contraindications

None reported

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Riboflavin deficiency often occurs in presence of other B vitamin deficiencies

Electrolyte supplements

Magnesium salts, typically magnesium oxide, are combined in a commercial OTC preparation for migraine prophylaxis (MigreLief). Excess dosing may produce diarrhea.

Magnesium oxide (MagOx)

Used in migraine prophylaxis.

Dosing

Adult

300-400 mg PO qd

Pediatric

Not established

Interactions

May decrease effects of benzodiazepines, chloroquine, corticosteroids, digoxin, H2 antagonists, hydantoins, nitrofurantoin, tetracyclines, iron salts, ticlopidine, phenothiazines, iron salts; increases the effects of dicoumarol, quinidine, and sulfonylureas

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Hypermagnesemia and toxicity may occur in renal impairment when >50 mEq magnesium is given qd due to decreased clearance of magnesium ion; approximately 5-20% of orally administered magnesium salts can be systemically absorbed

Follow-up

Further Outpatient Care

Encourage patients and families to keep diaries of episodes, foods consumed, activities, illness, and medications. They should bring this list to follow-up visits to assist in identification of precipitants and to assess the efficacy of treatment.

Inpatient & Outpatient Medications

• Acute abortive treatment
  • Antiemetic and/or sedatives
  • Minor analgesics
  • Ergotamines
  • Triptans
  • Fluid replacement, if vomiting is severe
• Chronic prophylactic treatment is indicated if episodes are frequent, disruptive, and/or the patient and/or family desire treatment and are ready to comply with daily medication.
  • Beta-blockers
  • Tricyclic antidepressants
  • Aspirin (minidose)
  • Anticonvulsants
  • Cyproheptadine
  • High-dose vitamin B-2 (Riboflavin) combined with high doses of magnesium salts (usually magnesium oxide or citrate)

Complications

• Risk of stroke is higher in migraineurs, and patients with hemiplegic migraine may be at even higher risk.
• Abdominal migraine (cyclic vomiting syndrome) may cause significant dehydration.

Prognosis

Migraine variants may cause significant disability from loss of school time for the child, loss of work time for parents, and general disruption of family function.

Patient Education

• As with all migraine patients, education is an important part of care. Teach patients and families appropriate means to avoid and manage attacks.
• Instruct patient and parents to keep a detailed diary of episodes, food consumed, activities, and medications. The goal is to identify avoidable precipitants, assess attack patterns, and determine response to treatment.
• Making a specific diagnosis that episodes are migrainous in origin may be quite helpful. Often families are sufficiently relieved to know that the child does not have a more serious condition (eg, brain tumor) and that further medical intervention may not be necessary.
• For excellent patient education resources, see eMedicine's Headache Center. Also, visit eMedicine's patient education articles Causes and Treatments of Migraine and Related Headaches, Alternative and Complementary Approaches to Migraine and Cluster Headaches, Migraine Headache in Children, and Understanding Migraine and Cluster Headache Medications.

Miscellaneous

Medicolegal Pitfalls

The diagnosis of migraine and migraine variants is a clinical, based largely on a history of repeated episodes, with complete normalization between attacks. Imaging is useful only to rule out other causes, particularly in the acute setting, not to diagnose migraine or migraine variant. In an acute setting, particularly with a first attack, failure to find a serious alternative cause (eg, tumor, hemorrhage, hydrocephalus) would likely be viewed as a breach in standard of care.

• When the patient is symptomatic and has an abnormal neurological examination, migraine variant can almost never be diagnosed unless a consistent pattern exists of similar previous events and the child has had a well-documented normal examination between events. First episodes should never be diagnosed as variant migraine without carefully ruling out other serious pathology.
• Although alternative causes of symptoms are rare, most patients are not satisfied with a simple explanation and neuroimaging is often performed to rule out serious alternative pathology (eg, intracranial hemorrhage, tumor, hydrocephalus). If the physician decides that imaging is not indicated (eg, it has been repeatedly performed for similar attacks), the reasoning should be well documented in the medical record and a clear explanation should be given to the patient and family.

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Keywords

abdominal migraine, acute confusional migraine, basilar migraine, benign paroxysmal vertigo of childhood, cyclic vomiting of childhood, hemiplegic migraine, migraine, migraine aura without headache, ophthalmoplegic migraine, vascular headache, childhood migraine variants, migraine in children

Contributor Information and Disclosures

Author

Wendy G Mitchell, MD, Professor of Neurology, University of Southern California School of Medicine; Consulting Staff, Division of Child Neurology, Children's Hospital Los Angeles, Los Angeles County-University of Southern California
Wendy G Mitchell, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, Child Neurology Society, and International Child Neurology Association
Disclosure: Questcor Honoraria Consulting

Medical Editor

James J Riviello Jr, MD, George Peterkin Endowed Chair in Pediatrics, Professor of Pediatrics, Section of Neurology and Developmental Neuroscience, Professor of Neurology, Peter Kellaway Section of Neurophysiology, Baylor College of Medicine; Chief of Neurophysiology, Director of the Epilepsy and Neurophysiology Program, Texas Children's Hospital
James J Riviello Jr, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic
Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Neurology, Department of Neurology, Oregon Health and Science University; Consulting Staff, Shriners Hospital for Children
Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

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