Excerpt from Migraine Variants

Please click here to view the full topic text: Migraine Variants

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.

Please click here to view the full topic text: Migraine Variants