Childhood Migraine Variants 

Updated: Nov 19, 2019
Author: Wendy G Mitchell, MD; Chief Editor: Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP 

Overview

Background

Presentations of migraine in children may be similar to adult presentations and may 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. In young children, migraine may present with prominent nonheadache symptoms (migraine without headache, or acephalalgic migraine), or neurologic symptoms (aura) may be much more prominent than the headache.

Previously called "childhood periodic syndromes that are commonly precursors of migraine" in International Headache Classification of Headache Disorders (ICHD)-II, these disorders were renamed "episodic syndromes that may be associated with migraine" in ICHD-3.[1]  Although historically noted to occur in childhood, they may also occur in adults.

Recognized childhood syndromes assumed to be pathophysiologically related to migraine include the following:

  • Benign paroxysmal vertigo of childhood

  • Abdominal migraine

  • Cyclic vomiting of childhood

  • Acute confusional migraine (acute confusional state)

  • Paroxysmal torticollis

  • Infant colic (epidemiologic association with migraine)

Basilar migraine (particularly in adolescent girls) may present with prominent dizziness and near-syncope 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.

Evidence suggests that infant colic may be an early-life expression of migraine. Epidemiologic associations are found between both infant colic and later migraine in the child, and maternal migraine.[2, 3]

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.

Pathophysiology and Etiology

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 play a contributing role. Migraine, in general, may have a genetic predisposition with environmental and systemic triggers. Hemiplegic migraine may be autosomal dominant. Common triggers reported by patients include stress, bright light, intense emotional influences, and too much or too little sleep.[4]

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.[5] There is increasing evidence that several mitochondrial DNA polymorphisms are associated both with cyclic vomiting syndrome and migraine without aura.[6] In subjects with mitochondrial disorders, fasting or systemic stress such as fever or illness may precipitate episodes.

As information from genetic diagnosis and whole exome sequencing rapidly expands, a number of channelopathy-related genetic syndromes have been found to include variable combinations of epilepsy syndrome, familial hemiplegic migraine, paroxysmal vertigo of childhood, episodic ataxia, and paroxysmal dyskinesias. For example, mutations in the SCN1a gene, originally associated with several epilepsy syndromes, are occasionally reported in familial hemiplegic migraine.[7] Similarly, mutations in PRRT2[8, 9] or the ATP1A2 gene[10] may present with variable phenotypes, including benign familial infantile seizures, paroxysmal choreoathetosis, episodic ataxia, and/or hemiplegic migraine.

Epidemiology

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.

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.

Epidemiological studies have linked infant colic with later migraine in children, suggesting that infant colic, a disorder in which there is apparently paroxysmal irritability and pain, may be a migraine variant as well.[3] In addition, maternal migraine history is epidemiologically associated with a higher incidence of infant colic, consistent with the assumption that tendency to migraine is inherited.[2]

Patient Education

For children with migraine variants, as for all migraine patients, education is an important part of care. Teach patients and families appropriate means of avoiding and managing attacks. Instruct the patient and the 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 the 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, a brain tumor) and that further medical intervention may not be necessary.

For patient education resources, see the Headache Center, as well as 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.

 

Presentation

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 or language disturbance, which clears in minutes to hours. Headache may be less dramatic than the hemiplegia. Other migrainous symptoms (eg, nausea, vomiting, and photophobia) are present to varying degrees. Hemiplegia may precede or accompany the headache.

Hemiplegic migraine is often familial, is dominantly inherited, and is linked to chromosome 19 in some studies.[11, 12] An alternative locus has been described on chromosome 1.[13, 14] 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).[15, 16] 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.

Additional genetic associations have been found including with mutations in SCN1a, ATP1A2, and PRRT2 genes. All of these mutations include variable phenotypes with epilepsy, paroxysmal dyskinesias, episodic ataxia, and hemiplegic migraine seen in affected families. Families with the same mutation may manifest differing combinations of symptoms, and the same symptoms may be due to different mutations.[7, 9, 10]

The diagnosis cannot be made during the first episode, though it may be suspected in the presence of a positive family history. Exclude more serious causes of headache with hemiplegia or hemiparesis, including intracranial hemorrhage, mass, infection, and 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.

The 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 (MELAS). On occasion, hemiplegic migraine may be associated with reversible unilateral cerebral edema on imaging.[17]

Confusional migraine

Although confusional migraine 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.

So-called "Alice-in-Wonderland syndrome" may be a special case of confusional migraine. The patient subjectively experiences the sensation of their own body being either larger or smaller than normal, and objects and people around them appearing larger or smaller, combining both somesthetic and visual perceptual disturbances. The same clinical syndrome can also be associated with a variety of viral illnesses, including influenza and EBV infection, but if it occurs repeatedly may be a migraine aura.[18]

Making the diagnosis during the first episode is difficult; it is possible only after the episode has resolved fully. Acute differential diagnosis of a single episode includes all types of encephalopathy or encephalitis, toxic ingestion, intoxication, and an unobserved seizure with postictal agitation.

Abdominal migraine

A child with abdominal migraine 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 or antimigraine therapies. The diagnosis is difficult to make during the first episode.

Cyclic vomiting of childhood, which can be associated with a mitochondrial cytopathy, may be a severe variant of abdominal migraine.

Basilar migraine

A patient with basilar migraine may have an aura followed by dizziness, vertigo, syncope, and dysarthria. Headache may be minimal or absent. This variant is observed most frequently in adolescent girls. The differential diagnosis includes cardiogenic or vasovagal syncope, inner ear disease, somatoform disorder, 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.

The 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 or tingling) similar to a more typical migraine aura may occur without subsequent head pain.

Benign paroxysmal vertigo of childhood

Given the high proportion of children with a family history of migraine, benign paroxysmal vertigo of childhood 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.

The syndrome presents with brief episodes of vertigo. Toddlers may be unable to verbalize the symptoms, but they typically cling to the parent and look frightened. Older children often verbalize that they are “moving.” Headache does not follow the attack.

Ophthalmoplegic migraine

Ophthalmoplegic migraine may begin in childhood. Acute disorders of eye movement, unilateral abnormal pupillary response, or Horner syndrome may precede or accompany the headache.

Physical Examination

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

Migraineurs have a higher risk of stroke, and patients with hemiplegic migraine may be at even higher risk. Abdominal migraine (cyclic vomiting syndrome) may cause significant dehydration.

 

DDx

Diagnostic Considerations

The diagnosis of migraine and migraine variants is a clinical one that is 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, or hydrocephalus) would likely be viewed as a breach in the standard of care.

When the patient is symptomatic and has an abnormal neurologic examination, migraine variant can almost never be diagnosed unless there is a consistent pattern 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 until other serious pathologic conditions have been carefully ruled out.

In addition to the conditions listed in the differential diagnosis (see below), other problems to be considered include the following:

  • Alternating hemiplegia of childhood

  • Benign occipital epilepsy of childhood

  • Cerebral autosomal dominant arteriopathy and subcortical infarcts and leukoencephalopathy (CADASIL),[19] for alternating hemiplegias presenting in adolescents

  • Complex partial status epilepticus

  • Ingestions

  • Intoxications

  • Organic acidurias

  • Somatoform disorder

Differential Diagnoses

 

Workup

Approach Considerations

During the first or worst episode, perform appropriate laboratory and neuroradiologic studies to exclude other causes of the symptoms.[20]

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, or hydrocephalus). If the physician decides that imaging is not indicated (eg, on the grounds that 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 the family.

For aura without headache, the differential diagnosis often includes simple partial (focal) seizures. Therefore, electroencephalography (EEG) or video EEG 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.

Laboratory Studies

Laboratory studies generally are not helpful between episodes when the patient has a history of multiple, recurrent episodes and complete clearing between episodes. 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

  • Serum ammonia

Samples must be collected carefully and handled appropriately by the laboratory. If suspicion of mitochondrial cytopathy is high, blood may be collected at any time to allow examination of the DNA for mitochondrial point mutations and deletions.

For families who appear to have clusters of symptoms including hemiplegic migraine, with or without epilepsy, paroxysmal dyskinesias and/or episodic ataxia, whole exome sequencing may be able to find the specific genetic cause. Additionally, the use of genetic panels that include sequencing of genes associated with specific symptoms (such as epilepsy or autism) have faster turn arounds, lower costs, and the yields can be similar to whole exomes.

CT, MRI, and SPECT

Neuroimaging with computed tomography (CT) or magnetic resonance imaging (MRI) is indicated during the first or worst attack that presents with simultaneous focal neurologic deficits or altered mental status; it should also be done 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 followed by complete recovery. In these patients, the clinician can usually rule out acute life-threatening conditions and can more reasonably make a diagnosis of migraine on the basis of the history.

During or immediately after an attack, functional neuroimaging may support the diagnosis, though migraine is most often a clinical diagnosis. Single-photon emission CT (SPECT) 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.

Electroencephalography

EEG may yield abnormal results during or immediately after an episode, showing a 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

Approach Considerations

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 (see Workup). When the child is first seen acutely, particularly during the first episode, more extensive evaluation may be necessary to exclude alternative diagnoses.

Treatment of childhood migraine variants has 2 aspects, as follows:

  • Short-term treatment of the specific attack

  • Long-term medication to reduce the 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 on weaker, often anecdotal, evidence.[21, 22]

If the clinical scenario suggests an underlying metabolic disease, mitochondrial cytopathy, or an inborn error of metabolism, consult a medical geneticist with expertise in metabolic disease.

Pharmacologic Therapy

Agents used for acute abortive treatment of childhood migraine variants include the following:

  • Antiemetic or sedatives

  • Minor analgesics

  • Ergotamines

  • Triptans[23, 24]

  • Fluid replacement solutions, if vomiting is severe

Long-term prophylaxis is indicated if episodes are frequent or disruptive and if patients or families desire treatment and are ready to comply with daily medication. Agents used for this purpose include the following:

  • Beta blockers

  • Tricyclic antidepressants (TCAs)

  • Aspirin (minidose)

  • Anticonvulsants

  • Cyproheptadine

  • High-dose vitamin B-2 (riboflavin) combined with high doses of magnesium salts (usually magnesium oxide or citrate)

Hemiplegic migraine

For acute treatment of hemiplegic migraine, antiemetics, mild sedatives, and nonnarcotic pain relievers are generally safe. However, vasoconstrictors, triptans, and ergotamine preparations are contraindicated.

For long-term prophylaxis, any of the agents used to prevent typical migraines may also be used to prevent hemiplegic migraines. Beta blockers, low-dose TCAs, low-dose daily aspirin (stopped during febrile illnesses), low-dose anticonvulsants, and calcium channel blockers can be administered. For a few patients with specific channelopathies, acetazolamide (Diamox) can be used to prevent attacks.

Flunarizine, a calcium channel blocker that is not available in the United States, 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 and with or without herbs (eg, feverfew).

Cyclic vomiting of childhood

If mitochondrial cytopathy or organic aciduria is suggested or diagnosed, acute treatment of cyclic vomiting of childhood should be tailored to the underlying disorder. In general, early use of intravenous (IV) fluids containing adequate glucose (to prevent a catabolic state), parenteral or rectal antiemetics, and analgesics may abort the attack. Some patients respond to triptans or ergotamines.

For long-term treatment of cyclic vomiting of childhood, low-dose amitriptyline (or another tricyclic antidepressant) can be effective. Other antimigraine agents (eg, beta blockers, anticonvulsants, and calcium channel blockers) are occasionally useful. If the serum carnitine level is low, consider a trial of supplementation with L-carnitine. Some patients report improvement with mitochondrial cocktails containing high-dose B vitamins and coenzyme Q10. There is no firm evidence for these measures.

Further outpatient care

Encourage patients and families to keep headache diaries.

Diet and Activity

In migraine variants, as in all types of migraine, diet (particularly certain chemicals in food), may precipitate attacks in some patients. Accordingly, patients should keep a detailed diary of episodes, foods consumed, activities, illness, and medications. They should bring this diary to follow-up visits to assist in identification of precipitants and to facilitate assessment of the efficacy of treatment.

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 of being a trigger for the attacks.

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

Medical Care

Referral to a child neurologist is indicated for children with migraines that fail to respond to abortive or first-line preventative medications. Additionally, a detailed eye exam including the optic nerve by ophthalmology is warranted, to ensure there is no evidence of elevated intracranial pressure that may warrant other treatments to preserve visual function.

 

Medication

Medication Summary

Acute treatment (symptomatic therapy) terminates the migraine variant episode. Prophylactic treatment prevents episodes or reduces their number or severity. Medications used to treat or abort attacks include antiemetics, ergot alkaloids, serotonin agonists, and nonsteroidal anti-inflammatory drugs (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 (TCAs), cyproheptadine, calcium channel blockers, and low-dose anticonvulsants, including valproic acid and topiramate. Acetazolamide (Diamox) is useful for selected patients with hemiplegic migraine due to specific channelopathies.

Antiemetic Agents

Class Summary

Antiemetics may be administered (orally, rectally, or intravenously [IV]) if nausea or vomiting is prominent.

Promethazine HCl (Phenergan, Phenadoz, Promethegan)

Promethazine is an antiemetic and sedative that is available in oral, rectal, and parenteral preparations. It blocks postsynaptic mesolimbic dopaminergic receptors in the brain and reduces stimuli to the brainstem reticular system.

Metoclopramide (Reglan, Metozolv)

Metoclopramide blocks dopamine receptors in the chemoreceptor trigger zone of the central nervous system (CNS). It is indicated for migraine-associated nausea.

Ergot Derivatives

Class Summary

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 (Ergomar)

Ergotamine is an alpha-adrenergic antagonist and serotonin antagonist that causes constriction of the peripheral and cranial blood vessels. Its effects are enhanced by caffeine. It is available as sublingual tab.

Dihydroergotamine (DHE-45, Migranal)

Dihydroergotamine is an alpha-adrenergic blocking agent that has a direct stimulating effect on the smooth muscle of peripheral and cranial blood vessels and depresses central vasomotor centers. Its mechanism of action is similar to that of ergotamine; it is a nonselective 5-HT1 agonist with a wide spectrum of receptor affinities outside the 5-HT1 system, and it also binds to dopamine. Thus, dihydroergotamine has alpha-adrenergic antagonist and serotonin antagonist effects.

Dihydroergotamine is indicated for aborting or preventing vascular headache when rapid control is needed or when other routes of administration are not feasible. It is not approved by the US Food and Drug Administration (FDA) for use in children.

Dihydroergotamine is usually administered in conjunction with antiemetics such as metoclopramide (a 5-HT3 receptor antagonist and a dopamine antagonist) to treat migraine-associated nausea. Dihydroergotamine is available in IV or intranasal preparations, and it tends to cause less arterial vasoconstriction than ergotamine tartrate does.

Antidepressants, SSRIs

Class Summary

Sumatriptan and other serotonin agonists stimulate serotonin 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, Alsuma, Sumavel DosePro)

Sumatriptan is the first of the antimigraine agents that directly affect 5-HT1 receptors. A selective agonist for serotonin 5-HT1 receptors in cranial arteries, it 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, though uncontrolled reports suggest some efficacy.

Nonsteroidal Anti-inflammatory Agents (NSAIDs)

Class Summary

NSAIDs are most commonly used to relieve mild to moderate pain. Although their efficacy in treating pain tends to be patient-specific, ibuprofen is usually the drug of choice for initial therapy. Ibuprofen, sodium naproxen, or other NSAIDs, particularly if combined with or preceded by an antiemetic, may abort acute episodes.

Ibuprofen (Ibuprin, Advil, Motrin)

Ibuprofen inhibits pain, probably by decreasing the activity of the enzyme cyclooxygenase, thereby inhibiting prostaglandin synthesis. In randomized trials, ibuprofen is one of the only agents with proven efficacy in pediatric migraine.

Indomethacin (Indocin)

Inhibition of prostaglandin synthesis reduces the delivery of solute to distal tubules, reducing urine volume and increasing urine osmolality. Indomethacin is usually used in nephrogenic diabetes insipidus.

Naproxen (Anaprox, Naprelan, Naprosyn)

Naproxen is well-absorbed orally and is not usually associated with rebound headaches. It is used for the relief of mild to moderate pain. Naproxen inhibits inflammatory reactions and pain by decreasing the activity of cyclo-oxygenase, which is responsible for prostaglandin synthesis. It is inexpensive and can be purchased over the counter.

Diclofenac (Voltaren, Cataflam XR, Zipsor, Cambia)

Diclofenac inhibits prostaglandin synthesis by decreasing cyclo-oxygenase activity, which, in turn, decreases the formation of prostaglandin precursors.

Ketoprofen

Ketoprofen is used for relief of mild to moderate pain and inflammation. Small dosages are indicated initially in small patients, elderly patients, and patients with renal or liver disease. Doses higher than 75 mg do not increase the therapeutic effects. Administer high doses with caution, and closely observe the patient's response.

Ketorolac (Sprix)

Ketorolac is indicated for short-term (up to 5 d) management of moderate to moderately severe pain. The bioavailability of a 31.5-mg intranasal dose (2 sprays) is approximately 60% of 30-mg IM dose. Intranasal spray delivers 15.75 mg per 100-µL spray; each 1.7-g bottle contains 8 sprays.

Beta-blockers

Class Summary

Beta-blockers are effective in migraine prophylactic therapy, possibly by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing membranes, or increasing the release of oxygen to tissues.

Propranolol (Inderal)

Taken long-term, beta-blockers such as propranolol are frequently effective in reducing the number and severity of attacks. When administering this medication, start with the lowest dose and increase the dose gradually (usually at monthly intervals) to allow each dose level to exert its maximum effect.

Timolol

Timolol is FDA approved for migraine prophylaxis, although there is less scientific evidence of efficacy for timolol than for propranolol.

Metoprolol (Lopressor, Toprol XL)

Metoprolol is not FDA approved for migraine prevention. Efficacy in prophylactic therapy is presumably by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing membranes, or increasing the release of oxygen to tissues.

Nadolol (Corgard)

Nadolol is not FDA approved for migraine prevention. Efficacy in prophylactic therapy is presumably by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing membranes, or increasing the release of oxygen to tissues.

Atenolol (Tenormin)

Atenolol is not FDA approved for migraine prevention. Efficacy in prophylactic therapy is presumably by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing membranes, or increasing the release of oxygen to tissues.

Tricyclic Antidepressants

Class Summary

In low doses, TCAs (eg, amitriptyline, imipramine, and nortriptyline) are useful in preventing migraines, particularly in patients with cyclic vomiting syndrome. These agents appear to exert their antimigraine effect independent of their effect on depression.

Amitriptyline

Amitriptyline has efficacy for migraine prophylaxis that is independent of its antidepressant effect. Its mechanism of action is unknown, but it inhibits activity of such diverse agents as histamine, 5-HT, and acetylcholine. When administered at a low dose, it may be particularly effective against cyclic vomiting of childhood.

Doxepin

Doxepin has efficacy for migraine prophylaxis that is independent of its antidepressant effect. Its mechanism of action is unknown, but it increases the concentration of serotonin and norepinephrine in the CNS by inhibiting their reuptake by the presynaptic neuronal membrane. It also inhibits histamine and acetylcholine activity.

Nortriptyline (Pamelor)

Nortriptyline has efficacy for migraine prophylaxis that is independent of its antidepressant effect. Its mechanism of action is unknown, but it inhibits activity of such diverse agents as histamine, 5-HT, and acetylcholine.

Protriptyline (Vivactil)

Protriptyline has efficacy for migraine prophylaxis that is independent of its antidepressant effect. It inhibits activity of such diverse agents as histamine, 5-HT, and acetylcholine.

Anticonvulsants

Class Summary

When given in doses lower than those generally used for preventing seizures, valproic acid, topiramate, phenobarbital, and phenytoin usually have antimigraine activity. Only divalproex sodium 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.

Valproic acid (Depakote)

Divalproex sodium is a stable coordination compound comprising sodium valproate and valproic acid in a 1:1 molar relationship; it is approved by the FDA for prevention of migraine. It is likely that all forms of valproic acid have similar efficacy. Preparations that can be used include 250-mg tablets, 125-mg sprinkle capsules, and 250 mg/5 mL liquid formulations (US preparations).

Gabapentin (Neurontin, Gralise)

Gabapentin is used for migraine headache prophylaxis. It has shown efficacy in migraine and transformed migraine.

Topiramate (Topamax)

Migraine prophylaxis in adults is a labeled indication for topiramate. Studies of this use of the drug in adolescents and children are under way. Topiramate is sedating and causes cognitive slowing if the dose is advanced rapidly or the starting dose is high.

Calcium Channel Blockers

Class Summary

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 United States. 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)

Verapamil relaxes smooth muscles and increases oxygen delivery during vasospasms. It is used in children for migraine with aura and basilar migraine. Verapamil has not been FDA-approved for use in migraine.

Metabolic Support

Class Summary

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.

Dextrose

Dextrose is administered with the goal of preventing dehydration and a catabolic state in mitochondrial cytopathies.

Levocarnitine (Carnitor)

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

Antihistamines

Class Summary

Cyproheptadine is occasionally useful for migraine prophylaxis, probably because of its serotonergic (as opposed to antihistaminic) effects. Other antihistamines generally are not useful for migraine prophylaxis.

Cyproheptadine (Periactin)

Cyproheptadine is an antihistamine that has been used for migraine prevention in children more than it has in adults. It is usually well tolerated. The mechanism by which cyproheptadine acts has not been clarified; hypotheses include antihistaminic and anti-5-HT2 effects.

Water-Soluble Vitamins

Class Summary

Riboflavin, with or without magnesium supplements and with or without herbs (eg, feverfew), has been used as prophylaxis for migraine headaches. For adults, the dosage ranges from 200-400 mg/day; no pediatric dose has been established. The only side effect is bright yellow-green discoloration of the urine. Patients should be warned about this harmless effect so that they do not become unduly alarmed.

Riboflavin (Riobi)

Riboflavin is essential in the activation of pyridoxine and the conversion of tryptophan to niacin. It is a component of flavoprotein enzymes, which are necessary for tissue respiration.

Electrolyte Supplements

Class Summary

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

Magnesium oxide (Mag-Ox)

Magnesium oxide is used in migraine prophylaxis.

 

Questions & Answers

Overview

What are childhood migraine variants (equivalents)?

What is the pathophysiology of childhood migraine variants (equivalents)?

What is the prevalence of childhood migraine variants (equivalents)?

What is included in patient education about childhood migraine variants (equivalents)?

Presentation

Which clinical history findings are characteristic of childhood migraine variants (equivalents)?

Which clinical history findings are characteristic of hemiplegic migraine in children?

Which clinical history findings are characteristic of confusional migraine in children?

Which clinical history findings are characteristic of abdominal migraine in children?

Which clinical history findings are characteristic of basilar migraine in children?

Which clinical history findings are characteristic of migraine aura without headache in children?

Which clinical history findings are characteristic of benign paroxysmal vertigo of childhood?

Which clinical history findings are characteristic of ophthalmoplegic migraine?

Which physical findings are characteristic of childhood migraine variants (equivalents)?

DDX

How are childhood migraine variants (equivalents) diagnosed?

Which conditions are included in the differential diagnoses of childhood migraine variants (equivalents)?

What are the differential diagnoses for Childhood Migraine Variants?

Workup

What is included in the workup of childhood migraine variants (equivalents)?

What is the role of lab tests in the workup of childhood migraine variants (equivalents)?

What is the role of neuroimaging in the workup of childhood migraine variants (equivalents)?

What is the role of EEG in the workup of childhood migraine variants (equivalents)?

Treatment

How are childhood migraine variants (equivalents) treated?

Which medications are used in the treatment of childhood migraine variants (equivalents)?

How is hemiplegic migraine treated in children?

How is cyclic vomiting of childhood treated?

What is included in the long-term monitoring of childhood migraine variants (equivalents)?

Which dietary modifications are used in the treatment of childhood migraine variants (equivalents)?

Which activity modifications are used in the treatment of childhood migraine variants (equivalents)?

Which specialist consultations are beneficial to patients with childhood migraine variants (equivalents)?

Medications

What is the role of medications in the treatment of childhood migraine variants (equivalents)?

Which medications in the drug class Electrolyte Supplements are used in the treatment of Childhood Migraine Variants?

Which medications in the drug class Water-Soluble Vitamins are used in the treatment of Childhood Migraine Variants?

Which medications in the drug class Antihistamines are used in the treatment of Childhood Migraine Variants?

Which medications in the drug class Metabolic Support are used in the treatment of Childhood Migraine Variants?

Which medications in the drug class Calcium Channel Blockers are used in the treatment of Childhood Migraine Variants?

Which medications in the drug class Anticonvulsants are used in the treatment of Childhood Migraine Variants?

Which medications in the drug class Tricyclic Antidepressants are used in the treatment of Childhood Migraine Variants?

Which medications in the drug class Beta-blockers are used in the treatment of Childhood Migraine Variants?

Which medications in the drug class Nonsteroidal Anti-inflammatory Agents (NSAIDs) are used in the treatment of Childhood Migraine Variants?

Which medications in the drug class Antidepressants, SSRIs are used in the treatment of Childhood Migraine Variants?

Which medications in the drug class Ergot Derivatives are used in the treatment of Childhood Migraine Variants?

Which medications in the drug class Antiemetic Agents are used in the treatment of Childhood Migraine Variants?