Aortogenic calcified cerebral embolism diagnosed with an embolus retrieved by thrombectomy: illustrative case

Abstract

BACKGROUND

Calcified cerebral embolism has been reported as a cause of acute cerebral infarction, but an aortogenic origin has rarely been identified as the embolic source. The authors describe a case of aortogenic calcified cerebral embolism in a patient with other embolic sources.

OBSERVATIONS

In a patient with cerebral infarction and atrial fibrillation, a white hard embolus was retrieved by mechanical thrombectomy. Pathological analysis of the embolus revealed that it was mostly calcified, with some foam cells and giant cells. The macroscopic and pathological findings allowed the authors to finally diagnose an aortogenic calcified cerebral embolism.

LESSONS

Even in patients with cardiogenic embolic sources, it is possible to identify a complex aortic atheroma with calcification as the embolic source, based on the macroscopic and pathological findings of the embolus retrieved by mechanical thrombectomy.

Calcified cerebral embolism has been reported as a cause of acute cerebral infarction, but an aortogenic origin has rarely been identified as the embolic source.¹ An aortogenic embolic stroke is difficult to diagnose in patients with multiple candidate embolic sources, including atherosclerotic lesions, because conventional diagnostic criteria exclude other embolic sources.² However, macroscopic and pathological findings of emboli retrieved by mechanical thrombectomy can help to identify the embolic source.³ Herein, we describe a patient with calcified cerebral embolism who had a cardiogenic embolic source. On the basis of macroscopic and pathological findings of the embolus retrieved by mechanical thrombectomy, we identified an atherosclerotic lesion with calcification as the embolic source and finally diagnosed an aortogenic calcified cerebral embolism.

Illustrative Case

History and Examination

A 71-year-old man with a history of atrial fibrillation, hypertension, and diabetes mellitus suddenly developed left-sided paralysis and was brought to our hospital by ambulance 55 minutes after onset. On admission, he had a Glasgow Coma Scale score of 14 (E4V4M6), conjugate deviation of the eyes to the right, drooping of the left corner of the mouth, dysarthria, left-sided paralysis, and a National Institutes of Health Stroke Scale score of 10. The blood biochemical test results showed hemoglobin A1c of 6.7%, glucose intolerance, low-density lipoprotein cholesterol of 131 mg/dl, and dyslipidemia. The coagulation test results showed a D-dimer level of 0.7 μg/ml, which was not elevated; activated partial thromboplastin time of 36.4 seconds; and prothrombin time-international normalized ratio of 1.90. Electrocardiography showed normal sinus rhythm. Computed tomography (CT) of the head showed a hyperdense area in the right middle cerebral artery that had not been seen 2 years earlier, with a mean density of 149 Hounsfield units (HU) and a size of 4.1 mm × 2.8 mm (Fig. 1A and B). There was an early ischemic change in the right frontal lobe, and the Alberta Stroke Program Early CT Score was 9 (Fig. 1C). CT angiography showed occlusion of the right M2 superior trunk (Fig. 1D). Because the international normalized ratio was within the range of response to warfarin, thrombectomy was started without tissue-type plasminogen activator 105 minutes after onset.

FIG. 1.

A: Axial head CT 2 years earlier showing no hyperdense area in the right middle cerebral artery (arrow). B: Axial head CT on arrival showing a hyperdense area (arrow) with a mean density of 149 HU and a size of 4.1 mm × 2.8 mm in the right middle cerebral artery. C: Axial head CT scans on arrival showing early ischemic changes in the right frontal lobe (M5). D: Head CT angiography on arrival showing occlusion of the right M2 superior trunk (arrow). E: Right internal carotid artery angiography before thrombectomy showing occlusion of the right M2 superior trunk (arrow). F: The red thrombus and white hard embolus captured with the tip of the aspiration catheter and the stent retriever. G: The retrieved embolus removed from between the tip of the aspiration catheter and the stent retriever. H: Right internal carotid artery angiography after thrombectomy showing complete recanalization of the right M2 superior trunk. I: Right common carotid artery angiography after thrombectomy showing no stenosis or contrast stagnation in the carotid artery. J: Head CT after thrombectomy showing the disappearance of the hyperdense area in the right middle cerebral artery (arrow).

Thrombectomy

A 9-French balloon guiding catheter (Optimo EPD, Tokai Medical Products) was placed in the right cervical internal carotid artery via the right femoral artery with the patient under local anesthesia. Right internal carotid angiography showed a right M2 superior trunk occlusion (Fig. 1E). A microcatheter (Phenom 21, Medtronic) and a microguidewire (Traxcess, Terumo) were guided from an aspiration catheter (Sofia flow, Terumo) through the right M1 to the occlusion. The microguidewire was relatively stiff when it passed through the occlusion, but the microcatheter passed through the lesion and was guided to the distal side of the right M2 superior trunk occlusion. A stent retriever (4 mm × 40 mm, Tron FX II, Terumo) was deployed in the right M2 superior trunk. The aspiration catheter was guided to the proximal end of the embolus in the right M2 superior trunk. The stent retriever and microcatheter were pulled into the aspiration catheter, and a small red thrombus was retrieved. However, the right M2 superior trunk remained occluded on right internal carotid arteriography.

In the second pass, the stent retriever was changed to a Solitaire X (3 mm × 40 mm, Medtronic) and was deployed in the right M2 superior trunk. The aspiration catheter was guided to the proximal end of the embolus in the right M2 superior trunk. The stent retriever and microcatheter were pulled slightly into the aspiration catheter, and then the aspiration catheter and stent retriever were retracted together into the balloon guiding catheter. A hard white embolus, 4.5 mm × 2.7 mm in size, with a red thrombus was retrieved from between the tip of the aspiration catheter and the stent retriever (Fig. 1F and G). Complete recanalization of the right M2 superior trunk (thrombolysis in cerebral infarction grade 3) was achieved 33 minutes after femoral puncture by right internal carotid angiography (Fig. 1H). Based on the macroscopic findings of the retrieved embolus, embolism due to atherosclerotic plaque in the carotid artery was suspected, but right common carotid angiography showed no evidence of stenosis or contrast stagnation in the carotid artery (Fig. 1I). Immediate postoperative head CT showed no intracranial hemorrhage, and the hyperdense area in the right middle cerebral artery seen on preoperative head CT disappeared (Fig. 1J).

Postoperative Course

Postoperatively, the left hemiparalysis was almost resolved, with mild drooping of the right corner of the mouth and dysarthria remaining. Diffusion-weighted imaging of the head on the day after surgery showed an acute infarct in the right insular gyrus and frontal operculum (Fig. 2A), and magnetic resonance angiography of the head confirmed recanalization of the right M2 superior trunk without stenosis (Fig. 2B). CT angiography of the head 2 days after surgery showed recanalization of the right M2 superior trunk without stenosis (Fig. 2C). CT angiography of the aortic arch and the cervical portion showed minimal calcification at the origin of the internal carotid artery and a complex aortic atheroma with an irregular surface and calcification with a maximum thickness of 5.2 mm in the aortic arch (Fig. 2D–F). Contrast-enhanced CT of the trunk showed a focal area of acute ischemia in the right renal parenchyma. Cervical magnetic resonance imaging showed no carotid atheroma as an embolic source (Fig. 2G). There was high signal on T1-weighted magnetic resonance imaging of the aortic arch, consistent with the complex aortic atheroma on CT angiography (Fig. 2H). CT angiography of the heart showed very mild calcification of the aortic valve (Fig. 2I). To prevent cerebral embolism associated with atrial fibrillation, the patient was started on edoxaban 10 mg/day from 6 days after surgery when the PiCT decreased to less than 1.6. Pathological findings showed calcification in most of the retrieved embolus, with fibrin precipitation, foam cells, and giant cells mainly at the margins (Fig. 3). Transesophageal echocardiography also showed a complex aortic atheroma with an irregular surface and calcification, and blood flow velocity measurements showed regurgitation with a maximum velocity of 40 cm/s during diastole (Fig. 4). Based on the retrieved embolus and imaging studies, a diagnosis of aortogenic calcified cerebral embolism was made. Because the patient had atrial fibrillation, anticoagulant therapy was continued as secondary prevention antithrombotic therapy. Furthermore, a potent statin was introduced, and risk factors, including diabetes mellitus, were strictly controlled. On the 25th day, the patient was discharged home with a modified Rankin Scale score of 1 with only mild left upper-limb motor dysfunction and residual left facial palsy. The 90-day modified Rankin Scale score was 0, and there was no evidence of recurrent stroke at the 6-month postoperative follow-up.

FIG. 2.

A: Diffusion-weighted imaging showing an acute infarct in the right insular gyrus and frontal operculum. B: Magnetic resonance angiography showing recanalization of the right M2 superior trunk without stenosis. C: Head CT angiography showing recanalization of the right M2 superior trunk without stenosis. D–F: Aortic arch and neck CT angiography showing a complex atheroma with a maximum thickness of 5.2 mm with an irregular surface and calcification in the aortic arch and very little calcification at the origin of the right internal carotid artery. G: Cervical magnetic resonance imaging showing no carotid plaque as an embolic source. H: Aortic arch T1-weighted magnetic resonance imaging showing atherosclerotic plaque with hyperintensity on the lesser curvature side of the aortic arch. I: Cardiac CT showing minimal calcification of the aortic valve.

FIG. 3.

Pathological findings of the retrieved embolus. Hematoxylin and eosin staining (A–C) showing that most of the embolus was calcified, with fibrin precipitation, foam cells, and giant cells mainly at the margins. Panels B and C are enlarged views of the rectangular areas in panel A.

FIG. 4.

A: Blood flow velocity in the aortic arch. The upper waveform of the horizontal line shows the systolic antegrade blood flow, and the lower waveform of the horizontal line shows the diastolic retrograde blood flow. B: A complex aortic atheroma with an irregular surface and calcification with a maximum thickness of 5.2 mm is seen on the lesser curvature side of the aortic arch. C: Systolic color Doppler showing antegrade blood flow. D: Diastolic color Doppler showing retrograde blood flow.

Patient Informed Consent

The necessary patient informed consent was obtained in this study.

Discussion

Observations

In cases with multiple embolic sources, including atherosclerotic lesions, the macroscopic and pathological findings of the retrieved thrombus may be useful in identifying the embolic source. Although there have been several reports of mechanical thrombectomy for calcified cerebral embolism,^4–7 to our knowledge, this is the first case in which the embolic source was identified on the basis of macroscopic and pathological findings of the retrieved embolus.

The patient in our case had a complex atheroma with calcification in the aortic arch but did not meet the current diagnostic criteria for aortogenic embolic stroke, because he had a cardiogenic embolic source.² A complex atheroma with calcification in the aortic arch was observed on CT angiography, and transesophageal echocardiography and aortic magnetic resonance imaging showed findings suggestive of a vulnerable area in the same calcified area. Aortic arch lesions distal to the carotid bifurcation are known to be an embolic source due to regurgitation from the descending aorta during diastole, even in the presence of a normal aortic valve,⁸ and we suspected this lesion to be an embolic source. Although it has been shown that 35% of patients with atrial fibrillation have a complex aortic atheroma,⁹ it is difficult to identify a true embolic source because the current diagnostic criteria for aortogenic embolic stroke are as follows: 1) magnetic resonance imaging findings suggestive of embolism, 2) a complex aortic atheroma ≥4 mm thick in the aortic arch on transesophageal echocardiography, and 3) a diagnosis of aortogenic embolic stroke in the absence of other embolic causes.² Pathological findings of thrombi retrieved by mechanical thrombectomy have been reported to differ depending on the etiology of the stroke.^10–12 In addition, pathological identification of foam cells in the thrombus is one of the findings strongly suggestive of atheromatic embolism, including aortogenic cerebral embolism.¹³ In the present case, the diagnosis of aortogenic embolic stroke was based on the macroscopic and pathological findings of the retrieved embolus rather than on conventional diagnostic criteria.

In cases of suspected calcified embolism, the combined technique may be the most effective means of thrombus retrieval. Calcified cerebral embolism is an intracranial embolism caused by calcified material and accounts for approximately 3% of ischemic strokes; however, 30% of these cases are misdiagnosed as vascular calcification, microbleeding, or infection on initial imaging.¹ The imaging characteristics of calcified emboli on CT are described as spherical or oval with a mean thickness of 2.5 mm (1.0–5.5 mm) and 162 HU (79–435 HU). In the present case, the preoperative CT findings were consistent with the characteristics described above, and calcified cerebral embolism was suspected preoperatively on the basis of CT findings 2 years earlier. Even in the absence of prior imaging, the possibility of a calcified cerebral embolism and atherosclerotic changes in the affected vessels themselves should be considered when severe calcification is observed along the vessel course and ischemic foci are found in the distal vascular territory. Mechanical thrombectomy using an aspiration catheter alone or a stent retriever alone for calcified cerebral embolism is known to have a worse clinical outcome than that for conventional embolism due to a red thrombus because of its lower effective recanalization rate. On the other hand, the combined technique using a stent retriever and aspiration catheter for calcified emboli in acute ischemic stroke has been reported to achieve a higher effective recanalization rate in calcified cerebral embolism than using a stent retriever alone.^4,5 In an in vitro study of calcified cerebral emboli, the combined technique using a stent retriever and aspiration catheter was shown to be the most effective in retrieving the calcified embolus compared with either a stent retriever or an aspiration catheter alone.¹⁴ In the present case, an attempt to retrieve the embolus by pulling the stent retriever into the aspiration catheter was unsuccessful in the first pass. This is because the calcified embolus in this case was four to five times stiffer than conventional red thrombi.¹⁵ If the embolus were larger than the lumen of the aspiration catheter, it would have been difficult to pull it into the aspiration catheter. In the second pass, the embolus was retrieved by simultaneously pulling the stent retriever and aspiration catheter.

It has been reported that 43% of calcified cerebral embolisms recur,¹ requiring appropriate secondary preventive treatment based on identification of the embolic source. The American Heart Association/American Stroke Association guidelines for occult stroke do not recommend surgical treatment for secondary prevention.¹⁶ In calcified cerebral embolism, antithrombotic therapy may not be effective, because cerebral embolism occurs when the calcified surface is exposed and calcium grains are dispersed.¹⁷ On the other hand, anticoagulant therapy has been reported to be effective in preventing recurrent embolic strokes in patients with atrial fibrillation who have complex aortic atheroma.¹⁰ The optimal antithrombotic therapy for aortogenic cerebral embolism in patients with atrial fibrillation remains controversial.¹⁸ A retrospective study of complex aortic atheroma showed that potent statins were effective in preventing recurrent cerebral embolism.⁶ In the present case, the patient had atrial fibrillation, so anticoagulant therapy was continued and a potent statin was introduced to strictly control risk factors.

Lessons

Even in patients with cardiogenic embolic sources, it is possible to identify a complex aortic atheroma with calcification as the embolic source, based on the macroscopic and pathological findings of the embolus retrieved by mechanical thrombectomy.

Acknowledgments

We thank Miho Kobayashi for English language editing.

Author Contributions

Conception and design: Ikeda, Yokochi, Osuki. Acquisition of data: Ikeda, Yokochi. Analysis and interpretation of data: Ikeda, Yokochi. Drafting the article: Ikeda, Yokochi. Critically revising the article: Ikeda, Yokochi, Osuki. Reviewed submitted version of manuscript: Ikeda, Yokochi, Uezato, Kinosada, Kurosaki. Approved the final version of the manuscript on behalf of all authors: Ikeda. Administrative/technical/material support: Ikeda, Yokochi, Tanimura, Chin. Study supervision: Chin.