Mechanical Thrombectomy for N-butyl-2 Cyanoacrylate Cerebral Embolism via Portopulmonary Venous Anastomosis Following Endoscopic Injection Sclerotherapy: A Case Report

Ichiro MAEDA; Taichiro IMAHORI; Shigeru MIYAKE; Hiroki GOTO; Rikuo NISHII; Haruka ENAMI; Daisuke YAMAMOTO; Shouichi NAKAYASU; Hirotoshi HAMAGUCHI; Naokazu MIYAMOTO; Takashi SASAYAMA

doi:10.2176/jns-nmc.2025-0076

Abstract

Cerebral embolism following endoscopic injection sclerotherapy using N-butyl-2 cyanoacrylate for esophagogastric varices is a rare but serious complication. This condition occurs due to the migration of N-butyl-2 cyanoacrylate into the cerebral circulation, which has traditionally been attributed to paradoxical embolism via a patent foramen ovale. However, recent reports have suggested the possibility of alternative embolic pathways. We report the case of a 76-year-old woman who presented with acute gastric variceal bleeding and underwent endoscopic injection sclerotherapy using N-butyl-2 cyanoacrylate and Lipiodol. Shortly after the procedure, the patient developed global aphasia and right hemiparesis. Head computed tomography revealed scattered ultra-hyperdense materials and magnetic resonance imaging confirmed left middle cerebral artery M2 occlusion. Mechanical thrombectomy was performed, achieving successful recanalization and neurological improvement. Imaging findings and histopathological analysis of the retrieved thrombus strongly supported the diagnosis of N-butyl-2 cyanoacrylate embolism. Retrospective evaluation of preoperative contrast-enhanced computed tomography identified a portopulmonary venous anastomosis, a right-to-left shunt connecting gastric varices to the pulmonary veins. This anastomosis is a collateral pathway associated with portal hypertension. This case suggests that even in the absence of a patent foramen ovale, portopulmonary venous anastomosis can serve as a route for N-butyl-2 cyanoacrylate migration into the cerebral circulation. To the best of our knowledge, this is the first reported case of mechanical thrombectomy for N-butyl-2 cyanoacrylate cerebral embolism following endoscopic injection sclerotherapy. This case underscores the importance of early detection and risk assessment of such right-to-left shunting and highlights mechanical thrombectomy as a viable intervention for cases where thrombolysis is contraindicated.

Introduction

Rupture of esophagogastric varices is a life-threatening complication of portal hypertension, with approximately one-third of cirrhotic patients succumbing to variceal hemorrhage.¹⁾ Endoscopic injection sclerotherapy (EIS) is a well-established hemostatic treatment, and N-butyl-2-cyanoacrylate (NBCA) is widely used as a sclerosing material.²⁾ However, NBCA injection carries a risk of systemic embolization, which, though occurring in less than a few percent of cases, can lead to severe complications.³⁾

Among systemic embolisms, cerebral embolism is an extremely rare but critical complication, with an estimated incidence of less than 0.2%.³⁾ Traditionally, NBCA-related cerebral embolism following EIS has been reported as a consequence of paradoxical embolism via a patent foramen ovale (PFO).⁴^-⁸⁾ However, recent reports suggest an alternative embolic pathway involving portopulmonary venous anastomosis (PPVA), a collateral circulation associated with portal hypertension. PPVA functions as a right-to-left shunt, potentially allowing NBCA migration into the cerebral circulation.⁹^,¹⁰⁾ Despite its potentially significant neurological implications, the clinical characteristics and optimal management strategies for NBCA-related cerebral embolism remain insufficiently understood.

In this report, we present a case of left middle cerebral artery (MCA) M2 occlusion due to NBCA cerebral embolism via PPVA following EIS, which was successfully recanalized by mechanical thrombectomy. To the best of our knowledge, this is the first reported case of mechanical thrombectomy performed for NBCA embolism following EIS.

Case Report

Case presentation

A 76-year-old woman with a history of cryptogenic liver cirrhosis (undiagnosed by biopsy) and untreated gastric varices had been under regular follow-up at a local clinic. The patient was emergently transported to our hospital due to hematemesis. On initial examination, the patient was alert with no apparent neurological deficits. However, the patient was in hemorrhagic shock, presenting with a systolic blood pressure of approximately 60 mmHg, a pulse rate of about 120 bpm, and a hemoglobin level of 8 g/dL. Abdominal computed tomography (CT) and upper gastrointestinal endoscopy confirmed active bleeding from ruptured gastric varices. The patient's Child-Pugh classification at admission was 9 points (class B).

Emergency EIS was performed while administering a blood transfusion for anemia. Under intravenous sedation, a 77% NBCA solution (Histoacryl 1.0 mL mixed with Lipiodol 0.3 mL) was injected in 2 separate sessions, with a total volume of 2.6 mL, successfully achieving hemostasis. However, immediately postprocedure, the patient developed right conjugate gaze deviation, global aphasia, and right hemiparesis, with a National Institutes of Health Stroke Scale score of 25. Head CT revealed scattered ultra-hyperdense materials, highly suggestive of NBCA embolism (Fig. 1A and B). Magnetic resonance imaging (MRI) confirmed left MCA M2 occlusion and multiple acute ischemic lesions (Fig. 1C and D).

Fig. 1

Preprocedural and procedural imaging.

After EIS using NBCA and Lipiodol for gastric varices, the patient developed right hemiparesis and aphasia. Head CT revealed an ultra-hyperdense material in the left MCA (M2) (arrow) and multiple scattered hyperdense foci in the intracranial arteries (*), suggestive of NBCA embolism (A, B). MRA demonstrated poor visualization of the left M2 and its distal branches, indicating arterial occlusion (C). MR DWI revealed an acute infarction corresponding to the M2 inferior branch territory (D). Emergency cerebral angiography confirmed an occlusion of the left M2 segment. The upper row of images (E, F) presents lateral whole-view projections, while the lower row shows magnified frontal projections. The occlusion was identified as an incomplete obstruction at the M2 segment origin due to an embolus (arrow) (E). Mechanical thrombectomy was performed using an aspiration catheter (arrow) (F), successfully achieving recanalization of the MCA M2 segment (arrow) (G).

CT: computed tomography; DWI: diffusion-weighted imaging; EIS: endoscopic injection sclerotherapy; MCA: middle cerebral artery; MR: magnetic resonance; MRA: magnetic resonance angiography; NBCA: N-butyl-2 cyanoacrylate

Endovascular procedure

Given the presence of an ischemic penumbra within the territory of the left MCA M2 occlusion, the patient was considered a suitable candidate for revascularization therapy, and mechanical thrombectomy was initiated 90 mins after symptom onset. Initial cerebral angiography demonstrated an incomplete occlusion of the left M2 segment due to a thrombus (Fig. 1E). Mechanical thrombectomy was performed with the RED 72 reperfusion catheter (Penumbra, Alameda, CA, USA) (Fig. 1F). A single-pass aspiration successfully removed the thrombus, leading to successful recanalization 40 mins after arterial puncture (Fig. 1G).

Postprocedural course

After recanalization, the patient's severe sensory-dominant aphasia and apraxia persisted as residual deficits. However, significant improvement in motor function was observed. Before thrombectomy, the patient had near-complete paralysis of the right upper and lower limbs. By the time of discharge, the Brunnstrom stage had improved to V in the right upper limb, V in the right lower limb, and IV in the fingers, indicating marked motor recovery.

Postoperative head CT revealed that the hyperdense material at the M2 origin, presumed to be the Lipiodol component of the sclerosing agent, had disappeared (Fig. 2A and B). Postoperative brain MRI showed a slight increase in infarct size compared to preoperative imaging but confirmed successful recanalization of the previously occluded vessel (Fig. 2C and D).

Fig. 2

Postprocedural imaging and thrombus histology.

Postoperative CT confirmed that the hyperdense material at the M2 origin of the left MCA had disappeared (arrow), although other scattered hyperdense signals persisted (*), with surrounding areas of hypodensity indicating infarction (A, B). Postoperative MRA demonstrated improved blood flow signals beyond the M2 segment (C). DWI showed more pronounced infarct lesions in the left temporal and occipital lobes (D). The retrieved thrombus is displayed in a macroscopic photograph (E) and histological analysis (F, G). Hematoxylin-eosin staining (original magnification: F, ×20; G, ×200) revealed that the thrombus was composed of fibrin and red blood cells, with a pale background matrix, distinguishing it from a typical fibrin thrombus.

CT: computed tomography; DWI: diffusion-weighted imaging; MCA: middle cerebral artery; MRA: magnetic resonance angiography

The retrieved thrombus was firm and fibrous on macroscopic examination, while histopathological analysis identified fibrin as the main component, with a pale background matrix (Fig. 2E-G). These findings strongly indicate that the cerebral arterial embolism resulted from the migration of the sclerosing agent, a mixture of NBCA and Lipiodol, into the cerebral circulation.

Postoperative transthoracic echocardiography did not detect a PFO. However, retrospective evaluation of preoperative contrast-enhanced CT revealed a PPVA (Fig. 3A and B). In this case, PPVA was identified as the likely route through which NBCA migrated to the cerebral arteries during EIS. The patient was transferred to a rehabilitation hospital on postoperative day 26.

Fig. 3

Preprocedural contrast imaging and embolization pathway.

Contrast-enhanced CT obtained before EIS (A) and a schematic illustration of the PPVA (B). The prominent intramural gastric varices are clearly visible. A PPVA (arrow) between the draining gastric veins and the left pulmonary vein is observed, forming a right-to-left shunt, which serves as the pathway for NBCA migration from gastric varices into the cerebral circulation. Note: This CT image was obtained before the current EIS procedure. The hyperdense areas in the gastric variceal wall represent calcifications, while the hyperdense regions in the PPVA and pulmonary vein are CT motion artifacts, not NBCA casts.

CT: computed tomography; EIS: endoscopic injection sclerotherapy; NBCA: N-butyl-2 cyanoacrylate; PPVA: portopulmonary venous anastomosis

Discussion

Summary of the case

This case highlights a rare instance of NBCA-related cerebral embolism following EIS for gastric varices, in which mechanical thrombectomy successfully restored blood flow. Unlike previously reported cases linked to paradoxical embolism via a PFO, this case identified PPVA as the most likely embolic pathway. This finding suggests that PPVA should be considered as a potential risk factor for systemic embolization in patients undergoing EIS.

PPVA as an alternative embolic pathway

Several case reports have documented ischemic stroke as a complication of NBCA use in EIS (Table 1).⁴^-¹⁰⁾ The most commonly reported mechanism has been paradoxical embolization via a PFO.⁴^-⁸⁾ However, recent reports have identified PPVA as an alternative route.⁹^,¹⁰⁾ PPVA is a collateral channel that connects peri-esophageal veins, an alternative drainage route of the left gastric vein, to the right or left pulmonary veins (Fig. 3B).¹¹⁾ Unlike other portosystemic collateral pathways, which connect to the systemic circulation, PPVA links to the pulmonary circulation, functioning as a right-to-left shunt.¹¹⁾ The reported prevalence of PPVA in portal hypertension ranges from 1% to 33%, with its increasing recognition due to advancements in imaging techniques.¹²^-¹⁶⁾

Table 1

Summary of Reported Cases of Embolic Stroke After Endoscopic Injection Sclerotherapy for Gastroesophageal Varices

Author (year)	Age/ gender	Target disease	Injection materials	Neurological symptoms	Estimated pathway of embolic stroke	Treatment for embolic stroke
F: female; M: male; NBCA: N-butyl-2-cyanoacrylate; PFO: patent foramen ovale; PPVA: portopulmonary venous anastomosis
Roesch (1998)	66/F	Ruptured gastric varices	NBCA and lipiodol	Consciousness disturbance	Pulmonary arteriovenous shunt	Observation
Upadhyay (2005)	65/M	Ruptured gastric varices	NBCA and lipiodol	Cortical blindness	PFO	Observation
Appenrodt (2006)	68/F	Ruptured gastric varices	NBCA and lipiodol	Cortical blindness hemiparesis	PFO	Observation
Abdullah (2009)	40/M	Ruptured esophageal varices	NBCA and lipiodol	Cortical blindness hemiparesis	PFO	Observation
Abbar (2018)	52/M	Ruptured duodenal varices	NBCA and lipiodol	Aphasia hemiparesis	PFO	Observation
Power (2019)	25/F	Ruptured gastroesophageal varices	NBCA and lipiodol	Neurological deficits	PPVA	Observation
Wang (2019)	45/M	Ruptured gastric varices	NBCA and polidocanol	Aphasia hemiparesis	PPVA	Observation
Talerico (2021)	18/M	Ruptured gastroesophageal varices	NBCA and lipiodol	Aphasia hemiparesis	PFO	Observation
Present case	76/F	Ruptured gastric varices	NBCA and lipiodol	Aphasia hemiparesis	PPVA	Mechanical thrombectomy

Diagnostic considerations and risk reduction strategies

This case highlights the importance of preoperative imaging evaluation for detecting PPVA, as its identification may prevent systemic embolization. With recent advancements in diagnostic imaging, preoperative assessment of PPVA has become feasible.¹⁴^,¹⁵⁾ Additionally, several factors are associated with an increased risk of NBCA embolization, including large-volume injection, slow administration, and a high Lipiodol dilution ratio.³^,¹⁷⁾ If PPVA is detected preoperatively, several measures can reduce the risk of embolization, including fluoroscopic guidance during sclerotherapy, adjusting sclerosing agent concentration, controlling injection speed, and incorporating adjunctive coil embolization.³^,¹⁷^-¹⁹⁾

Treatment challenges and role of mechanical thrombectomy

When NBCA embolizes a major cerebral artery, no widely established effective treatment has been available. Given that these patients primarily present with acute bleeding, thrombolytic therapy is contraindicated.⁸⁾ As a result, most previously reported cases have been managed conservatively.⁴^-¹⁰⁾ Previous reports have demonstrated the efficacy of mechanical thrombectomy for iatrogenic NBCA migration into cerebral arteries during neurovascular procedures.²⁰⁾ Similarly, in this case, we successfully aspirated and retrieved the NBCA embolism that had migrated into the cerebral arteries using a thrombectomy device. To the best of our knowledge, this is the first reported case in which mechanical thrombectomy successfully treated NBCA embolism following EIS. Given the lack of alternative treatment options, mechanical thrombectomy may represent the only viable intervention for similar cases of NBCA-induced cerebral artery occlusion.

Conclusions

This case highlights a rare instance of NBCA-related cerebral embolism following EIS, where PPVA, rather than PFO, was the likely embolic pathway. Given its right-to-left shunting nature, preoperative imaging is crucial to prevent systemic embolization. Mechanical thrombectomy successfully restored blood flow, emphasizing its role as a viable intervention when thrombolysis is contraindicated.

Acknowledgments

The authors thank Dr. Yuki Yamamoto for assistance with the interpretation of the pathology findings.

Funding

Part of this research was supported by the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (JSPS KAKENHI grant numbers 21KK0289 and 23K15668).

Ethical Considerations

This study is a retrospective case report and does not require ethical approval, in accordance with the institutional guidelines. Written informed consent for the academic use of medical data, including imaging, was obtained from the patient.

Consent to Participate

Written informed consent to treatment was obtained from the patient.

Consent for Publication

Written informed consent for publication was obtained from the patient.

Data Availability

The data presented in this study are available on request from the corresponding author.

Conflicts of Interest Disclosure

All authors have no conflict of interest.

References

Corresponding author

Register with J-STAGE for free!