Headache, Migraine Hemiplegic

Article Editor:
Rohan Arora
Updated:
10/27/2018 12:31:37 PM
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Headache, Migraine Hemiplegic

Introduction

A hemiplegic migraine is a rare form of a migraine in which the migraine headache attack is accompanied by unilateral weakness. Typically, migraine aura has visual symptoms, but motor symptoms are rare. Hemiplegic migraine is a rare subtype of a migraine with aura, characterized by the presence of motor weakness as aura manifestation. The motor weakness is often accompanied by other forms of aura like impairment in vision, speech, or sensation. A hemiplegic migraine can run in the family (familial hemiplegic migraine) or can occur sporadically in one individual (sporadic hemiplegic migraine).

Familial Hemiplegic Migraine (FHM)

FHM is a rare, autosomal-dominant subtype of hemiplegic migraine that runs in the family. The diagnostic criteria for familial hemiplegic migraine require that at least one first or second-degree relative has had attacks fulfilling the diagnostic criteria for hemiplegic migraine.  International Classification of Headache Disorders-3 classifies FHM into 4 subtypes based on the genetic mutation associated with them.

  • FHM1 is associated with mutations in the CACNA1A gene. FHM1 is the most common type and accounts for around 50% of cases of FHM. FHM1 is commonly associated with cerebellar degeneration.
  • Mutations in the ATP1A2 gene cause FHM2, and it accounts for less than 25% of cases of FHM.
  • Mutations in the SCN1A gene cause FHM 3.
  • FHM4 is diagnosed if no known genetic mutation linked to FHM is identified.

Sporadic Hemiplegic Migraine occurs only in one individual without a family connection.

Clinical Manifestations

The characteristic feature of hemiplegic migraine is the presence of unilateral motor weakness as aura manifestation in at least some attacks. Motor weakness is however not the only type of aura present during the hemiplegic migraine attack. Other typical aura symptoms like visual field defects, scotoma, hemianopia, tingling, numbness, ataxia, fever, or lethargy can occur. Motor symptoms often start in the hand and gradually spread up into the arm and face. The unilateral weakness may switch sides between or during attacks. Rarely, patients may have a bilateral motor weakness either simultaneously or in succession. The symptoms usually occur over 20 to 30 minutes, although rarely, aura symptoms and motor weakness can develop acutely and can mimic a stroke. The symptoms can last for a few hours to days and rarely can last up to 4 weeks. The symptoms resolve completely in a majority of the cases. Most patients with hemiplegic migraine have associated headache. A headache usually occurs during the aura but can occur after the aura symptoms. Severe hemiplegic migraine attacks may be associated with encephalopathy or coma. Symptoms of severe attack including hemiplegia and impaired consciousness can last for many days to months before they resolve completely. Severe attacks can rarely cause permanent brain injury, cerebral atrophic and infarction, cognitive decline, and death.

Seizures independent of hemiplegic migraine attacks have been reported in some patients with FHM, with higher rates in families with FHM2.

Migraine attacks typically start in the first or second decade of life, with the frequency of attacks decreasing with age.

Diagnostic Criteria

Diagnostic criteria for a hemiplegic migraine as per International Classification of Headache Disorders-3 are as follows:

At least 2 attacks fulfilling the criteria 2 and 3

Aura consisting of both of the following:

  • Fully reversible motor weakness
  • Fully reversible visual, sensory and/or speech/language symptoms

At least 2 of the following 4 characteristics:

  • At least one aura symptom spreading gradually over at least 5 minutes, and/or at least 2 symptoms occurring in succession
  • Each non-motor symptom lasts 5 to 60 minutes, and motor symptoms last less than 3 days
  • At least one aura symptom is unilateral
  • Aura is accompanied or followed by a headache within 30 minutes.

No other explanation of the symptoms is available, and stroke and transient ischemic attack have been excluded.

Etiology

A hemiplegic migraine may be precipitated by acute stress, lack of sleep, excessive sleep, emotions, exertion, and head trauma. Some reports have suggested conventional angiography as a trigger for a hemiplegic migraine.

Epidemiology

A migraine is a common disorder occurring in 15% to 20% of the population. A hemiplegic migraine is a rare condition, with a reported prevalence of 0.01%. A study done in Denmark indicated the prevalence of sporadic hemiplegic migraine is 0.002% and familial hemiplegic migraine is 0.003%.

Women are 3 times more likely to be affected. The average age of onset is 12 to 17 years.

Pathophysiology

Weakness associated with a hemiplegic migraine is a manifestation of motor aura. Migraine aura is believed to be caused by a self-propagating wave of neuronal and glial depolarization that spreads across the cerebral cortex, known as cortical spreading depression.

A genetic role has been identified, especially for familial hemiplegic migraine (FHM).

  • Mutations in the CACNA1A gene, located on chromosome 19p13, cause FHM1. This gene is responsible for encoding the alpha-1A subunit of the P/Q type calcium channel. The penetrance of CACNA1 mutation ranges from 67% to 89%.
  • FHM2 is associated with mutations in the ATP1A2 gene on chromosome 1q23. This gene is responsible for encoding a catalytic subunit of sodium/potassium ATPase.
  • FHM3 is associated with mutations in the SCN1A gene on chromosome 2q24 that encodes a transmembrane alpha subunit of the brain sodium channel. Penetrance of this mutation is estimated to be 100%.
  • Some studies have associated mutation in the gene PRRT2 with familial hemiplegic migraine. More studies are needed to make this determination.

The known genetic mutations do not account for all familial hemiplegic migraine, and at least 25% of these families do not have mutations in the genes presently identified for familial hemiplegic migraine.

Some studies have suggested that 10% to 20% of sporadic hemiplegic migraine may have mutations in the CACNA1A and the ATP1A2 genes.

History and Physical

Diagnosis of a hemiplegic migraine is mostly clinical and can be challenging at times. The characteristic feature for diagnosis is episodic, reversible, unilateral motor weakness as migraine aura manifestation, along with at least one other kind of aura. It is very important to rule out other common pathologies that could potentially cause a headache and neurological deficits. A good history of symptoms, potential triggers, family history, other associated symptoms is very important for diagnosis.

Neurologic exam during an attack may show unilateral hyperreflexia and positive Babinski sign. Motor and sensory symptoms are typically more prominent in the upper extremities than lower. Exam between the attacks is typically normal. Most patients with FHM1 and few patients with FHM2 have cerebellar signs like ataxia, dysarthria, and nystagmus. SHM is rarely associated with cerebellar abnormalities.

Evaluation

Brain imaging like CT and MRI head, CSF analysis, and EEG may be required to rule out other pathologies, especially if the attacks are new in onset, have prolonged symptoms and have no family history.

Brain imaging (CT or MRI head) during attacks is usually normal. In very few cases, contralateral cortical edema and cortical or meningeal enhancement may be seen. Patients with FHM1 can have cerebral atrophy. MRI head may show cortical hemispheric atrophy and cortical laminar necrosis in severe hemiplegic migraine cases.

Cerebrospinal fluid (CSF) may show nonspecific CSF pleocytosis in few cases.

Genetic testing is not recommended in all cases. It may be useful for patients with early onset SHM associated with atypical neurologic manifestations and in patients with FHM when attack severity and neurologic manifestations diverge from other affected relatives.

Treatment / Management

Symptoms of a hemiplegic migraine can be scary and distressing. It is very important to establish a correct diagnosis and initiate proper treatment to help manage and prevent attacks.

Treatment of hemiplegic migraines involves pharmacological treatment with abortive and preventive medications. Severe attacks may need hospitalization and additional measures.

Patients with a hemiplegic migraine may be treated with the same abortive and preventive medications used for a typical migraine with aura except for agents that may exacerbate ischemia. Treatment of acute episodes is mainly with NSAIDs and antiemetics. Intranasal Ketamine given at the onset of attack has shown benefit in patients with familial hemiplegic migraine. Use of triptans for a hemiplegic migraine is controversial.

Verapamil has been used as a prophylactic and abortive agent for a hemiplegic migraine. Other drugs that have been used for prophylactic treatment include flunarizine, ketamine, lamotrigine, and naloxone. Nonrandomized studies have suggested acetazolamide may be effective as preventive medication for familial hemiplegic migraine. Initial therapy with verapamil, flunarizine or acetazolamide is recommended for patients with a hemiplegic migraine for preventive treatment. Patients who do not respond to these medications should try lamotrigine, particularly in patients who have predominant aura symptoms than a headache. Other preventive medications that can be used (like in other typical migraines with aura) are amitriptyline, topiramate, and valproic acid.

Triptans and ergotamines are usually contraindicated in a hemiplegic migraine because of concern for potential cerebral vasoconstriction. Some specialists also recommend avoidance of beta blockers as preventive therapy for patients with a hemiplegic migraine, like in a migraine with brainstem aura.

Triggers for a hemiplegic migraine headache should be identified and avoided if possible.

Differential Diagnosis

Hemiplegic migraine episode can mimic several other neurologic conditions that can cause a headache and neurological deficits. Some of the differentials include:

  • TIA (symptoms reversible in both TIA and hemiplegic migraine, but TIA symptoms are more sudden and less likely to have other aura symptoms like nausea, vomiting, photophobia, among others)
  • Infections like meningitis, encephalitis, brain abscess can cause a headache, and motor symptoms, other symptoms like rash, fever, CSF analysis, and neuroimaging can help to distinguish
  • Brain tumors typically will cause more progressive neurologic symptoms and will have neuroimaging findings
  • Seizures with postictal paralysis can be distinguished by paroxysmal symptoms like limb jerking at the onset and postictal confusion
  • Inherited disorders like MELAS and hereditary hemorrhagic telangiectasia can cause a headache, and neurologic deficits can be distinguished by clinical features, neuroimaging, and genetics
  • Metabolic disturbances like homocystinuria and ornithine transcarbamylase deficiency can rarely present with a headache and stroke-like symptoms
  • Syndrome of stroke-like migraine attacks after radiation therapy (SMART) differentiated by a history of cerebral radiation and characteristic imaging findings
  • Alternating hemiplegia of childhood

Prognosis

In most patients with a hemiplegic migraine, aura symptoms resolve completely although may be prolonged. In rare cases, hemiplegic migraine leads to permanent neurological deficits, cerebral infarctions, cognitive decline or death. Poor outcomes are often associated with early onset of a hemiplegic migraine with severe attacks, recurrent coma, or seizures. The frequency of attacks decreases after age 50 years and the hemiplegic attacks evolve into more typical migraine attacks without motor symptoms.