Objective  To study the relationship between exertion and migraine aura.

Design  Case report.

Setting  Tertiary care hospital.

Patient  A 67-year-old man presented with recurrent attacks of exertion-induced hemiplegic migraine. Since the hemiparetic attacks were exertion induced, they were initially ascribed to recurrent transient ischemic attacks. However, the clinical picture, normal findings on cerebral angiography and neuroimaging (during the period of hemiparesis), lack of response to treatment with antiplatelets and anticoagulants, and successful treatment with verapamil suggested that the hemiparesis was not due to ischemia, but was indeed a migraine aura. We suggest that exertion induced the aura of hemiparesis by lowering the threshold for the development of cortical spreading depression. Even though our patient had no family history of hemiplegic migraine, a mutation in an ion channel gene (eg, the CACNA1A gene on chromosome 19) might account for his episodic attacks.

Conclusion  Migraine aura should be included in the differential diagnosis of exertion-induced focal neurologic deficit.

It is known that exertion can aggravate migraine headache. However, the relationship between exertion and migraine aura is unknown. Exertion can induce visual aura in migraineurs,³ but, to our knowledge, aura of hemiparesis provoked by exertion has not been reported. We describe a patient who had recurrent attacks of hemiplegic migraine that were induced by exertion.

REPORT OF A CASE

After a period of severe exertion (moving furniture for 30 minutes), he had a typical attack and was admitted to the hospital. During the examination, he complained of excruciating right-sided throbbing headache and photophonophobia. His blood pressure was 129/81 mm Hg; his heart rate was 72 beats/min; and he was afebrile. The results of his general medical examination were normal. On neurologic examination, his mental status was normal. He had mild nonfluent aphasia, right-sided central facial paresis, hemiparesis (3/5), hemihypesthesia (50%), hyperreflexia, and extensor plantar response. Headache and neurologic deficits lasted for 1 day and resolved spontaneously within 1 hour. The results of the following laboratory tests and determinations were normal: complete blood cell count, general chemistry profile, coagulation studies, protein C, protein S, antithrombin III, anticardiolipin antibody, erythrocyte sedimentation rate, C-reactive protein, antinuclear antibody, serum pyruvate, serum lactate, thyroid function test, urinalysis, urinary drug screen, radiography of the chest, electrocardiography, transesophageal echocardiography, electroencephalography, computed tomography of the brain, magnetic resonance imaging with contrast (during the period of hemiparesis), and cerebral angiography. A typical attack was provoked by 20 minutes on a cardiac treadmill, but the results of the patient's cardiac and blood pressure monitoring were unremarkable. He had a mild headache, mild nonfluent aphasia, right-sided central facial paresis, hemiparesis (4/5), hemihypesthesia (75%), hyperreflexia, and extensor plantar response. His headache and neurologic deficits lasted for a few hours and resolved spontaneously within half an hour. He was treated with a combination of warfarin, aspirin, pentoxyfylline, phenytoin sodium, and amitriptyline hydrochloride for 2 years, but continued to have recurrent attacks (about 10). Subsequently, all his medications were discontinued, and he was treated with sustained-release verapamil (240 mg/d). He had complete relief of headache and hemiplegic attacks and remained asymptomatic for the following year.

COMMENT

Subsequently, the visual aura was replaced by longer-lasting episodes of hemiparesis that occurred only after exertion. Since the hemiparetic attacks were exertion induced, they were initially attributed to recurrent transient ischemic attacks.^4-5 However, the clinical picture, normal findings on cerebral angiography and neuroimaging (during the period of hemiparesis), lack of response to treatment with antiplatelets and anticoagulants, and successful treatment with verapamil suggested that the exertion-induced hemiparesis was not due to ischemia, but was in fact a migraine aura. We believe that our patient fulfilled the criteria for hemiplegic migraine, which, according to the International Headache Society, is classified under migraine with prolonged aura of hemiplegia (as opposed to familial hemiplegic migraine).^{1, 6} While our patient as well as others with hemiplegic migraine had normal findings on neuroimaging during the aura (a defining feature of a migraine aura),^1-2,6 a recent case report of abnormal gyri enhancement demonstrated on magnetic resonance imaging scans during hemiplegic migraine is intriguing and merits further investigation.⁷

Migraine aura is thought to result from cortical spreading depression (CSD).² It is not clear, however, whether additional mechanisms, such as ischemia, are required for a prolonged aura (as occurred in our patient). Although in our patient a superimposed ischemic process cannot be excluded, the clinical picture, the normal findings on cerebral angiography and neuroimaging (during the period of hemiparesis), and the lack of response to antiplatelet and anticoagulant treatment suggested that ischemia was not a major contributory factor to his prolonged aura of hemiparesis.

In our patient, exertion seemed to precipitate the aura of hemiparesis. Thus, we suggest that there is a relationship between exertion and CSD, the pathophysiological correlate of migraine aura. Exertion is associated with hyperventilation and hypocapnea, which are known to cause cerebral vasoconstriction. Hyperventilation can also cause respiratory alkalosis and hypomagnesemia.⁸ Since hypomagnesemia can also cause vasoconstriction,⁹ the transient hypomagnesemia induced by hyperventilation, combined with the primary magnesium deficiency seen in migraineurs,⁹ may lead to the known exaggerated vascular response to hypocapnea in migraineurs with aura.¹⁰ The combination of exertion-induced hyperventilation, hypocapnea, and hypomagnesemia predisposes these patients in particular to have even further cerebral vasoconstriction during exertion. In fact, frontal hypoperfusion has been observed in patients with exertional headache.¹¹ Both hypomagnesemia and hypoperfusion have been reported to lower the threshold for the development of CSD or aura in migraineurs.^{2, 12} We suggest that in our patient exertion induced the aura of hemiparesis by lowering the threshold for the development of CSD in the frontal lobe, possibly through exertion-induced frontal hypoperfusion and hypomagnesemia. This hypothesis is consistent with previous reports showing that CSD in hemiplegic migraine starts in the frontal lobe of the affected hemisphere and spreads posteriorly,¹³ unlike in typical migraine with aura, in which CSD starts in the occipital lobe and spreads anteriorly.^{3, 12-14}

Familial and sporadic hemiplegic migraine are genetically heterogeneous conditions that have been mapped to 3 different chromosome loci so far: 1 on chromosome 19 and 2 on chromosome 1.^{7, 15-17} Fifty percent of familial (17 families) and 2 cases of sporadic hemiplegic migraine are linked to at least 8 missense mutations within CACNA1A, a gene on chromosome 19 that encodes the 1A subunit of a neuronal P/Q-type calcium channel.^{7, 15-17} Currently, investigation is underway to screen our patient's DNA for mutation in the 47 exons of the CACNA1A gene. Even though our patient had no family history of hemiplegic migraine, this ion channel gene mutation might account for his episodic attack.

We are grateful to Puneet Opal, MD, PhD, Lynette Geweke, MD, Patricia Davis, MD, Henry Paulson, MD, PhD (University of Iowa, Iowa City), and Joann Jen, MD (University of California, Los Angeles), for their helpful comments.

Reprints: Mehrdad Razavi, MD, Department of Neurology, University of Iowa Hospitals and Clinics, 200 Hawkins Dr, Iowa City, IA 52242 (e-mail: Mehrdad-razavi{at}uiowa.edu).