Abstract
Background: Although the mechanism of migraine is regarded as a functional disorder of the brain, numerous studies have reported that migraine is closely associated with vascular system abnormalities.
Case reports: We describe a 19-year-old female with recurrent migraine attacks and typical aura for 7 years. MRI showed multiple stroke lesions in the posterior circulation. Moreover, a pseudoaneurysm (1.9 × 1.4 cm) originating from the left vertebral artery was observed on four-vessel angiography. Multiple microembolic signals (MES) were repeatedly observed in the basilar artery using 30-minute transcranial Doppler monitoring. Interestingly, MES and her typical migrainous symptoms disappeared simultaneously with removal of the pseudoaneurysm.
Discussion: This case supports the fact that microemboli play a pivotal role in the development of migraine attacks.
Introduction
Due to the complexity of migraine development, various theories have been suggested to understand the mechanism. The general consensus accepts migraine as a functional disorder of the brain, where a hyperexcitable brain state is susceptible to cortical spreading depression (CSD) that activates the trigeminovascular system (1). Nevertheless, there have been numerous reports focused on the association between migraine and vascular system abnormalities such as right-to-left shunt caused by a patent foramen ovale (PFO), atrial septal defect (ASD), and pulmonary arteriovenous malformation (2,3). Moreover, endothelial dysfunction, hypercoagulability, white matter hyperintensities, and altered vascular reactivity are more common in migraine sufferers (4–6).
We report a migraine patient with aura and multiple recurrent ischaemic strokes with microemboli in the posterior circulation caused by vertebral artery pseudoaneurysm. This case shows possible evidence of the pathophysiological role of microemboli in migraine development.
Case history
A 19-year-old Asian female presented to the emergency department with symptoms of nausea, vertigo, and migraine with aura. Her neurological examination was unremarkable. There was no evidence of ocular motility deficit, nystagmus, motor weakness, sensory change, and limb or truncal ataxia. The routine battery of blood tests, which included electrolyte analysis, complete blood count, a thyroid function test, coagulation factors, and erythrocyte sedimentation rate revealed no abnormalities. The patient had a past history of trauma to her left neck when she was 12 years old and a palpable neck mass on her left occipital area developed, however, she did not undergo medical evaluation. After this incident, she suffered from pulsating headaches on her left temporal area combined with nausea and vomiting, which developed after a visual aura lasting for about 30 minutes every 2–3 months. The patient described her aura as a blind spot in her visual field that initiates at the centre, gradually widens and moves to the lateral direction. Further history taking revealed that she had no family history of migraine and the patient suffered left side weakness and ipsilateral tilting when she was 18 years old. Based on previously performed MRI to evaluate her symptoms, the patient was diagnosed with migraine with aura and migrainous infarct caused by an old posterior inferior cerebellar artery (PICA) territory infarct (Figure 1A). Her symptoms are compatible with migraine with aura according to the International Headache Society (ICHD II) criteria.
(A) Previous images showing a multifocal infarct in the left PICA territory (white dashed square) on brain MRI. (B) At admission, newly developed old lesions in the posterior circulation territory (red dashed circle) on brain MRI and a benign vascular mass lesion in the left upper posterior cervical space (white arrow) on neck MRI. Four-vessel angiography revealed a mass in the left posterior cervical area that had a feeding artery arising from the left VA (red dashed square). Multiple microembolic signals (MES) in the left vertebral artery were detected during TCD monitoring (red arrows). (C) After treatment, complete obliteration of the left VA pseudoaneurysm was seen in four-vessel angiography (red dashed square) and disappearance of MES was documented in TCD monitoring. PICA = posterior inferior cerebellar artery; MRI = magnetic resonance imaging; VA = vertebral artery; TCD = transcranial Doppler; L = left; MCA = middle cerebral artery; BA = basilar artery.
The patient was on a regimen of valproate and aspirin that was prescribed intermittently since her last incident. The severity of her symptoms decreased slightly but was not controlled well. To evaluate the underlying brain parenchymal lesion and unmanaged headache, we performed MRI and MR angiography (3 T, GE Medical, USA). MRI images showed newly developed multiple infarctions on the posterior circulation compared to previous MR studies (Figure 1B). Various auto-antibody screenings such as rheumatoid factor, antinuclear, antiphospholipid and antineutrophil cytoplasmic antibodies were normal. To find the embolic source, we performed transcranial Doppler (TCD) with specialized headgear that enabled us to contemporarily monitor the anterior and posterior circulation, transthoracic echocardiography (TTE), trans-oesophageal echocardiography (TEE), and Holter monitoring. TCD monitoring showed multiple MES in the basilar artery. There was no arrhythmia, cardiac structural and functional abnormality including PFO and ASD in other studies. Four-vessel angiography revealed a mass in the left posterior cervical area that had a feeding artery arising from the left VA and there were no abnormal findings of vascular changes suggesting Takayasu’s arteritis, fibromuscular dysplasia, or other vasculitis. Neck MR showed a benign vascular mass lesion in the left upper posterior cervical space with a connection to the left VA, and we concluded this entity was most likely a pseudoaneurysm, with a differential diagnosis of haemangioma (Figure 1B). We treated the mass lesion by two-step management of coil embolization and mass removal operation. She showed no focal deficits after surgery and follow-up TCD showed no more MES (Figure 1C). The patient showed no recurrence of symptoms 6 months after surgery and has stopped the previous medication for migraine prevention.
Discussion
Because of the disappearance of microemboli and all symptoms after surgery, this case report strengthens our aforementioned hypothesis of posterior circulation microembolism playing a pivotal role in migraine with aura.
There are numerous reports on the association between migraine with aura and cardiac disease such as PFO and atrial myxoma (2,3,7). Wilmhurst et al. suggested a right-to-left shunt allows venous-circulating, migraine-triggering, as well as vasoactive chemicals to bypass the pulmonary filter and reach the cerebral circulation to induce a migraine attack (8). Paradoxical emboli appear to have a propensity for the posterior circulation, the area in which hypoperfusion occurs during a migraine with aura (9). Recent experimental data in mice indicate that small brain foci of ischaemia by cerebral microembolism triggers CSD, a putative biological substrate for migraine aura, without causing requisite tissue injury (10). CSD activates the trigeminovascular system and followed by vasodilation and neurogenic inflammation causes pulsatile headache. We presumed that focal areas of hypoperfusion by microemboli from the left VA pseudoaneurysm triggered CSD as an underlying mechanism for the attacks in this case.
Although some microemboli travel through the brain microcirculation without dire results, others can temporally occlude the circulation to a critical volume of tissue to initiate CSD followed by migraine with aura, and the risk of cerebral infarction increases with prolonged occlusion of circulation (1). In our case, we documented multiple microemboli in the basilar artery via TCD monitoring and the disappearance of those microemboli after removal of the pseudoaneurysm, and this correlated in sync with the resolution of migraine with aura and no reoccurrence of cerebral infarct. Therefore, we believe that this migraine formation and its resolution are consistent with previous experimental studies (1,10).
Conclusions
This case report suggests that microemboli can cause migraine with aura, which is probably mediated by CSD because it is a requisite component of migraine aura. We can deduce that microemboli can cause CSD in humans based on the mechanism shown in a recent mice experiment (10). We believe that this case is pictorial evidence of the role of the vascular system in migraine pathophysiology.
Footnotes
Conflict of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.