AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Background

Migraine is a paroxysmal headache disorder affecting more than 13% of the general population in the United States. Migraine is a syndrome and not a disease; it is characterized by paroxysmal headache associated with others signs and symptoms. About 80% of migraineurs have migraine without aura, while migraine with typical aura accounts for 15-20% of cases. Isolated migraine aura without headache (acephalic migraine) may be encountered in 5% of patients.

Migraine variant (MV) or migraine equivalent is the term applied to migraine, which exhibits itself in a form other than head pain. MV is characterized by paroxysmal episodes of prolonged visual auras; atypical sensory, motor, or visual aura; confusion; dysarthria; focal neurologic deficits; or gastrointestinal manifestations or other constitutional symptoms with or without a headache.

The diagnosis of MV is determined by history of paroxysmal signs and symptoms with or without cephalgia, a prior history of migraine with aura, in the absence of other medical disorders that may contribute to the symptoms. Many of these patients usually have a family history of migraine.

MVs are less recognized and poorly understood. They are less common than typical migraine without and with aura, and they usually affect children and young adults.

MVs should be differentiated from trigeminal cephalic neuralgias and other primary headaches such as stabbing and thunderclap headaches, cough headaches, or hypnic headaches. MVs should also be differentiated from exertional headaches, a group of headache syndromes associated with physical activity such as running, coughing, sneezing, or sexual intercourse.

Many MVs have been defined by the International Classification of Headache Disorders (ICHD-II) 2004 classification. These include hemiplegic migraines, basilar migraine, childhood periodic syndromes, retinal migraine, complicated migraines, and ophthalmoplegic migraine. Vertiginous migraine, acute confusional migraine of childhood, and nocturnal migraine, although well recognized entities, remain unclassified by the IHCD-II.

Pathophysiology

Although activation and sensitization of the trigeminovascular in migraine is believed to generate and maintain migraine pain, cortical spreading depression (CSD) is recognized as the phenomenon underlying migraine aura. CSD is believed to begin in the occipital region and to gradually spread rostrally. This phenomenon is accompanied by a transient oligemia, followed by hyperemia in other parts of the cortex. Various molecular and cellular mechanisms may lead to the increased susceptibility of CSD in migraineurs, which could potentially play an important role in the pathophysiology of MVs. Researchers have suggested that a vasogenic leakage from leptomeningeal vessels, with activation of the trigeminovascular system, probably contribute to the prolonged aura in patients with hemiplegic migraine.

Migraine with prolonged aura

The typical duration of a migraine aura, predominantly visual, is up to 30 minutes. In rare cases, the aura could be prolonged, lasting up to 60 minutes, raising concerns of possible stroke.

Migraine aura without headache or acephalic migraine

Around 3-5% of migraineurs experience an aura without headache. This presentation is more common in older patients who have had a history of migraine with aura during early age. Symptoms may include scintillating scotomata, formed stereotyped visual hallucinations in a single visual field or bilaterally, micropsia, and tunnel vision. Other auras include paroxysmal vertigo, hemisensory dysesthesias, and rarely auditory hallucinations. Acephalic migraine should be differentiated from transient ischemic attack, occipital lobe seizures, or temporal lobe seizures.

Hemiplegic migraine

Hemiplegic migraine is a very rare but well described form of MV. It was initially described in 1910 as a type of migraine consisting of recurrent headaches associated with temporary unilateral hemiparesis or hemiplegia, at times accompanied by ipsilateral numbness or tingling, with or without a speech disturbance. The focal neurologic deficit may precede or accompany the headache, which is usually less dramatic than motor deficit. Other migraine symptoms may variably be present. Patients may also experience disturbance of consciousness, and rarely coma. The neurologic deficit is transient and usually clears in minutes to hours, or resolves with the beginning of the headache phase.

Two forms of hemiplegic migraine are known: familial and sporadic. Both familial hemiplegic migraine (FHM) and sporadic hemiplegic migraine (SHM) are phenotypically similar subtypes of migraine with aura, differentiated only by the unilateral motor symptoms.

Familial hemiplegic migraine

FHM is an autosomal dominant disorder. FHM is a channelopathy; most of the affected families bear mutations in the CACNA1A gene (a defect linked to abnormal voltage-dependent P/Q-type calcium channel alpha-1A) on 19p13. Mutations in ATP1A2 (R548H) on 1q23 (Mendelian Inheritance in Man #182340) and other genes have been identified.

Alternating hemiplegic migraine (primarily in childhood)

Alternating hemiplegia of childhood (AHC) is a chronic progressive disorder, associated with high prevalence of neurologic deficit. It is distinguished from familial hemiplegic migraine by its infantile onset and by its characteristic associated symptoms. The onset of the disorder is before age 18 months. It is characterized by vomiting, headache, alternating hemiplegia, loss of consciousness, paroxysmal ocular palsies, choreoathetosis, autonomic dysfunction, and mental retardation. Single-photon emission computed tomography (SPECT) studies have shown progressive decrease of cerebral perfusion in cases of alternating hemiplegic migraine.

Sporadic hemiplegic migraine

SHM is defined as migraine attacks associated with motor weakness in the absence of family history of similar attacks. Cases of SHM have also been linked to the CACNA1A gene.

Diagnosis of FHM is usually confirmed with repeated stereotyped reversible episodes, particularly in the presence of positive family history of similar attacks. The absence of first- and or second-degree relatives with similar disorder raises suspicion of SHM. Differential diagnosis includes focal seizures with postictal paralysis, mitochondrial cytopathies, intracranial hemorrhage, mass, infection, or cerebral infarction.

Basilar-type migraine

Basilar migraine (BM), also known as Bickerstaff syndrome, consists of headache accompanied by dizziness, ataxia, tinnitus, decreased hearing, nausea and vomiting, dysarthria, diplopia, loss of balance, bilateral paresthesias or paresis, altered consciousness, syncope, and sometimes loss of consciousness. BM is observed most frequently in adolescent girls and young women. Localized vertebrobasilar vasoconstriction leading to transient posterior circulation ischemia may contribute to the symptomatology of the disorder. A novel mutation in the ATP1A2 gene, similar to FHM, has been reported in members of one family with BM. Differential diagnosis includes various causes of syncopal, inner ear disease, intoxication, and posterior fossa pathologies.

Childhood periodic syndromes that are commonly precursors of migraine

Childhood periodic syndromes are characterized by multiple cyclic attacks of pain or vomiting with our without migraine headaches. They are common in children and adolescents.

Cyclic vomiting syndrome

Cyclic vomiting of childhood is characterized by recurrent attacks of violent or prolonged vomiting without headache, which may last for hours. Attacks may be precipitated by infection, menstruation, or physical or emotional stress. During the attacks, patients characteristically show other symptoms of migraine such as nausea, lethargy, yawning, and drowsiness. Cyclic vomiting is thought to result from abnormal activity in the area postrema. Additionally, gastroparesis, which occurs during migraine, has been implicated as an etiologic factor for cyclic vomiting and abdominal migraine.

Abdominal migraine

Abdominal migraine most typically occurs in children, although it has been reported in adults. Patients usually complain of paroxysmal midabdominal pain lasting form 1-72 hours, associated with nausea and vomiting, flushing, or pallor. Like cyclic vomiting, attacks may be associated with other migraine prodromes such as fatigue and drowsiness. Aura and headaches are frequently absent or minimal. Patients may develop migraine late in their life, and family history of migraine is common. Gastroenterologic evaluation and workup is unremarkable.

Benign paroxysmal vertigo of childhood

Benign paroxysmal vertigo of childhood (BPVC) is another MV characterized by brief episodes of vertigo and disequilibrium lasting for hours, without headache, aura, hearing loss, or tinnitus. It affects children aged 1-4 years. Children usually complain of a spinning sensation during the attack. Typical migraine is common later in life, and a family history of migraine is helpful in confirming the diagnosis.

Retinal migraine

Retinal migraine (ophthalmic, ocular) is not an uncommon cause of transient monocular blindness in young adults. It is manifested by recurrent attacks of unilateral visual disturbance or blindness lasting from minutes to 1 hour, associated with minimal or no headache. This phenomenon is frightening to patients, who usually seek medical help to exclude amaurosis fugax due to ischemia of the retinal arteries. Patients describe a gradual visual disturbance in a mosaic pattern of scotomata that gradually enlarge, producing total unilateral visual loss. Postural changes, exercise, and oral contraceptive agents may precipitate attacks. The condition is thought to result from transient vasospasm of the choroidal or retinal arteries. A personal or family history of migraine confirms the diagnosis. The condition needs to be differentiated from ocular or vascular causes of transient monocular blindness, mainly carotid artery disease.

Complicated migraine

Complications of migraine include chronic migraine, status migrainosus, persistent aura without infarction, migrainous infarction, and migraine-triggered seizure. Complicated migraines are rare, accounting for less than 1% of total patients with migraine. Chronic migraine and status migrainosus are not considered MVs and therefore are not included in this article.

Persistent aura

A typical migraine aura usually lasts 20-60 minutes. When the aura of migraine is prolonged, lasting for hours or days, complicated migraine including ischemic strokes need to be excluded. Prolonged aura lasting beyond 60 minutes, in the absent of radiographic evidence of cerebral infarction, is referred to as migraine with persistent aura.

Migraine infarctions

The relationship between migraine, mostly migraine with aura, and ischemic stroke has been well recognized. Migraine, generally a benign condition, has been recognized as an independent risk factor for ischemic stroke. Additionally, migraine, predominantly migraine with aura, is associated with the presence of silent infarctions or white matter changes on brain MRI. When a cerebral infarction occurs during a typical migraine aura attack, the term migrainous infarction is used. The mechanism of migrainous infarction is complex. Whether the relationship between migraine and stroke is the consequence of other underlying etiologies or the presence of similar ischemic risk factors, or whether migraine is associated with conditions that could potentially cause stroke, is yet to be determined.

Migraine-triggered seizures (migralepsy)

Migraine and epilepsy are highly comorbid conditions probably sharing the same pathophysiology, but the nature of their association is unclear. Migralepsy is the term used when a seizure occurs during or within 1 hour of a typical migraine aura attack. Reversible brain MRI abnormalities have been reported in a patient with migraine-triggered seizure, possibly due to supratentorial focal cerebral edema. Electroencephalogram (EEG) findings are usually normal interictal, although various abnormalities, mainly diffuse slowing, have been reported in migraineurs.

Ophthalmoplegic migraine

This is a very rare condition in children, characterized by a migrainelike attack, followed within days by periorbital pain and diplopia secondary to cranial neuropathies. The oculomotor nerve is most commonly involved, with pupillary abnormality and ptosis, followed by the abducens, and rarely the trochlear nerve. The attack usually lasts from days to months and resolves spontaneously. A number of adult cases have been reported. Although previously considered an MV, the condition has been classified as neuralgia by the IHCD-II. The condition is thought to be due to recurrent demyelinating cranial neuropathies. Differential diagnosis includes conditions involving the parasellar, orbital, and posterior fossa leading to headache and ophthalmoplegia.

Acute confusional migraine (primarily in childhood)

Acute confusional migraine is a rare MV, almost exclusively seen in young children, manifested by episodes of confusion, disorientation, and vomiting, with or without headaches. The attacks are usually relieved by sleep. The condition should be differentiated from seizures, and various causes of confusion, including toxic, metabolic, mitochondrial, or infectious encephalopathies.

Vertiginous migraine

Growing evidence suggests that recurrent episodes of vertigo are related to migraine. Vertigo, a common complaint among migraineurs, has been reported in one third of cases. Recurrent episodes of vertigo lasting between 5 minutes and 1 hour, with or without nausea, vomiting, photophobia, or headache, in the setting of a previous personal history or a positive family history of migraine supports the diagnosis of vestibular or vertiginous migraine. The pathophysiology of migraine-related vertigo is not fully understood. Differential diagnosis includes vertebrobasilar insufficiency and paroxysmal vestibular syndromes.

Nocturnal migraine

Although not a true MV, nocturnal migraine is unique because of its occurrence during the middle of the night or early morning hours. Its nocturnal occurrence is thought to be related to circadian activation of certain neurotransmitters during sleep, which are known to trigger a migraine attack.

Frequency

United States

Migraine affects nearly 13% of the adult US population, with a postpubertal female-to-male ratio of 4:1. The frequency of the less common MVs varies with type and age. The prevalence of hemiplegic migraine is 0.03%; both familial and sporadic forms are equally frequent. The prevalence of the distinct alternating hemiplegic migraine of infancy is unknown. Similarly, the frequency of ophthalmoplegic, retinal, and confusional migraine is unknown.

Sex

Sex prevalence may be observed in some types of MVs. Basilar migraine and migraine aura without headaches are more common in women than in men. Similarly, hemiplegic migraine is more common in women, with a sex ratio (male-to-female) of 1:3.

• Basilar migraine in adults is more common in women than in men.
• Benign coital headache has a male-to-female ratio of 4:1.

Age

Specific MVs are observed at a higher incidence in different age groups. Ophthalmoplegic migraine, childhood periodic vomiting, and abdominal migraine are almost exclusively of childhood onset, affecting children younger than 10 years. In contrary, basilar and retinal migraines are more frequent in adolescents and young adults, while migraine aura without headache is mainly encountered in adults with long-standing history of migraine aura in early life. Hemiplegic migraine in its familial and sporadic forms has been reported in all age groups, while alternating hemiplegia of childhood is exclusive to children younger than 18 months.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

History

A detailed headache history is necessary to establish the diagnosis of MVs. As many as 20% of patients with MV may experience prodromal symptoms without subsequent headaches. Such paroxysmal symptoms, with the recurrent attacks of transient neurologic symptoms, whether a headache is absent or present, with a positive family history of migraine, and with a normal neurologic examination interictally are confirmatory.

• History of recurrent transient hemiplegia or hemiparesis that occurs during an attack of migraine headache suggests hemiplegic migraine. The hemiparesis may resolve prior to the headache or may persist for days to week.
• • Migraine aura without headaches is suspected in patients with history of recurrent attacks of unilateral transient monocular blindness in patients with otherwise absent risk factors for other causes of carotid disease and a personal or family history of migraine.
  • Patients with basilar migraine usually present with symptoms of vertebrobasilar insufficiency, which may precede a headache. The most common symptoms are dizziness and vertigo. Other symptoms, including visual disturbance (usually bilateral), dysarthria, acroparesthesias, tinnitus, confusion, or diplopia, may occur.
• Ophthalmoplegic migraine present with diplopia and periorbital pain with or without headache. Other symptoms include alteration of consciousness, acute confusion, recurrent vomiting, or seizures.
• Retinal migraine: A history of recurrent attacks of transient monocular visual disturbance or blindness with or without a headache, in the absence of other neurological symptoms is suggestive of retinal migraine.
• Cyclic vomiting should be suspected in children presenting with recurrent attacks of vomiting without headache, especially when a family history of migraine is present.
• A history of recurrent episodes of vertigo accompanied by other migrainous symptoms such as photophobia, headache, nausea, or vomiting is suggestive of vestibular migraine, predominantly in patients with a personal or family history of migraine.

Physical

The neurologic examination in between attack is nonfocal. Ictally, hemiparesis, ophthalmoplegia, or altered consciousness may be observed. Abnormalities of oculomotor nerve with pupillary involvement are seen in ophthalmoplegic migraine, followed by the abducens, and less commonly trochlear nerve palsy. Children with abdominal migraine or cyclic vomiting may show subtle clumsiness, attention deficit, or development delay. In migrainous infarction, some form of neurologic deficit with abnormal neuroimaging is present. Rarely, when patients with retinal migraine are evaluated and examined during an attack of visual loss, optic pallor or narrowing of the retinal vessels can be seen.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Other Problems to be Considered

Cerebral autosomal dominant arteriopathy and subcortical infarcts and leukoencephalopathy (CADASIL)
Episodic ataxia
Gastrointestinal motility disorders
Miller-Fisher syndrome
Volvulus

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Imaging Studies

• Patients with MV usually undergo unnecessary extensive and invasive diagnostic and laboratory evaluations before the diagnosis is made. A careful history of multiple attacks with complete recovery, with a symptom-free period in between attacks, and a family history of migraine or similar disorder is usually helpful in confirming the diagnosis.
• Neuroimaging (CT, MRI) is indicated when the patient presents with a first attack of focal neurologic deficits or altered mental status, or when focal findings persist between attacks. Neuroimaging studies are frequently obtained to exclude other acute causes of the symptoms and to exclude migrainous infarction in patients with persistent aura.
• • Imaging with MRI of the brain and MRA of the circle of Willis is indicated in ophthalmoplegic migraine to exclude posterior fossa or orbital pathologies associated with ophthalmoplegia. Abnormal enhancement on MRI and enlargement of the cisternal portion of the oculomotor nerve, have been reported. Further assessment may include a CT angiogram or lumbar puncture.
  • The yield for diagnostic testing in basilar migraine is low. Transient abnormalities on CT scan and MRI have been reported during or immediately following attacks. SPECT studies suggest decreased regional cerebral blood flow in the posterior circulation in basilar migraine during attacks, but transcranial Doppler studies have not revealed changes in blood flow velocities.
  • Invasive testing in children with periodic syndromes with a strong family history of migraine is unnecessary. A high-resolution MRI and magnetic resonance angiography (MRA) are indicated in suspicious cases in the absence of supportive family history.
• In retinal migraine, ruling out eye disease or vascular causes, especially when risk factors for arteriosclerosis exist, is important. Carotids Duplex sonography, transcranial Doppler study, MRA, or CT angiography examinations of the brain are helpful. Fluorescein or cerebral angiographies are rarely necessary. Hypercoagulability workup and sedimentation rate may be useful in excluding other coagulation disorders associated with retinal vasculopathy.

Other Tests

• EEG is unnecessary in MVs, except in conditions where seizure disorders need to be excluded, such as migraine-triggered seizure, and in patients with recurrent episodes of confusion. EEG generally does not offer additional information in migraineurs. In general, nonspecific interictal EEG abnormalities, including epileptiform activity, are reported in higher frequencies in migraineurs during or immediately after an episode, with slowing in focal or generalized patterns, and occipital spike-wave complexes.
• Continuous ambulatory or video EEG may be useful in patients with episodic confusion or recurrent focal neurologic deficits to exclude partial seizures or nonconvulsive status epilepticus.
• Genetic testing is now available for familial hemiplegic migraine using polymerase chain reaction to detect point mutations in the CACNA1A and ATP1A2 genes using and DNA sequencing is now available. Genetic testing may also be performed for other conditions associated with migraine such as CADASIL, an autosomal dominant disorder in which patients may present with migraine, multiple subcortical strokes, and dementia in early adulthood.
• In children with cyclic vomiting, a serum lactate level is helpful in excluding mitochondrial disorders. Other tests including, upper and lower gastrointestinal series and vagal autonomic function testing, are rarely indicated.
• More recently, functional neuroimaging studies during and immediately after an attack of migraine have demonstrated abnormalities of perfusion and have helped in understanding the pathophysiology of auras. Similarly, SPECT might show hypoperfusion during the aura phase.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Medical Care

The first step in treatment is to establish the diagnosis. Once the syndromes are recognized, MVs respond to typical migraine preventive medications.

Treatment is divided into eliminating particular triggers, acute management of the specific attack, and long-term preventive approach. Patients should follow risk factor modifications including smoking cessation, and they should avoid the use of hormonal replacement therapy and birth control pills, all of which could potentially increase the risk of hypercoagulability migraineurs.

• In hemiplegic migraine, acute treatment options include antiemetics, nonsteroidal anti-inflammatory drugs, and nonnarcotic pain relievers. Triptans and ergotamine preparations are contraindicated because of their potential vasoconstrictive effects. Prophylactic treatment is generally warranted because of the severity of the attacks. No data are available to support the use of any particular antimigraine agent. Beta-blockers, low-dose tricyclics, anticonvulsants, and calcium channel blockers can be administered. Acetazolamide has been frequently prescribed to patients with hemiplegic migraine, but its benefit in decreasing the frequency or severity of the attacks is questionable. No data support the use of antiplatelet therapy to decrease the risk of stroke.
• In ophthalmoplegic migraine, prednisone has been used with mixed results. The data on the benefit of prophylactic therapy with beta-blockers, such as propranolol, are anecdotal.

  In retinal migraine, vasoconstrictive agents such as triptans and ergots should be avoided. The use of prophylactic therapy is also anecdotal; when considered, calcium channel blockers are preferred.

• In migraine-triggered seizures, antiepileptic agents are drugs of choice because of their dual benefit in migraine prevention and seizure control
• In childhood periodic vomiting syndrome, early use of intravenous fluids containing adequate glucose (to prevent a catabolic state) and analgesics may abort the attack. Some patients respond to the triptans or ergotamine classes of medication. Antiemetic drugs are usually not effective, but ondansetron may be more efficacious given its central mechanism of action. Preventive medications such as cyproheptadine and tricyclic antidepressants are preferred in children.
• Abdominal migraine symptoms are usually relieved with sleep. Antiemetics may help aborting an acute attack. For chronic prevention, low doses of tricyclic antidepressants and flunarizine, a calcium channel blocker, are effective. Other migraine prevention medications are occasionally of some benefit.
• Triptans, ergots, and dihydroergotamine are contraindicated in patients with migrainous infarction. These patients may respond to nonsteroidal anti-inflammatory drugs (NSAIDs), antiemetics, and non-narcotic pain relievers. Prophylactic therapy is recommended, with tricyclics, beta-blockers, calcium channel blockers, or antiepileptic drugs. Long-term antiplatelet therapy is indicated in patients with migrainous infarction.
• Patients with vertiginous migraine rarely respond to migraine prophylactic therapy. Anecdotal data are available on the benefit of verapamil, a calcium channel blocker, and amitriptyline, a tricyclic antidepressant, because of their anticholinergic properties, which may help control the vertigo.

Consultations

Consultation with a neuro-ophthalmologist is warranted in patients who present with persistent visual aura, retinal migraine, or recurrent ophthalmoplegia. Children with cyclic vomiting syndrome rarely require an evaluation by a gastroenterologist to exclude other gastrointestinal disorders. An evaluation by an audiologist may be necessary to exclude other vestibulopathies in patients with vertiginous migraine.

MEDICATION

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Carbonic anhydrase inhibitors (diuretic)

Carbonic anhydrase (CA) is an enzyme found in many tissues. It catalyzes a reversible reaction whereby carbon dioxide becomes hydrated and carbonic acid dehydrated. These changes may result in a decrease in cerebrospinal fluid by the choroid plexus.

Drug Category: Antiemetics

These agents typically are used in migraine and MVs, especially when nausea and vomiting are prominent.

Drug Name	Promethazine (Phenergan)
Description	Used to control symptoms of nausea and vomiting.
Adult Dose	12.5-25 mg PO/IV/IM/PR q6h
Pediatric Dose	<2 years: Contraindicated >2 years: 12.5-25 mg PO/PR q6h prn
Contraindications	Documented hypersensitivity; asthma; children younger than 2 y (incidences of death due to respiratory depression)
Interactions	May have additive effects when used concurrently with other CNS depressants or anticonvulsants; coadministration with epinephrine may cause hypotension
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	Caution in cardiovascular disease, impaired liver function, seizures, sleep apnea, asthma, bone marrow depression, compromised respiratory function, stenosing peptic ulcer, seizure disorders, pediatric patients > 2 y

Drug Category: Calcium channel blockers

These agents inhibit calcium ions from entering slow channels, select voltage-sensitive areas, or vascular smooth muscle.

Drug Name	Flunarizine
Description	Not available in the US.
Adult Dose	10 mg PO qhs
Pediatric Dose	Not established; suggested dosing includes <40 kg: 5 mg PO qd >40 kg: 10 mg PO qd
Contraindications	Documented hypersensitivity; depression; extrapyramidal symptoms
Interactions	Avoid with beta-blockers
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 cause drowsiness

Drug Category: Antihistamines

These agents prevent histamine response in sensory nerve endings and blood vessels. They are more effective in preventing histamine response than in reversing it.

Drug Category: Tricyclic antidepressants

These agents are used for migraine prophylaxis that is effective independent of antidepressant effect. Mechanism of action is unknown. These agents inhibit activity of such diverse agents as histamine, 5-HT, and acetylcholine.

Drug Category: Anticonvulsants

Anticonvulsants, particularly those that interact with the GABAergic system, seem to have a positive effect in reducing migraine attacks. Valproate and gabapentin are most commonly used in this manner.

Drug Name	Valproic acid (Depakote, Depakene)
Description	Delayed-release or extended-release dosage forms are used for prophylaxis of migraine headaches. Although mechanism of action is not established, activity may be related to increased brain levels of GABA, or enhanced GABA action.
Adult Dose	Delayed-release: 250 mg PO bid initially; may titrate upward, not to exceed 1000 mg/d divided bid Extended-release: 500 mg PO qd initially; may increase dose, not to exceed 1000 mg/d
Pediatric Dose	<10 years: Not established >10 years: 250 mg PO bid; 1000 mg/d maximum
Contraindications	Documented hypersensitivity; hepatic disease/dysfunction; hyperammonemic encephalopathy and urea cycle disorders
Interactions	Coadministration with cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may significantly reduce valproate levels; in pediatric patients, protein binding and metabolism of valproate decrease when taken concomitantly with salicylates; coadministration with carbamazepine may result in variable changes of carbamazepine concentrations with possible loss of seizure control; valproate may increase diazepam and ethosuximide toxicity (monitor closely); valproate may increase phenobarbital and phenytoin levels while either one may decrease valproate levels; valproate may displace warfarin from protein-binding sites (monitor coagulation tests); may increase zidovudine levels in HIV-seropositive patients
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Thrombocytopenia and abnormal coagulation parameters have occurred; risk of thrombocytopenia increases significantly at total trough valproate plasma concentrations >110 mcg/mL in females and >135 mcg/mL in males; at periodic intervals and prior to surgery, determine platelet counts and bleeding time before initiating therapy; reduce dose or discontinue therapy if hemorrhage, bruising, or a hemostasis/coagulation disorder occur; hyperammonemia may occur, resulting in hepatotoxicity; monitor patients closely for appearance of malaise, weakness, facial edema, anorexia, jaundice, and vomiting; may cause drowsiness

FOLLOW-UP

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

In/Out Patient Meds

• Acetazolamide
• Ondansetron

Patient Education

Benign coital headache: If coital headaches have been a problem for a significant period of time, the patient or couple may need psychological counseling.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

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• De Romanis F, Buzzi MG, Assenza S. Basilar migraine with electroencephalographic findings of occipital spike-wave complexes: a long-term study in seven children. Cephalalgia. Jun 1993;13(3):192-6; discussion 150. [Medline].
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Article Last Updated: Sep 12, 2006