Radiol Oncol 2020; 54(2): 144-148. doi: 10.2478/raon-2020-0017 144 review Mechanical recanalization for acute bilateral cerebral artery occlusion – literature overview with a case Miran Jeromel1,2, Zoran V. Milosevic1, Janja Pretnar Oblak3 1 Department of Diagnostic and Interventional Neuroradiology, University Medical Centre Ljubljana, Ljubljana, Slovenia 2 Department of Diagnostic and Interventional Radiology, General Hospital Slovenj Gradec, Slovenj Gradec, Slovenia 3 Department for Vascular Neurology and Intensive Neurological Therapy, University Medical Centre Ljubljana, Ljubljana, Slovenia Radiol Oncol 2020; 54(2): 144-148. Received 19 January 2020 Accepted 5 March 2020 Correspondence to: Miran Jeromel, M.D., Ph.D., Department of Diagnostic and Interventional Radiology, General Hospital Slovenj Gradec, Gosposvetska cesta 1, SI-2380 Slovenj Gradec, Slovenia. E-mail: miran.jeromel@gmail.com Disclosure: No potential conflicts of interest were disclosed. Background. Acute bilateral internal carotid artery (ICA) and/or middle cerebral artery (MCA) occlusion is extremely rare and associated with poor clinical outcomes. There are only a few reports in the literature about mechanical thrombectomy being performed for acute bilateral occlusions. The treatment strategies and prognoses (clinical out- comes) are therefore unclear. Methods. A systematic review of the literature was performed through several electronic databases with the follow- ing search terms: acute bilateral stroke, mechanical recanalization and thrombectomy. Results. In the literature, we identified five reports of six patients with bilateral ICA and/or MCA occlusion treated with mechanical recanalization. Additionally, we report our experience with a subsequent contralateral large brain artery occlusion during intravenous thrombolytic therapy, where the outcome after mechanical thrombectomy was not dependent on the time from stroke onset but rather on the capacity of collateral circulation exclusively. Conclusions. Acute bilateral cerebral (ICA and/or MCA) occlusion leads to sudden severe neurological deficits (comas) with unpredicted prognoses, even when mechanical recanalization is available. As the collateral capacity seems to be more important than the absolute time to flow restoration in determining the outcomes, simultaneous thrombectomy by itself probably does not lead to improved functional outcomes. Key words: acute bilateral stroke; mechanical recanalization; thrombectomy Introduction Acute embolic bilateral internal carotid artery (ICA) and/or middle cerebral artery (MCA) occlu- sion leads to sudden comas with poor prognoses.1-9 The reported incidence of this condition in stroke patients treated with intravenous or intra-arterial therapy is 0.34%.8 There are few reports on the en- dovascular treatment (mechanical recanalization – thrombectomy) of this rare condition. The treat- ment strategies and prognoses (clinical outcomes) are therefore unclear. The aim of the present article was to discuss our experience with the treatment of this severe condi- tion through a few published reports. To the best of our knowledge, we report the first case of sub- sequent contralateral large brain artery occlusion during intravenous thrombolytic therapy, where the outcome after mechanical thrombectomy was not dependent on the time from stroke onset but Radiol Oncol 2020; 54(2): 144-148. Jeromel M et.al. / Acute bilateral cerebral artery occlusion 145 rather on the capacity of collateral circulation ex- clusively. Methods A systematic review of the literature was per- formed through several electronic databases: PubMed (US National Library of Medicine, http://www.ncbi.nlm.nih.gov/pubmed), Google Scholar (https://scholar.google.com/), Scopus (Elsevier, http://www.scopus.com/), DeGruyer (https://www.degruyer.com) and Cochrane Library (http://www.cocranelibrary.com). The following search terms were used: acute bilateral stroke, me- chanical recanalization and thrombectomy. Results Altogether, five reports of six patients with bilat- eral ICA and/or MCA occlusion that met the inclu- sion criteria were identified (Table 1). Four patients were females (age range 64–78 years), one was male (72 years), and one was a middle-aged patient of an undetermined sex. All patients were treated with mechanical recanalization (thrombectomy) using different endovascular techniques (stent re- triever, aspiration or a combination of both). Flow in the occluded artery was completely or partially restored in all cases. The clinical outcome ranged from complete recovery (without neurological def- icits) to a coma (a fatal outcome). We present a case of a 77-year-old female patient with a medical history of hypertension, diabetes mellitus type 2, hyperlipidaemia and atrial fibril- lation who was admitted to the general hospital with an acute onset of left-sided hemiplegia and dysarthria (National Institutes of Health Stroke Scale [NIHSS]: 4, Modified Rankin Scale [mRS]: 3). The patient was last seen without deficits 80 min- utes prior to admission. The initial computed to- mography (CT) scan revealed no ischaemic brain damage, and CT angiography showed right M1 MCA occlusion (Figure 1). Intravenous thromboly- sis (IVT) was administered after 173 minutes and discontinued due to the sudden loss of conscience, the deviation of the head toward the left side and tonic-clonic spasms of the left extremities. The con- trol CT scan performed under general anaesthesia TABLE 1. Comparing 6 reported cases of mechanical thrombectomy in acute bilateral ICA and/or MCA occlusions Author, (Year), Clinical presentation Sex/age (years) Site of occlusion Mechanical thrombectomy (technique) Clinical outcome reference ICA MCA Dietrich et al. (2014)5 left hemiparesis, progressing to coma M/72 - + (M1) aspiration+stent- retriever minor deficit Pop et al. (2014)6 impaired consciousness F/78 + + (M2) stent-retriever no deficit Pop et al. (2014)6 right sided weakness F/66 + + (M1) stent-retriever severe deficit Braksick et al. (2018)7 coma F/76 - + (M1) - (no data) coma Larrew et al. (2019) 8 coma - (no data) / middle age + + - aspiration fatal Storey et al. 2019)9 hemiparesis / hemiplegia F/64 + + (M1,M2) aspiration+stent-retriever minor deficit F = female; ICA = internal carotid artery; M = male; MCA = middle cerebral artery FIGURE 1. Initial imaging workup upon arrival at the general hospital. CT angiography (CTA) shows right M1 occlusion (arrow). Radiol Oncol 2020; 54(2): 144-148. Jeromel M et.al. / Acute bilateral cerebral artery occlusion146 showed no haemorrhagic complications. Since it was assumed that the patient had a symptomatic epileptic seizure, IVT was continued. The sedated patient was immediately transported to a tertiary institution, where a multimodal CT protocol (na- tive CT scan, CT angiography [CTA] and CT per- fusion imaging [CTP]) was performed, and the results revealed no signs of ischaemic brain dam- age in the symptomatic right cerebral hemisphere despite the presence of M1 occlusion and subtle (newly appeared) signs of irreversible brain dam- age in the contralateral MCA territory due to left ICA (“T”) occlusion. It was obvious that an addi- tional embolic occlusion occurred during the IVT treatment. Although the time of occlusion was long, the CTP imaging results showed a penumbra in the right MCA territory and not in the contralat- eral left MCA territory, where irreversible brain damage occurred within 3 hours (Figure 2). Conventional (digital subtraction) angiography confirmed right MCA occlusion with good collat- eral flow provided by the right anterior cerebral artery (ACA). However, the situation on the left side had changed. Namely, a complete recanaliza- tion of the carotid “T” occlusion was seen angio- graphically as a consequence of thrombolysis and distal migration of the thrombembolus (now pre- senting with proximal M2 segment occlusion of the major MCA branch). However, no collateral flow was observed despite complete left ACA patency (Figure 3). Endovascular mechanical recanaliza- tion with aspiration was successfully performed on the right side (Figure 4A). The same procedure was not performed on the left side because there was irreversible brain damage in the whole occluded arterial territory and a high risk of haemorrhagic complications. The postprocedural thrombolysis in cerebral infarction (TICI) scores were 3 (right MCA) and 2b (left MCA). The control CT and magnetic resonance imaging (MRI) scans performed on the next and subsequent days revealed no ischaemic damage on the right side and acute ischaemic stroke in the correspond- ing left MCA territory (Figure 4B). The patient was discharged with an improved clinical condition. However, severe neurological deficits (global dys- phasia, dysarthria, spastic hemiplegia of the right limbs) were a consequence of permanent brain damage on the left side (NIHSS 5, mRS 5). Discussion To the best of our knowledge, there are only six reports about mechanical thrombectomy being performed for acute bilateral ICA and/or MCA occlusions.5-9 A 2014 report by Dietrich et al. de- scribes two M1 MCA thrombectomy procedures being performed in sequence. Aspiration was at- tempted without success, so multiple passes with FIGURE 2. (A) Control images taken in the general hospital after clinical deterioration during intravenous thrombolysis and before the transfer to the tertiary institution. There were still no signs of ischaemic brain damage in the right cerebral hemisphere but there were subtle signs of stroke in the left middle cerebral artery (MCA) territory (white line delineates loss of cortical grey matter – white matter differentiation in the frontoparietal lobe with sulcal effacement). (B) Control images taken in the general hospital after clinical deterioration during intravenous thrombolysis and before the transfer. CT angiography (CTA) showed persistent right M1 occlusion (black arrow) but also left carotid “T” occlusion (white arrow). (C) Control images taken in the general hospital after clinical deterioration during intravenous thrombolysis and before the transfer. CT perfusion imaging (CTP) showed a penumbra in the right MCA territory (black circle) and irreversible brain damage in the left MCA territory (white circle). A B C Radiol Oncol 2020; 54(2): 144-148. Jeromel M et.al. / Acute bilateral cerebral artery occlusion 147 stent retrievers were performed for successful re- canalization.5 Another report from the same year (2014) by Pop et al. demonstrates two cases for which ICA-MCA (M1, M2) bilateral thrombectomy procedures with stent retrievers were successful.6 A recent report by Larrew et al. (2019) describes a novel successful method for bilateral ICA occlu- sion, simultaneous recanalization, which utilizes two interventionalists and technicians simultane- ously for aspiration thrombectomy.8 In the latest report by Storey et al. (2019), sequential M1-M2 MCA mechanical thrombectomy was successfully performed using a combination of the stent re- triever and aspiration techniques.9 A case of stroke similar to that described in our study was reported by Braksick et al. (2018), where M1 MCA occlusion also occurred during the thrombolytic treatment of contralateral M1 MCA occlusion. Despite attempts at clot retrieval, flow was not completely restored, and the patient remained comatose.7 As so few related cases have been reported, it is unclear whether the outcomes can be improved by the optimization of the assessment and endovascu- lar approach.10 A comparison of our case with the abovementioned cases shows that the initial clinical presentations are similar, as they are cases of rapid deterioration with a loss of conscience. A prompt, adequate workup and treatment (a successful combination of standard care and mechanical re- canalization) have led to clinical improvements and minimize morbidity and mortality.9 However, the clinical outcomes reported in the literature are still diverse.5-9 It is unclear whether simultaneous thrombectomy, as described by Larrew et al.8, can improve the outcome by means of faster recanali- zation. The answer can possibly be found in our case study. Namely, an important conclusion from our case study is that the collateral capacity was more important than the time from stroke onset to successful flow restoration. It is well known that good collateral circulation in acute stroke patients is associated with better clinical and functional out- comes.11 The results of the DAWN trial show that thrombectomy plus standard care compared to standard care alone, even 6 to 24 hours after acute ischaemic stroke, yields better functional improve- ments in people with mismatch between clinical deficit and infarction.12 It is becoming obvious that the presence of the collateral flow, which defines the minimal blood flow in the penumbra, is equally important as the time in stroke patients being as- sessed for IVT.13 The clinical outcome in our patient with bilateral stroke during the same thrombolytic time window therefore confirms the importance of collaterals. Namely, the region within the brain with good collateral circulation showed a complete recovery after mechanical recanalization at 7 hours after stroke onset, while the other (contralateral) re- gion without collateral circulation exhibited a poor outcome no more than 3 hours after stroke onset. Our case shows that even in the same individual, the presence of collateral circulation varies across regions. Namely, the affected brain territory, even with comparable anatomic vascular architecture (patent ACA with possible collateral inflow) as the contralateral territory, exhibited shorter time from onset of occlusion to recanalization (with distal thrombus migration) but did not exhibit collater- als, leading to an immediate and irreversible inju- FIGURE 3. (A) Digital subtraction angiography (DSA) at the beginning of mechanical recanalization. Right internal carotid contrast injection confirming right M1 occlusion. (B) DSA at the beginning of mechanical recanalization. Left side contrast injection showing complete spontaneous recanalization of the carotid “T” occlusion with thrombembolar distal migration (occlusion of the proximal M2 segment of the major MCA branch) (arrow). A B FIGURE 4. (A) Digital subtraction angiography (DSA) after mechanical recanalization. Right M1 mechanical recanalization (aspiration device) led to complete flow restoration. (B) MR diffusion weighted imaging (DWI) scan taken 6 days after mechanical recanalization: complete salvage of the affected right middle cerebral artery (MCA) brain parenchyma (recanalization at 7 hours after stroke onset). In contrast, subsequent persistent left M2 occlusion without collateral flow resulted in significant stroke within 3 hours after stroke onset. A B Radiol Oncol 2020; 54(2): 144-148. Jeromel M et.al. / Acute bilateral cerebral artery occlusion148 ry. To the best of our knowledge, we presented the first case of subsequent contralateral large cerebral artery (MCA-ICA/MCA) occlusion during IVT, where the outcome after standard care and me- chanical thrombectomy was not dependent on the time from stroke onset but rather on the capacity of collateral circulation exclusively. Simultaneous thrombectomy, as described by Larrew et al.8, offers an efficient and feasible means to reduce the time to recanalization. However, our case study confirms the fact that the outcome is still very much dependent on the capacity of collateral circulation. The main drawback of simultaneous thrombectomy (compared to subsequent thrombec- tomy) is that it requires two neurointerventionalists and technicians (nurses). The procedure is techni- cally challenging, and the team must be methodical and organized and communicate effectively to al- low effective, efficient, simultaneous and safe pro- gression on both sides.10 It is likely that simultane- ous thrombectomy would not have any impact on the outcome in our case study of a patient with poor collaterals. Interestingly, the TICI scores for the pa- tient in our study were the same as those reported for patients treated with simultaneous thrombecto- my in previous study (TICI 3 for one side and TICI 2b for contralateral side). The presence of collat- eral capacity, the location of the residual occlusion (MCA vs ACA-MCA), and a concomitant disease (better cardiac function) were key determinants of better outcomes in the patient in our study. Understanding the importance of collaterals and preprocedural imaging with techniques that enable collateral flow assessment is becoming ex- tremely important. Multiphase CT angiography (CTA), which enables the evaluation of collateral circulation within a single contrast injection, is a simple example.14 It is already accepted that for good outcomes, the onset-to-reperfusion time win- dow should be adjusted according to the collateral status.15 In the future, perhaps a pretreatment im- aging assessment of the thrombus itself will make stroke treatment planning easier.16 However, it seems that even in the era of mechanical recanali- zation, bilateral stroke is a severe condition with unpredicted outcomes. Conclusions Acute bilateral cerebral (ICA and/or MCA) occlu- sion leads to sudden severe neurological deficits (comas) with unpredicted prognoses, even in the era of mechanical recanalization. As a the collateral capacity seems to be more important than the absolute time to flow restora- tion in determining the outcomes, simultaneous thrombectomy by itself probably does not lead to improved functional outcomes. 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