Migraine is a disorder affecting more than 13% of the general population in the United States. (See also Migraine in Children.) It is not a disease but a syndrome that is characterized by paroxysmal headache associated with other signs and symptoms. About 80% of migraineurs have migraine without aura, whereas migraine with typical aura accounts for 15-20% of cases. Isolated migraine aura without headache (acephalalgic migraine) may be encountered in 5% of patients. 
Migraine variant (or migraine equivalent) is the term applied to a migraine that exhibits itself in a form other than head pain. Such conditions are less recognized, less common, and less well understood than the typical migraines (both without and with aura) that usually affect children and young adults. Migraine variants may be characterized by the following:
Paroxysmal episodes of prolonged visual auras
Atypical sensory, motor, or visual aura
Focal neurologic deficits
Gastrointestinal (GI) manifestations
Other constitutional symptoms, with or without a headache
The diagnosis of migraine variant is determined by a history of paroxysmal signs and symptoms with or without cephalalgia and a previous 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.
Migraine variants should be differentiated from trigeminal autonomic cephalalgias, which include cluster headaches, paroxysmal hemicrania, and syndrome of neuralgiform conjunctival injection and tearing. These syndromes should also be differentiated from other primary headache disorders, such as stabbing headache, thunderclap headaches, hypnic headaches and hemicrania continua, and primary headache syndromes associated with physical activity (eg, exertional headaches, cough headaches, and headaches associated with sexual activity).
Many migraine variants have been defined by the International Classification of Headache Disorders 2004 classification (ICHD-II), including the following: 
Childhood periodic syndromes - renamed "episodic syndromes that may be associated with migraine" in ICHD-III beta 
Less common forms of migraine, such as acute confusional migraine of childhood, vertiginous migraine, and nocturnal migraine, remain unclassified by the ICHD-II.
Chronic migraine and status migrainosus are not considered migraine variants and therefore are not included in this article.
Migraine is associated with a neuronal network excitability, with activation and sensitization of the trigeminovascular system. Cortical spreading depression (CSD), recognized as the neuronal phenomenon underlying visual aura, is believed to begin in the occipital region and then gradually spread anteriorly.  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 to CSD in migraineurs, which could potentially play an important role in the pathophysiology of migraine variants. 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 affects nearly 13% of the adult US population, with a postpubertal female-to-male ratio of 4:1. The frequency of the less common migraine variants varies with the migraine type and patient 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 prevalences of ophthalmoplegic, retinal, and confusional migraine are unknown.
Sex-related differences in prevalence may be observed in some types of migraine variants. 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 male-to-female sex ratio of 1:3. Benign coital headache has a male-to-female ratio of 4:1.
Specific migraine variants are observed at different frequencies in different age groups,  as follows:
Ophthalmoplegic migraine, childhood periodic vomiting, and abdominal migraine are almost exclusively of childhood onset, affecting children younger than 10 years
Basilar and retinal migraines are more frequent in adolescents and young adults
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
Alternating hemiplegia of childhood is exclusive to children younger than 18 months
Hemiplegic migraine is a very rare but well-described form of migraine variant. 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.
Thus, a history of recurrent transient hemiplegia or hemiparesis that occurs during an attack of migraine headache suggests hemiplegic migraine. The hemiparesis may resolve before the headache or may persist for days to weeks.
The focal neurologic deficit may precede or accompany the headache, which is usually less dramatic than the motor deficit. Other migraine symptoms may be present to varying degrees. Patients may also experience disturbance of consciousness, and, rarely, coma. [8, 9, 10, 11, 12, 13] The neurologic deficit is transient and usually clears in minutes to hours, or it may resolve with the beginning of the headache phase. [14, 15, 16, 17, 18]
Two forms of hemiplegic migraine are known: familial hemiplegic migraine (FHM) and sporadic hemiplegic migraine (SHM). The 2 forms are phenotypically similar subtypes of migraine with aura, differentiated only by the unilateral motor symptoms. [19, 20]
Familial hemiplegic migraine
FHM is a genetically heterogeneous autosomal dominant disorder and a channelopathy; most of the affected families (FHM1) bear mutations in the CACNA1A gene (a defect linked to abnormal voltage-dependent P/Q-type calcium channel alpha-1A) on 19p13. [21, 22, 23, 24, 25, 26] In FHM type 2 (FHM2), mutation in ATP1A2 (R548H) on 1q23 was identified, encoding the alpha2-subunit of sodium/potassium pumps. [27, 28, 29, 30] A third novel mutation in sodium channel gene SCN1A has also been identified in FHM3. 
Genetic testing is available for FHM by using polymerase chain reaction (PCR) testing to detect point mutations in the CACNA1A and ATP1A2. DNA sequencing is also available. Positron emission tomography (PET) studies have shown glucose hypometabolism in the contralateral perisylvian region early during a hemiplegic migraine. 
Alternating hemiplegic migraine
Alternating hemiplegia primarily occurs in childhood (hence the name alternating hemiplegia of childhood [AHC]) and is a chronic progressive disorder, associated with a high prevalence of neurologic deficit.  This condition is distinguished from FHM by its infantile onset and by its characteristic associated symptoms. 
The onset of the disorder is before age 18 months,  and it is characterized by vomiting, headache, alternating hemiplegia, loss of consciousness, paroxysmal ocular palsies, choreoathetosis, autonomic dysfunction, and mental retardation. [36, 37] Single-photon emission computed tomography (SPECT) studies have shown progressive decrease of cerebral perfusion in cases of alternating hemiplegic migraine.
Sporadic hemiplegic migraine
The diagnosis of FHM is usually confirmed with repeated stereotyped reversible episodes, particularly in the presence of a positive family history of similar attacks. However, the absence of first- and or second-degree relatives with similar disorder raises suspicion of SHM.  The differential diagnosis for SHM includes focal seizures with postictal paralysis, mitochondrial cytopathies, intracranial hemorrhage, mass, infection, and cerebral infarction. 
In hemiplegic migraine, acute treatment options include antiemetics, nonsteroidal anti-inflammatory drugs (NSAIDs), and nonnarcotic pain relievers. 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, but beta blockers, low-dose tricyclic antidepressants, 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.
Patients with basilar migraine (also known as Bickerstaff syndrome) usually present with symptoms of vertebrobasilar insufficiency, which may precede a headache. The most common symptoms are dizziness and vertigo, but symptoms may also include headache accompanied by ataxia, tinnitus, decreased hearing, nausea and vomiting, dysarthria, diplopia, loss of balance, bilateral paresthesias or paresis, altered consciousness, syncope, and, sometimes loss of consciousness. 
Basilar migraine is observed most frequently in adolescent girls and young women.  Localized vertebrobasilar vasoconstriction leading to transient posterior circulation ischemia may contribute to the symptoms of the disorder.  A novel mutation in the ATP1A2 gene, similar to that seen in familial hemiplegic migraine (FHM), has been reported in members of a family with basilar migraine.
The differential diagnosis includes various causes of syncopal, inner-ear, intoxication, and posterior-fossa pathologies.  However, the yield for diagnostic testing is low. Transient abnormalities on computed tomography (CT) and magnetic resonance imaging (MRI) have been reported during or immediately after attacks. Single-photon emission CT (SPECT) studies suggest decreased regional cerebral blood flow in the posterior circulation during attacks, but transcranial Doppler ultrasonography has not revealed changes in blood flow velocities.
Childhood Periodic Syndromes
Childhood periodic syndromes (renamed "episodic syndromes that may be associated with migraine" in ICHD-III beta  ) are characterized by multiple cyclic attacks of pain or vomiting, with our without migraine headaches. These syndromes are common in children and adolescents and are commonly precursors of migraine. Invasive testing in children with periodic syndromes who have a strong family history of migraine is unnecessary. High-resolution magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) are indicated in suspicious cases in the absence of a supportive family history.
Cyclic vomiting syndrome
Cyclic vomiting of childhood is characterized by recurrent attacks of violent or prolonged vomiting without headache, which may last for hours. [48, 49, 50] Cyclic vomiting syndrome should especially be suspected in this setting when there is an associated family history of migraine.
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. Children with cyclic vomiting may show subtle clumsiness, attention deficit, or development delay.
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. [51, 52, 53]
A serum lactate level is helpful in these children to exclude mitochondrial disorders. Other tests are rarely indicated, including upper and lower gastrointestinal (GI) series and vagal autonomic function testing.
Early use of intravenous (IV) 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 as a result of its central mechanism of action. Preventive medications, such as cyproheptadine and tricyclic antidepressants (TCAs), are preferred in children.
Abdominal migraine most typically occurs in children, though it has been reported in adults.  Patients usually complain of paroxysmal midabdominal pain lasting from 1 to 72 hours, associated with nausea and vomiting, flushing, or pallor. As in cyclic vomiting, attacks may be associated with other migraine prodromes, such as fatigue and drowsiness. Aura and headaches are frequently absent or minimal. Children with abdominal migraine may show subtle clumsiness, attention deficit, or development delay.
Patients may develop migraine late in life, and a family history of migraine is common. Gastroenterologic evaluation and workup typically yield unremarkable results. 
Abdominal migraine symptoms are usually relieved with sleep. Antiemetics may help in aborting an acute attack. For long-term prevention, low doses of TCAs and flunarizine, a calcium channel blocker, are effective.  Other migraine-preventing medications are occasionally of some benefit.
Benign paroxysmal vertigo of childhood
Benign paroxysmal vertigo of childhood (BPVC) is characterized by brief episodes of vertigo and disequilibrium lasting for hours, without headache, aura, hearing loss, or tinnitus. This disorder affects children aged 1-4 years, who 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 of BPVC.
Retinal migraine (also called ophthalmic or ocular migraine) is a fairly common cause of transient monocular blindness in young adults. [56, 57] This disorder 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. [58, 59, 60]
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. 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.
Retinal migraine is thought to result from transient vasospasm of the choroidal or retinal arteries. A history of recurrent attacks of transient monocular visual disturbance or blindness, with or without a headache and without other neurologic symptoms, is suggestive of retinal migraine. A personal or family history of migraine confirms the diagnosis.
Ruling out eye disease or vascular causes, especially when risk factors for arteriosclerosis exist, is important. That is, the condition must be differentiated from ocular or vascular causes of transient monocular blindness, mainly carotid artery disease. [61, 62]
Carotid Duplex ultrasonography, transcranial Doppler ultrasonography, magnetic resonance angiography (MRA), or computed tomography angiography (CTA) of the brain may be helpful. Fluorescein or cerebral angiography is rarely necessary. A hypercoagulability workup and evaluation of the erythrocyte sedimentation rate may be useful in excluding other coagulation disorders associated with retinal vasculopathy.
Ophthalmoplegic migraine is a very rare condition that occurs predominantly in children and is characterized by a migrainelike attack that is followed within days by periorbital pain and diplopia secondary to cranial neuropathies. [57, 63] Headache may or may not be present.
The oculomotor nerve is most commonly involved, with pupillary abnormality and ptosis, followed by the abducens nerve and, rarely, the trochlear nerve. Other symptoms include alteration of consciousness, acute confusion, recurrent vomiting, and seizures. The attack usually lasts from days to months and resolves spontaneously. [64, 65, 66] A number of adult cases have been reported.
Although ophthalmoplegic migraine was previously considered a migraine variant, it is categorized as a neuralgia in the 2004 version of the International Classification of Headache Disorders (ICHD-II). The condition is thought to be due to recurrent demyelinating cranial neuropathies.
The differential diagnosis includes conditions involving the parasellar, orbital, and posterior fossa.  Magnetic resonance imaging (MRI) of the brain and magnetic resonance angiography (MRA) of the circle of Willis are indicated 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 computed tomography angiography (CTA) or lumbar puncture.
Complications of migraine include chronic migraine, status migrainosus, persistent aura without infarction, migrainous infarction, and migraine-triggered seizure.  These disorders are rare, accounting for fewer than 1% of total patients with migraine. Neuroimaging studies are frequently obtained to exclude other acute causes of the symptoms and to exclude migrainous infarction in patients with 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 absence of radiographic evidence of cerebral infarction, is referred to as migraine with persistent aura.
The relationship between migraine, mostly migraine with aura, and ischemic stroke has been well recognized. In fact, 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 magnetic resonance imaging (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. It remains to be determined whether the relation between migraine and stroke is the consequence of other underlying conditions or the presence of similar ischemic risk factors or whether migraine is associated with conditions that could potentially cause stroke. [70, 71]
Triptans, ergots, and dihydroergotamine are contraindicated in patients with migrainous infarction. These patients may respond to nonsteroidal anti-inflammatory drugs (NSAIDs), antiemetics, and nonnarcotic pain relievers. Prophylaxis with tricyclic antidepressants, beta blockers, calcium channel blockers, or antiepileptic drugs is recommended. Long-term antiplatelet therapy is indicated in patients with migrainous infarction.
Migraine and epilepsy are highly comorbid conditions, probably sharing the same pathophysiology, but the nature of their association is unclear. Migralepsy (migraine-triggered seizures) 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 as a consequence of supratentorial focal cerebral edema. [73, 74] Normal interictal findings are usually noted on electroencephalography (EEG), though various abnormalities, mainly diffuse slowing, have been reported in migraineurs.
Antiepileptic agents are the drugs of choice because of their dual benefit in migraine prevention and seizure control.
Less Common Migraine Variants
Acute confusional migraine
Acute confusional migraine is a rare migraine variant that is almost exclusively seen in young children. It is manifested by episodes of confusion, disorientation, and vomiting, with or without headaches. [75, 76, 77] The attacks are usually relieved by sleep. This condition should be differentiated from seizures and from various causes of confusion, including toxic, metabolic, mitochondrial, or infectious encephalopathies.
Growing evidence suggests that recurrent episodes of vertigo are related to migraine. [48, 78] 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 vertiginous (vestibular) migraine. The pathophysiology of migraine-related vertigo is not fully understood. 
The differential diagnosis includes vertebrobasilar insufficiency and paroxysmal vestibular syndromes.
Patients with vertiginous migraine rarely respond to migraine prophylaxis. Anecdotal data are available on the benefits of the calcium channel blocker verapamil, and the tricyclic antidepressant amitriptyline; their anticholinergic properties may help control the vertigo.
Although nocturnal migraine is not a true migraine variant, it is unique in that it occurs during the middle of the night or the 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.
Migraine variant is characterized by paroxysmal episodes of prolonged visual auras; atypical sensory, motor, or visual aura; confusion; dysarthria; focal neurologic deficits; gastrointestinal (GI) manifestations; or other constitutional symptoms, with or without a headache.
A detailed headache history is necessary to establish the diagnosis of migraine variants. As many as 20% of patients with migraine variant may experience prodromal symptoms without subsequent headaches. Such paroxysmal symptoms, with the recurrent attacks of transient neurologic symptoms, with or without headache, with a positive family history of migraine, and with a normal neurologic examination interictally, are confirmatory.
Interictally, the neurologic examination is nonfocal. Ictally, hemiparesis, ophthalmoplegia, or altered consciousness may be observed. Abnormalities of the oculomotor nerve with pupillary involvement are seen in ophthalmoplegic migraine, followed by abnormalities of the abducens and, less commonly, the trochlear nerve. 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.
Migraine with prolonged aura
The typical duration of a migraine aura, predominantly visual, is up to 30 minutes. In rare cases, the aura could last for as long as 60 minutes, raising concerns about possible stroke.
About 3-5% of migraineurs experience an aura without headache (acephalalgic migraine). This presentation is more common in older patients who have had a history of migraine with aura during early age. Migraine aura without headaches is suspected in patients with a history of recurrent attacks of unilateral transient monocular blindness, without risk factors for other causes of carotid disease, and with a personal or family history of migraine.
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. Acephalalgic migraine should be differentiated from transient ischemic attacks, occipital lobe seizures, and temporal lobe seizures.
Migraine variants are less recognized, less common, and less well understood than the typical migraines, both without and with aura, that usually affect children and young adults.
Affected individuals usually undergo unnecessary extensive and invasive diagnostic and laboratory evaluations before the diagnosis is made. A careful history that reveals multiple attacks with complete recovery, paroxysmal signs and symptoms with or without cephalalgia, migraine with aura—all in the absence of other medical disorders that may contribute to the symptoms—as well as a symptom-free period between attacks and a family history of migraine or a similar disorder, is usually helpful in confirming the diagnosis.
Migraine variants should be differentiated from trigeminal autonomic cephalalgias (including cluster headaches, paroxysmal hemicrania, and syndrome of neuralgiform conjunctival injection and tearing), as well as from other primary headache disorders (eg, stabbing headache, thunderclap headaches, hypnic headaches, and hemicrania continua) and primary headache syndromes associated with physical activity (eg, exertional headaches, cough headaches, and headaches associated with sexual activity).
The following conditions are included in the differential diagnosis:
Other conditions that should be considered include the following:
Cerebral autosomal dominant arteriopathy and subcortical infarcts and leukoencephalopathy (CADASIL)
Gastrointestinal motility disorders
Syncope and related paroxysmal spells
CT, MRI, and SPECT
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, single-photon emission computed tomography (SPECT) scanning might show hypoperfusion during the aura phase.
Neuroimaging with computed tomography (CT) scanning or magnetic resonance imaging (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.
Electroencephalography (EEG) is unnecessary in the management of migraine variants, except when seizure disorders must be excluded (as in migraine-triggered seizure) and when patients have 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 for familial hemiplegic migraine (FHM) can be done by using polymerase chain reaction (PCR) evaluation to detect point mutations in CACNA1A and ATP1A2; DNA sequencing is also available. Genetic testing may also be performed for other conditions associated with migraine, such as cerebral autosomal dominant arteriopathy and subcortical infarcts and leukoencephalopathy (CADASIL), an autosomal dominant disorder in which patients may present with migraine, multiple subcortical strokes, and dementia in early adulthood.
The first step in treatment is to establish the diagnosis. Once the syndromes are recognized, migraine variants respond to typical migraine preventive medications.
Treatment is divided into 3 components:
Elimination of specific triggers
Acute management of attacks
Patients should follow risk factor modifications, including smoking cessation, and they should avoid the use of hormonal replacement therapy and birth control pills, both of which could potentially increase the risk of hypercoagulability in migraineurs.
Certain food products and food additives may trigger migraine attacks in some patients. Such triggers include monosodium glutamate (MSG), nitrates-containing processed meat, aged or smoked cheese, onions, pickled products, avocados, dairy products, nuts, chocolate, caffeine, and alcoholic beverages (in particular, red wine). Identifying and avoiding individual food triggers is key in preventing migraine attacks.
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 evaluation by a gastroenterologist to exclude other gastrointestinal (GI) disorders. An evaluation by an audiologist may be necessary to exclude other vestibulopathies in patients with vertiginous migraine.
If benign coital headaches have been a problem for a significant period of time, the patient or couple may need psychological counseling.
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- Hemiplegic Migraine
- Basilar Migraine
- Childhood Periodic Syndromes
- Retinal Migraine
- Ophthalmoplegic Migraine
- Complicated Migraine
- Less Common Migraine Variants
- Differential Diagnosis
- CT, MRI, and SPECT
- Genetic Testing
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