Microcatheter “First-Pass Effect” Predicts Acute Intracranial Artery Atherosclerotic Disease-Related Occlusion

Microcatheter “First-Pass Effect” Predicts Acute Intracranial Artery Atherosclerotic... Abstract BACKGROUND The differentiation between intracranial atherosclerotic stenosis (ICAS) and intracranial embolism as the immediate cause of acute ischemic stroke requiring endovascular therapy is important but challenging. In cases of ICAS, we often observe a phenomenon we call the microcatheter “first-pass effect,” which is temporary blood flow through the occluded intracranial artery when the angiographic microcatheter is initially advanced through the site of total occlusion and immediately retrieved proximally. OBJECTIVE To evaluate whether this microcatheter first-pass effect can be used to differentiate ICAS from intracranial embolism. METHODS A total of 61 patients with acute ischemic stroke resulting from large intracranial artery occlusion and in whom recanalization was achieved by endovascular treatment were included in the study. The microcatheter first-pass effect was tested in these patients. The sensitivity, specificity, positive predictive values (PPV), and accuracy of the microcatheter first-pass effect for prediction of ICAS were assessed. RESULTS The microcatheter first-pass effect was more frequently observed in patients with ICAS than in those with intracranial embolism (90.9% vs 12.8%, P < .001). For identifying ICAS, sensitivity, specificity, PPV, and accuracy of the microcatheter first-pass effect were 90.9%, 87.2%, 80.0%, 88.5%, respectively. CONCLUSION The sensitivity and PPV of the microcatheter first-pass effect are high for prediction of ICAS in patients with acute symptoms. Acute ischemic stroke, Intracranial atherosclerotic stenosis, Intracranial embolism, Endovascular therapy, Sensitivity ABBREVIATIONS ABBREVIATIONS ACG American Society of Interventional and Therapeutic Neuroradiology collateral grading scale BA basilar artery CTA computed tomography angiography HAS hyperdense artery sign ICA internal carotid artery ICAS Intracranial atherosclerotic stenosis MCA middle cerebral artery MR magnetic resonance MRA magnetic resonance angiography mRS modified Rankin Scale NIHSS NIH Stroke Scale NPV negative predictive value PPV positive predictive value TICI thrombolysis in cerebral infarction Intracranial atherosclerosis is common in Asia, and it accounts for 25% to 50% of ischemic strokes.1,2 The reported incidence of acute occlusion resulting from intracranial atherosclerotic stenosis (ICAS) is 22.9% in Asia3 and 5.5% in western countries.4 Mechanical thrombectomy is an effective treatment for acute ischemic stroke caused by intracranial artery occlusion,5-10 but it was designed primarily for embolic occlusion rather than ICAS.11 Although mechanical thrombectomy results in reperfusion, reocclusion often occurs at the site of the ICAS due to subsequent platelet aggregation.12,13 Thus, rescue therapy such as emergency angioplasty or stenting3,13,14 is often required. For these reasons, it is very important to differentiate ICAS from intracranial embolism. ICAS can be detected and evaluated by means of high-resolution vessel wall magnetic resonance (MR) imaging.15-19 However, such imaging must be performed on a 3.0T or 7.0T MR scanner, neither of which is housed by most municipal hospitals. In addition, the MR studies are time-consuming and require the patient's cooperation. Being able to differentiate ICAS from intracranial embolism during endovascular intervention would be a practical and time-saving solution to the problem. Endovascular intervention has become standard treatment for acute occlusion of a large intracranial artery, with more and more patients receiving such therapy. We have observed, especially in cases of ICAS, a phenomenon we refer to as the microcatheter “first-pass effect.” We found that blood flows slowly and temporarily through the vessel lumen at the site of occlusion when the angiographic microcatheter is advanced through the area of total occlusion and then retrieved on the proximal side of the occlusion. Thus, we conducted a retrospective study to evaluate whether the microcatheter first-pass effect observed during digital subtraction angiography can be used to differentiate ICAS from intracranial embolism. METHODS Study Patients The study included 61 patients who were identified from our registry database of consecutive acute stroke patients treated with endovascular therapy between January 2015 and mid-October 2016. The selected patients met the following criteria: (1) the ischemic stroke resulted from occlusion of a large intracranial artery; (2) the time between symptom onset and admission was 8 h or less in the case of acute anterior circulation infarct or 24 h or less in the case of acute posterior circulation infarct, or the time between symptom onset and admission was beyond the 8 or 24 h, but endovascular therapy was to be performed for a moderate-to-large hypoperfusion area as depicted by multimodal MR imaging; (3) endovascular reperfusion therapy was performed, and successful recanalization was confirmed; (4) the age was above 18 yr; and (5) the prestroke modified Rankin Scale (mRS) score was 0 to 1. Patients were excluded from the study if (1) the stroke was the result of dissection, moyamoya disease, or vasculitis; (2) the stroke was the result of tandem occlusion; or (3) the specific cause of the intracranial large artery occlusion was not determined. Our access to patients’ records for data collection and analysis of the data were approved by our local medical ethics committee. All patients provided informed consent for their clinical data to be used anonymously for research purposes. Operational Definitions of ICAS and Embolic Occlusion ICAS was differentiated from intracranial embolism collaboratively based on angiographic findings. ICAS was defined as a significant fixed focal stenosis at the site of occlusion evidenced by final angiography or during endovascular treatment.11 In addition, the stenosis could be resolved by means of angioplasty or stent insertion. Significant stenosis was defined as (1) fixed stenosis ≥70% or (2) fixed stenosis ≥50% in addition to either angiographically evident impaired perfusion or evidence of re-occlusion following sufficient treatment with a stent retriever. The underlying disorder was classified as embolism based on the following: (1) there was no evidence of focal stenosis after clot retrieval; (2) an embolus was removed with a stent retriever; and (3) MR angiography (MRA) or computed tomography angiography (CTA) performed within 1 wk after the procedure showed the responsible artery to be patent without any stenosis. Definition of the Microcatheter First-Pass Effect A schematic diagram of the first-pass effect is shown in Figure 1. When acute occlusion of a large intracranial artery is seen angiographically (Figure 1A), the following procedure is performed before thrombectomy. A microcatheter and a microwire are navigated through the area of total occlusion to the distal patent artery (Figure 1B). The microcatheter is then retrieved on the proximal side of the thrombus. Angiography is performed with a guiding catheter or microcatheter to determine whether blood flows through the vessel at the site of occlusion. Such flow is recorded as the microcatheter first-pass effect (Figure 1C). If there is no such flow, absence of the first-pass effect is noted (Figure 1D). The first-pass effect is confirmed by 2 experienced neuro-interventionists who are present during the procedure. FIGURE 1. View largeDownload slide Schematic diagram of the first-pass effect. A, Left middle cerebral artery is occluded by a thrombus. B, The angiographic microcatheter is navigated through the thrombus over a microwire. C and D, The microcatheter is retrieved with the microwire remaining in place. C Slow blood flow in the distal artery beyond the thrombus is the so-called first-pass effect. D, The absence of blood flow is absence of the first-pass effect. FIGURE 1. View largeDownload slide Schematic diagram of the first-pass effect. A, Left middle cerebral artery is occluded by a thrombus. B, The angiographic microcatheter is navigated through the thrombus over a microwire. C and D, The microcatheter is retrieved with the microwire remaining in place. C Slow blood flow in the distal artery beyond the thrombus is the so-called first-pass effect. D, The absence of blood flow is absence of the first-pass effect. Clinical and Radiological Assessment We assessed neurological function of all study patients upon admission by means of the NIH Stroke Scale (NIHSS). We then assessed patients radiologically based on the Thrombolysis in Cerebral Infarction (TICI) scale, American Society of Interventional and Therapeutic Neuroradiology collateral grading (ACG) system, and the site of occlusion, as shown in Table 1. Successful reperfusion was defined as a TICI grade of 2b or 3 after endovascular treatment, and good preprocedural collateral flow was defined as an ACG score ≥3.20 High-resolution MR imaging was performed in some patients with ICAS who did not undergo stenting. TABLE 1. Radiological Assessment Items and Their Definitions Item Definition mTICI grade • Grade 0 No perfusion • Grade 1 Antegrade reperfusion past the initial occlusion, but limited distal branch filling with little or slow distal reperfusion • Grade 2a Antegrade reperfusion of less than half of the occluded target artery previously ischemic territory • Grade 2b Antegrade reperfusion of more than half of the previously occluded target artery ischemic territory • Grade 3 Complete antegrade reperfusion of the previously occluded target artery ischemic territory, with absence of visualized occlusion in all distal branches ACG grade • Grade 0 No collaterals visible to the ischemic site • Grade 1 Slow collaterals to the periphery of the ischemic site, with persistence of some of the defect • Grade 2 Rapid collaterals to the periphery of the ischemic site, with persistence of the defect, and only to a portion of the ischemic territory • Grade 3 Collaterals with slow but complete angiographic blood flow of the ischemic bed by the late venous phase • Grade 4 Complete and rapid collateral blood flow to the vascular bed in the entire ischemic territory by retrograde perfusion Intracranial ICA occlusion • Carotid T if the terminal ICA, M1, and A1 are occluded • Carotid L if both the terminal ICA and M1 are occluded (A1 is spared) • Carotid I if only the terminal ICA is occluded (M1 and A1 are spared) MCA segment clot location • The M1 segment is taken as the first portion of the MCA to the major bifurcation • Clot is localized to the proximal or distal M1 segment according to which half of the segment is involved and whether the lenticulostriates are involved (proximal) or spared (distal) Item Definition mTICI grade • Grade 0 No perfusion • Grade 1 Antegrade reperfusion past the initial occlusion, but limited distal branch filling with little or slow distal reperfusion • Grade 2a Antegrade reperfusion of less than half of the occluded target artery previously ischemic territory • Grade 2b Antegrade reperfusion of more than half of the previously occluded target artery ischemic territory • Grade 3 Complete antegrade reperfusion of the previously occluded target artery ischemic territory, with absence of visualized occlusion in all distal branches ACG grade • Grade 0 No collaterals visible to the ischemic site • Grade 1 Slow collaterals to the periphery of the ischemic site, with persistence of some of the defect • Grade 2 Rapid collaterals to the periphery of the ischemic site, with persistence of the defect, and only to a portion of the ischemic territory • Grade 3 Collaterals with slow but complete angiographic blood flow of the ischemic bed by the late venous phase • Grade 4 Complete and rapid collateral blood flow to the vascular bed in the entire ischemic territory by retrograde perfusion Intracranial ICA occlusion • Carotid T if the terminal ICA, M1, and A1 are occluded • Carotid L if both the terminal ICA and M1 are occluded (A1 is spared) • Carotid I if only the terminal ICA is occluded (M1 and A1 are spared) MCA segment clot location • The M1 segment is taken as the first portion of the MCA to the major bifurcation • Clot is localized to the proximal or distal M1 segment according to which half of the segment is involved and whether the lenticulostriates are involved (proximal) or spared (distal) mTICI, modified Treatment in Cerebral Ischaemia score; ACG, American Society of Interventional and Therapeutic Neuroradiology Collateral grading system; ICA, internal carotid artery; MCA, middle cerebral artery. View Large TABLE 1. Radiological Assessment Items and Their Definitions Item Definition mTICI grade • Grade 0 No perfusion • Grade 1 Antegrade reperfusion past the initial occlusion, but limited distal branch filling with little or slow distal reperfusion • Grade 2a Antegrade reperfusion of less than half of the occluded target artery previously ischemic territory • Grade 2b Antegrade reperfusion of more than half of the previously occluded target artery ischemic territory • Grade 3 Complete antegrade reperfusion of the previously occluded target artery ischemic territory, with absence of visualized occlusion in all distal branches ACG grade • Grade 0 No collaterals visible to the ischemic site • Grade 1 Slow collaterals to the periphery of the ischemic site, with persistence of some of the defect • Grade 2 Rapid collaterals to the periphery of the ischemic site, with persistence of the defect, and only to a portion of the ischemic territory • Grade 3 Collaterals with slow but complete angiographic blood flow of the ischemic bed by the late venous phase • Grade 4 Complete and rapid collateral blood flow to the vascular bed in the entire ischemic territory by retrograde perfusion Intracranial ICA occlusion • Carotid T if the terminal ICA, M1, and A1 are occluded • Carotid L if both the terminal ICA and M1 are occluded (A1 is spared) • Carotid I if only the terminal ICA is occluded (M1 and A1 are spared) MCA segment clot location • The M1 segment is taken as the first portion of the MCA to the major bifurcation • Clot is localized to the proximal or distal M1 segment according to which half of the segment is involved and whether the lenticulostriates are involved (proximal) or spared (distal) Item Definition mTICI grade • Grade 0 No perfusion • Grade 1 Antegrade reperfusion past the initial occlusion, but limited distal branch filling with little or slow distal reperfusion • Grade 2a Antegrade reperfusion of less than half of the occluded target artery previously ischemic territory • Grade 2b Antegrade reperfusion of more than half of the previously occluded target artery ischemic territory • Grade 3 Complete antegrade reperfusion of the previously occluded target artery ischemic territory, with absence of visualized occlusion in all distal branches ACG grade • Grade 0 No collaterals visible to the ischemic site • Grade 1 Slow collaterals to the periphery of the ischemic site, with persistence of some of the defect • Grade 2 Rapid collaterals to the periphery of the ischemic site, with persistence of the defect, and only to a portion of the ischemic territory • Grade 3 Collaterals with slow but complete angiographic blood flow of the ischemic bed by the late venous phase • Grade 4 Complete and rapid collateral blood flow to the vascular bed in the entire ischemic territory by retrograde perfusion Intracranial ICA occlusion • Carotid T if the terminal ICA, M1, and A1 are occluded • Carotid L if both the terminal ICA and M1 are occluded (A1 is spared) • Carotid I if only the terminal ICA is occluded (M1 and A1 are spared) MCA segment clot location • The M1 segment is taken as the first portion of the MCA to the major bifurcation • Clot is localized to the proximal or distal M1 segment according to which half of the segment is involved and whether the lenticulostriates are involved (proximal) or spared (distal) mTICI, modified Treatment in Cerebral Ischaemia score; ACG, American Society of Interventional and Therapeutic Neuroradiology Collateral grading system; ICA, internal carotid artery; MCA, middle cerebral artery. View Large Patients’ clinical characteristics, risk factors for arteriosclerosis, heart disease, preoperational intravenous thrombolysis, prior stroke, the hyperdense artery sign (HAS) on non-enhanced CT, the NIHSS score upon admission, and angiographic information were recorded. Two neurologists, blinded to the patient information and study protocol, independently studied all images retrospectively. Discrepancies between the reviewers were resolved by consensus. Statistical Analysis Differences in clinical characteristics, risk factors, and imaging features between patients in whom the microcatheter first-pass effect was observed and those in whom it was not observed were examined by bivariate analysis. Differences in clinical characteristics, risk factors, imaging features, and treatment strategies between patients with ICAS and those with intracranial embolism were also examined by bivariate analysis. Student's t-test or the Mann–Whitney U-test was applied to continuous variables, and the χ2 test was applied to categorical variables. Measures of diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of the microcatheter first-pass effect for the prediction of ICAS, were calculated. All statistical analyses were performed with IBM SPSS Statistics 22.0 (IBM Inc, Armonk, New York), and P ≤ .05 was considered significant. RESULTS Patients in Whom the Microcatheter First-Pass Effect was Observed vs Patients in Whom it was not Observed The microcatheter first-pass effect was observed in 25 (41.0%) of the 61 study patients (Figure 2). Clinical characteristics are shown for patients in the first-pass effect group vs patients in the non-first-pass effect group in Table 2. Patients in the first-pass effect group, in comparison to those in the non-first-pass effect group (Figure 3), were more likely to be male (76.0% vs 47.2%, P = .025), more likely to have hypertension (80.0% vs 44.4%, P = .005), less likely to have atrial fibrillation and/or rheumatoid heart disease (12.0% vs 77.8%, P < .001), less likely to show the HAS on non-enhanced CT (21.6% vs 78.8%, P < .001), and less likely to have carotid T occlusion (0% vs 33.3%, P = .004). The collateral flow was better in the microcatheter first-pass effect group than in the non-first-pass effect group (ACG ≥ 3, 50.0% vs 18.8%, P = .015). FIGURE 2. View largeDownload slide Illustrative cases of the microcatheter first-pass effect. A 52-yr-old male smoker presented with right hemiparesis and aphasia. A, DSA revealed total occlusion of the terminal segment of the left ICA (black arrow). B, The microcatheter first-pass effect without focal stenosis was observed (black arrow indicates the distal end of the proximally retrieved the retrieved microcatheter). C, A 6.0-mm × 30-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through the site. D, Severe stenosis was seen after a single pass of the stent retriever (black arrow). E, Postoperative MRA showed severe stenosis of the terminal segment of the left ICA (black arrow), and the high-solution MR (TIWI) image at the bottom right shows an irregular plaque within the terminal segment of the left ICA (white arrowhead). A 78-yr-old male smoker presented with left hemiparesis. F, DSA revealed total occlusion of the right distal MCA (black arrow). G, The microcatheter first-pass effect without focal stenosis was observed. Slow blood flow was seen (black arrow) when the microcatheter was retrieved back to the proximal to the thrombus. H, A 4.0-mm × 20-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through the site. I, TICI grade 3 recanalization was achieved after a single pass of the stent retriever. J, Postoperative MRA confirmed the patency of the right MCA. DSA indicates digital subtraction angiography; ICA, internal carotid artery; MCA, middle cerebral artery. FIGURE 2. View largeDownload slide Illustrative cases of the microcatheter first-pass effect. A 52-yr-old male smoker presented with right hemiparesis and aphasia. A, DSA revealed total occlusion of the terminal segment of the left ICA (black arrow). B, The microcatheter first-pass effect without focal stenosis was observed (black arrow indicates the distal end of the proximally retrieved the retrieved microcatheter). C, A 6.0-mm × 30-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through the site. D, Severe stenosis was seen after a single pass of the stent retriever (black arrow). E, Postoperative MRA showed severe stenosis of the terminal segment of the left ICA (black arrow), and the high-solution MR (TIWI) image at the bottom right shows an irregular plaque within the terminal segment of the left ICA (white arrowhead). A 78-yr-old male smoker presented with left hemiparesis. F, DSA revealed total occlusion of the right distal MCA (black arrow). G, The microcatheter first-pass effect without focal stenosis was observed. Slow blood flow was seen (black arrow) when the microcatheter was retrieved back to the proximal to the thrombus. H, A 4.0-mm × 20-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through the site. I, TICI grade 3 recanalization was achieved after a single pass of the stent retriever. J, Postoperative MRA confirmed the patency of the right MCA. DSA indicates digital subtraction angiography; ICA, internal carotid artery; MCA, middle cerebral artery. FIGURE 2. View largeDownload slide Illustrative cases of the microcatheter first-pass effect. A 52-yr-old male smoker presented with right hemiparesis and aphasia. A, DSA revealed total occlusion of the terminal segment of the left ICA (black arrow). B, The microcatheter first-pass effect without focal stenosis was observed (black arrow indicates the distal end of the proximally retrieved the retrieved microcatheter). C, A 6.0-mm × 30-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through the site. D, Severe stenosis was seen after a single pass of the stent retriever (black arrow). E, Postoperative MRA showed severe stenosis of the terminal segment of the left ICA (black arrow), and the high-solution MR (TIWI) image at the bottom right shows an irregular plaque within the terminal segment of the left ICA (white arrowhead). A 78-yr-old male smoker presented with left hemiparesis. F, DSA revealed total occlusion of the right distal MCA (black arrow). G, The microcatheter first-pass effect without focal stenosis was observed. Slow blood flow was seen (black arrow) when the microcatheter was retrieved back to the proximal to the thrombus. H, A 4.0-mm × 20-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through the site. I, TICI grade 3 recanalization was achieved after a single pass of the stent retriever. J, Postoperative MRA confirmed the patency of the right MCA. DSA indicates digital subtraction angiography; ICA, internal carotid artery; MCA, middle cerebral artery. FIGURE 2. View largeDownload slide Illustrative cases of the microcatheter first-pass effect. A 52-yr-old male smoker presented with right hemiparesis and aphasia. A, DSA revealed total occlusion of the terminal segment of the left ICA (black arrow). B, The microcatheter first-pass effect without focal stenosis was observed (black arrow indicates the distal end of the proximally retrieved the retrieved microcatheter). C, A 6.0-mm × 30-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through the site. D, Severe stenosis was seen after a single pass of the stent retriever (black arrow). E, Postoperative MRA showed severe stenosis of the terminal segment of the left ICA (black arrow), and the high-solution MR (TIWI) image at the bottom right shows an irregular plaque within the terminal segment of the left ICA (white arrowhead). A 78-yr-old male smoker presented with left hemiparesis. F, DSA revealed total occlusion of the right distal MCA (black arrow). G, The microcatheter first-pass effect without focal stenosis was observed. Slow blood flow was seen (black arrow) when the microcatheter was retrieved back to the proximal to the thrombus. H, A 4.0-mm × 20-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through the site. I, TICI grade 3 recanalization was achieved after a single pass of the stent retriever. J, Postoperative MRA confirmed the patency of the right MCA. DSA indicates digital subtraction angiography; ICA, internal carotid artery; MCA, middle cerebral artery. TABLE 2. Clinical Characteristics of Patients in Whom the Microcatheter First-Pass Effect was Seen and Patients in Whom it was not Seen First-pass Effect (n = 25) No First-pass Effect (n = 36) P value Sex (male, n) 19 (76.0%) 17 (47.2%) .025 Age (mean, years) 62 ± 11 64 ± 9 .522 Smoker 16(64.0%) 16 (44.4%) .133 Hypertension n (%) 18 (80.0%) 16(44.4%) .005 Diabetes mellitus, n (%) 4 (16.0%) 4(11.1%) .864 Hyperlipidemia, n (%) 4(16.0%) 3(8.3%) .606 Atrial fibrillation and/or rheumatic heart disease 3 (12.0%) 28 (77.8%) <.001 Transient ischemic attack 2(8.0%) 0 (0%) .056 Admission NHISS 15.9 ± 6 18.2 ± 5 .110 Intravenous thrombolysis, n (%) 8 (32.0%) 9 (25.0%) .549 HAS on CT, n (%)a 6 (21.6%) 26 (78.8%) <.001 Occlusion classification/site, n (%)  ICA terminus   Carotid T 0 (0%) 12 (33.3%) .004   Carotid L 2 (8.0%) 2 (5.6%) 1.000   Isolated intracranial ICA 4(16.0%) 3 (8.3%) .606  MCA   M1 segment-proximal 11 (44.0%) 11 (25.0%) .120   M1 segment-distal 5 (20.0%) 7 (19.4%) 1.000  BA 3 (12.0%) 4 (11.1%) 1.000 Good collateral flow,b n (%) .015  ACG ≥ 3 11/22(50.0%) 6/32(18.8%) First-pass Effect (n = 25) No First-pass Effect (n = 36) P value Sex (male, n) 19 (76.0%) 17 (47.2%) .025 Age (mean, years) 62 ± 11 64 ± 9 .522 Smoker 16(64.0%) 16 (44.4%) .133 Hypertension n (%) 18 (80.0%) 16(44.4%) .005 Diabetes mellitus, n (%) 4 (16.0%) 4(11.1%) .864 Hyperlipidemia, n (%) 4(16.0%) 3(8.3%) .606 Atrial fibrillation and/or rheumatic heart disease 3 (12.0%) 28 (77.8%) <.001 Transient ischemic attack 2(8.0%) 0 (0%) .056 Admission NHISS 15.9 ± 6 18.2 ± 5 .110 Intravenous thrombolysis, n (%) 8 (32.0%) 9 (25.0%) .549 HAS on CT, n (%)a 6 (21.6%) 26 (78.8%) <.001 Occlusion classification/site, n (%)  ICA terminus   Carotid T 0 (0%) 12 (33.3%) .004   Carotid L 2 (8.0%) 2 (5.6%) 1.000   Isolated intracranial ICA 4(16.0%) 3 (8.3%) .606  MCA   M1 segment-proximal 11 (44.0%) 11 (25.0%) .120   M1 segment-distal 5 (20.0%) 7 (19.4%) 1.000  BA 3 (12.0%) 4 (11.1%) 1.000 Good collateral flow,b n (%) .015  ACG ≥ 3 11/22(50.0%) 6/32(18.8%) aPlain CT not done for 5 patients. bIn the anterior circulation. NHISS indicates NIH stroke scale; HAS, hyper-dense artery signs; ICA, internal carotid artery; MCA, middle cerebral artery; BA, basilar artery; ACG, American Society of Interventional and Therapeutic Neuroradiology collateral grading system. View Large TABLE 2. Clinical Characteristics of Patients in Whom the Microcatheter First-Pass Effect was Seen and Patients in Whom it was not Seen First-pass Effect (n = 25) No First-pass Effect (n = 36) P value Sex (male, n) 19 (76.0%) 17 (47.2%) .025 Age (mean, years) 62 ± 11 64 ± 9 .522 Smoker 16(64.0%) 16 (44.4%) .133 Hypertension n (%) 18 (80.0%) 16(44.4%) .005 Diabetes mellitus, n (%) 4 (16.0%) 4(11.1%) .864 Hyperlipidemia, n (%) 4(16.0%) 3(8.3%) .606 Atrial fibrillation and/or rheumatic heart disease 3 (12.0%) 28 (77.8%) <.001 Transient ischemic attack 2(8.0%) 0 (0%) .056 Admission NHISS 15.9 ± 6 18.2 ± 5 .110 Intravenous thrombolysis, n (%) 8 (32.0%) 9 (25.0%) .549 HAS on CT, n (%)a 6 (21.6%) 26 (78.8%) <.001 Occlusion classification/site, n (%)  ICA terminus   Carotid T 0 (0%) 12 (33.3%) .004   Carotid L 2 (8.0%) 2 (5.6%) 1.000   Isolated intracranial ICA 4(16.0%) 3 (8.3%) .606  MCA   M1 segment-proximal 11 (44.0%) 11 (25.0%) .120   M1 segment-distal 5 (20.0%) 7 (19.4%) 1.000  BA 3 (12.0%) 4 (11.1%) 1.000 Good collateral flow,b n (%) .015  ACG ≥ 3 11/22(50.0%) 6/32(18.8%) First-pass Effect (n = 25) No First-pass Effect (n = 36) P value Sex (male, n) 19 (76.0%) 17 (47.2%) .025 Age (mean, years) 62 ± 11 64 ± 9 .522 Smoker 16(64.0%) 16 (44.4%) .133 Hypertension n (%) 18 (80.0%) 16(44.4%) .005 Diabetes mellitus, n (%) 4 (16.0%) 4(11.1%) .864 Hyperlipidemia, n (%) 4(16.0%) 3(8.3%) .606 Atrial fibrillation and/or rheumatic heart disease 3 (12.0%) 28 (77.8%) <.001 Transient ischemic attack 2(8.0%) 0 (0%) .056 Admission NHISS 15.9 ± 6 18.2 ± 5 .110 Intravenous thrombolysis, n (%) 8 (32.0%) 9 (25.0%) .549 HAS on CT, n (%)a 6 (21.6%) 26 (78.8%) <.001 Occlusion classification/site, n (%)  ICA terminus   Carotid T 0 (0%) 12 (33.3%) .004   Carotid L 2 (8.0%) 2 (5.6%) 1.000   Isolated intracranial ICA 4(16.0%) 3 (8.3%) .606  MCA   M1 segment-proximal 11 (44.0%) 11 (25.0%) .120   M1 segment-distal 5 (20.0%) 7 (19.4%) 1.000  BA 3 (12.0%) 4 (11.1%) 1.000 Good collateral flow,b n (%) .015  ACG ≥ 3 11/22(50.0%) 6/32(18.8%) aPlain CT not done for 5 patients. bIn the anterior circulation. NHISS indicates NIH stroke scale; HAS, hyper-dense artery signs; ICA, internal carotid artery; MCA, middle cerebral artery; BA, basilar artery; ACG, American Society of Interventional and Therapeutic Neuroradiology collateral grading system. View Large FIGURE 3. View largeDownload slide Illustrative cases of the absence of the microcatheter first-pass effect. A 71-yr-old man presented with quadriplegia and drowsiness. A, DSA showed total occlusion of the proximal BA (black arrow). B, The microcatheter first-pass effect was not seen (black arrow indicates the distal end of the retrieved microcatheter). C, An angiogram obtained when the stent retriever was unsheathed at the second time revealed a high clot burden (black arrow). D, 60% stenosis was observed at the site of proximal BA occlusion after 2 passes of the stent retriever followed by emergency angioplasty performed with a 2.5-mm × 9-mm Gateway balloon. E, Postoperative MRA revealed severe BA stenosis. A 59-yr-old man presented with left hemiparesis. F, DSA showed total occlusion of the right proximal MCA (black arrow). G, The microcatheter first-pass effect was not seen (black arrow indicates the distal end of the retrieved microcatheter). H, A 4.0-mm × 20-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through. I, TICI grade 3 recanalization was achieved after a single pass of the stent retriever. J, Postoperative MRA showed the right MCA to be patent. DSA indicates digital subtraction angiography, BA, basilar artery, MCA, middle cerebral artery. FIGURE 3. View largeDownload slide Illustrative cases of the absence of the microcatheter first-pass effect. A 71-yr-old man presented with quadriplegia and drowsiness. A, DSA showed total occlusion of the proximal BA (black arrow). B, The microcatheter first-pass effect was not seen (black arrow indicates the distal end of the retrieved microcatheter). C, An angiogram obtained when the stent retriever was unsheathed at the second time revealed a high clot burden (black arrow). D, 60% stenosis was observed at the site of proximal BA occlusion after 2 passes of the stent retriever followed by emergency angioplasty performed with a 2.5-mm × 9-mm Gateway balloon. E, Postoperative MRA revealed severe BA stenosis. A 59-yr-old man presented with left hemiparesis. F, DSA showed total occlusion of the right proximal MCA (black arrow). G, The microcatheter first-pass effect was not seen (black arrow indicates the distal end of the retrieved microcatheter). H, A 4.0-mm × 20-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through. I, TICI grade 3 recanalization was achieved after a single pass of the stent retriever. J, Postoperative MRA showed the right MCA to be patent. DSA indicates digital subtraction angiography, BA, basilar artery, MCA, middle cerebral artery. FIGURE 3. View largeDownload slide Illustrative cases of the absence of the microcatheter first-pass effect. A 71-yr-old man presented with quadriplegia and drowsiness. A, DSA showed total occlusion of the proximal BA (black arrow). B, The microcatheter first-pass effect was not seen (black arrow indicates the distal end of the retrieved microcatheter). C, An angiogram obtained when the stent retriever was unsheathed at the second time revealed a high clot burden (black arrow). D, 60% stenosis was observed at the site of proximal BA occlusion after 2 passes of the stent retriever followed by emergency angioplasty performed with a 2.5-mm × 9-mm Gateway balloon. E, Postoperative MRA revealed severe BA stenosis. A 59-yr-old man presented with left hemiparesis. F, DSA showed total occlusion of the right proximal MCA (black arrow). G, The microcatheter first-pass effect was not seen (black arrow indicates the distal end of the retrieved microcatheter). H, A 4.0-mm × 20-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through. I, TICI grade 3 recanalization was achieved after a single pass of the stent retriever. J, Postoperative MRA showed the right MCA to be patent. DSA indicates digital subtraction angiography, BA, basilar artery, MCA, middle cerebral artery. FIGURE 3. View largeDownload slide Illustrative cases of the absence of the microcatheter first-pass effect. A 71-yr-old man presented with quadriplegia and drowsiness. A, DSA showed total occlusion of the proximal BA (black arrow). B, The microcatheter first-pass effect was not seen (black arrow indicates the distal end of the retrieved microcatheter). C, An angiogram obtained when the stent retriever was unsheathed at the second time revealed a high clot burden (black arrow). D, 60% stenosis was observed at the site of proximal BA occlusion after 2 passes of the stent retriever followed by emergency angioplasty performed with a 2.5-mm × 9-mm Gateway balloon. E, Postoperative MRA revealed severe BA stenosis. A 59-yr-old man presented with left hemiparesis. F, DSA showed total occlusion of the right proximal MCA (black arrow). G, The microcatheter first-pass effect was not seen (black arrow indicates the distal end of the retrieved microcatheter). H, A 4.0-mm × 20-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through. I, TICI grade 3 recanalization was achieved after a single pass of the stent retriever. J, Postoperative MRA showed the right MCA to be patent. DSA indicates digital subtraction angiography, BA, basilar artery, MCA, middle cerebral artery. Patients With ICAS vs Patients With Embolism ICAS was diagnosed in 22 (36.1%) of the 61 patients. The clinical characteristics are shown for patients in the ICAS group vs patients in the non-ICAS (intracranial embolism) group in Table 3. The ICAS patients were more likely to be male (81.8% vs 46.2%, P = .007), more likely to have hypertension (86.4% vs 43.6%, P = .001), more likely to have suffered a TIA (9.1% vs 0%, P = .040), less likely to have atrial fibrillation and/or rheumatoid heart disease (0% vs 79.5%, P < .001), less likely to show HAS on non-enhanced CT (22.2% vs 73.7%, P < .001), and less likely to have a carotid T occlusion (0% vs 30.8%, P = .010). The collateral flow was better in the ICAS group than in the non-ICAS group (ACG ≥ 3, 58.8% vs 18.9%, P = .003). Nineteen (86.4%) of the 22 ICAS patients required emergency angioplasty for successful recanalization (Table 4). Nine patients with ICAS who did not receive a stent underwent high-resolution MR imaging. The stenosis in these cases was located in the proximal M1 segment (n = 4), the internal carotid terminus segment (n = 3), the distal M1 segment (n = 1), or the basilar artery (BA; n = 1). Stenosis of the responsible artery was observed in time-of-flight MRA, with irregular arteriosclerotic plaques of various thicknesses observed on volume isotropic turbo spin echo acquisition images in all 9 cases. TABLE 3. Clinical Characteristics of Patients in the ICAS Group and Embolism Group ICAS group (n = 22) Embolism group (n = 39) P value Sex (male, n) 18(81.8%) 18 (46.2%) .007 Age (mean, years) 61 ± 10 65 ± 10 .114 Smoker 17 (77.3%) 15 (38.5%) .004 Hypertension, n (%) 19 (86.4%) 17 (43.6%) .001 Diabetes mellitus n (%) 3 (13.6%) 5(12.8%) 1.000 Hyperlipidemia, n (%) 5(22.7%) 2 (5.1%) .098 Atrial fibrillation and/or rheumatic heart disease 0(0%) 31(79.5%) < .001 Transient ischemic attack 2 (9.1%) 0 (0%) .040 Admission NHISS 16.9 ± 7 17.4 ± 4 .752 Intravenous thrombolysis, n (%) 4 (18.2%) 13 (33.3%) .205 HAS positive on CT n (%) a 4 (22.2%) 28 (73.7%) < .001 Occlusion classification/site, n (%)  ICA terminus   Carotid T 0 (0%) 12 (30.8%) .010   Carotid L 2 (9.1%) 2 (5.1%) .951   Isolated intracranial ICA 4 (18.2%) 3 (7.7%) .414  MCA   M1 segment-proximal 10 (45.5%) 10 (25.6%) .113   M1 segment-Distal 1(4.5%) 11 (28.2%) .058  BA 5 (22.7%) 2 (5.1%) .098 Good collateral flowb, n (%)a .003  ACG ≥ 3 10/17 (58.8%) 7/37 (18.9%) Microcatheter first pass ‘‘effect’’ 20 (90.9%) 5 (12.8%) < .001 ICAS group (n = 22) Embolism group (n = 39) P value Sex (male, n) 18(81.8%) 18 (46.2%) .007 Age (mean, years) 61 ± 10 65 ± 10 .114 Smoker 17 (77.3%) 15 (38.5%) .004 Hypertension, n (%) 19 (86.4%) 17 (43.6%) .001 Diabetes mellitus n (%) 3 (13.6%) 5(12.8%) 1.000 Hyperlipidemia, n (%) 5(22.7%) 2 (5.1%) .098 Atrial fibrillation and/or rheumatic heart disease 0(0%) 31(79.5%) < .001 Transient ischemic attack 2 (9.1%) 0 (0%) .040 Admission NHISS 16.9 ± 7 17.4 ± 4 .752 Intravenous thrombolysis, n (%) 4 (18.2%) 13 (33.3%) .205 HAS positive on CT n (%) a 4 (22.2%) 28 (73.7%) < .001 Occlusion classification/site, n (%)  ICA terminus   Carotid T 0 (0%) 12 (30.8%) .010   Carotid L 2 (9.1%) 2 (5.1%) .951   Isolated intracranial ICA 4 (18.2%) 3 (7.7%) .414  MCA   M1 segment-proximal 10 (45.5%) 10 (25.6%) .113   M1 segment-Distal 1(4.5%) 11 (28.2%) .058  BA 5 (22.7%) 2 (5.1%) .098 Good collateral flowb, n (%)a .003  ACG ≥ 3 10/17 (58.8%) 7/37 (18.9%) Microcatheter first pass ‘‘effect’’ 20 (90.9%) 5 (12.8%) < .001 aPlain CT not done for 5 patients. bIn the anterior circulation. NHISS indicates NIH stroke scale; HAS, hyper-dense artery sign; ICA, internal carotid artery; MCA, middle cerebral artery; BA, basilar artery; ACG, American Society of Interventional and Therapeutic Neuroradiology collateral grading system. View Large TABLE 3. Clinical Characteristics of Patients in the ICAS Group and Embolism Group ICAS group (n = 22) Embolism group (n = 39) P value Sex (male, n) 18(81.8%) 18 (46.2%) .007 Age (mean, years) 61 ± 10 65 ± 10 .114 Smoker 17 (77.3%) 15 (38.5%) .004 Hypertension, n (%) 19 (86.4%) 17 (43.6%) .001 Diabetes mellitus n (%) 3 (13.6%) 5(12.8%) 1.000 Hyperlipidemia, n (%) 5(22.7%) 2 (5.1%) .098 Atrial fibrillation and/or rheumatic heart disease 0(0%) 31(79.5%) < .001 Transient ischemic attack 2 (9.1%) 0 (0%) .040 Admission NHISS 16.9 ± 7 17.4 ± 4 .752 Intravenous thrombolysis, n (%) 4 (18.2%) 13 (33.3%) .205 HAS positive on CT n (%) a 4 (22.2%) 28 (73.7%) < .001 Occlusion classification/site, n (%)  ICA terminus   Carotid T 0 (0%) 12 (30.8%) .010   Carotid L 2 (9.1%) 2 (5.1%) .951   Isolated intracranial ICA 4 (18.2%) 3 (7.7%) .414  MCA   M1 segment-proximal 10 (45.5%) 10 (25.6%) .113   M1 segment-Distal 1(4.5%) 11 (28.2%) .058  BA 5 (22.7%) 2 (5.1%) .098 Good collateral flowb, n (%)a .003  ACG ≥ 3 10/17 (58.8%) 7/37 (18.9%) Microcatheter first pass ‘‘effect’’ 20 (90.9%) 5 (12.8%) < .001 ICAS group (n = 22) Embolism group (n = 39) P value Sex (male, n) 18(81.8%) 18 (46.2%) .007 Age (mean, years) 61 ± 10 65 ± 10 .114 Smoker 17 (77.3%) 15 (38.5%) .004 Hypertension, n (%) 19 (86.4%) 17 (43.6%) .001 Diabetes mellitus n (%) 3 (13.6%) 5(12.8%) 1.000 Hyperlipidemia, n (%) 5(22.7%) 2 (5.1%) .098 Atrial fibrillation and/or rheumatic heart disease 0(0%) 31(79.5%) < .001 Transient ischemic attack 2 (9.1%) 0 (0%) .040 Admission NHISS 16.9 ± 7 17.4 ± 4 .752 Intravenous thrombolysis, n (%) 4 (18.2%) 13 (33.3%) .205 HAS positive on CT n (%) a 4 (22.2%) 28 (73.7%) < .001 Occlusion classification/site, n (%)  ICA terminus   Carotid T 0 (0%) 12 (30.8%) .010   Carotid L 2 (9.1%) 2 (5.1%) .951   Isolated intracranial ICA 4 (18.2%) 3 (7.7%) .414  MCA   M1 segment-proximal 10 (45.5%) 10 (25.6%) .113   M1 segment-Distal 1(4.5%) 11 (28.2%) .058  BA 5 (22.7%) 2 (5.1%) .098 Good collateral flowb, n (%)a .003  ACG ≥ 3 10/17 (58.8%) 7/37 (18.9%) Microcatheter first pass ‘‘effect’’ 20 (90.9%) 5 (12.8%) < .001 aPlain CT not done for 5 patients. bIn the anterior circulation. NHISS indicates NIH stroke scale; HAS, hyper-dense artery sign; ICA, internal carotid artery; MCA, middle cerebral artery; BA, basilar artery; ACG, American Society of Interventional and Therapeutic Neuroradiology collateral grading system. View Large TABLE 4. Endovascular Therapy in the ICAS Group and Embolism Group ICAS group (n = 22) Embolism group (n = 39) P value Intracranial artery angioplasty  With balloon 4 (18.2%) 0 (0%) .027  With stent 3 (13.6%) 0 (0%) .080  With balloon and stent 2 (9.1%) 0 (0%) .040  Stenting after clot retrieval 5 (22.7%) 0 (0%) .009  Balloon angioplasty after clot retrieval 4 (18.2%) 0 (0%) .027  With Balloon and stent balloon plus stent 1 (4.5%) 0 (0%) .150 Mechanical thrombectomy 3 (13.6%) 39 (100%) <.001 ICAS group (n = 22) Embolism group (n = 39) P value Intracranial artery angioplasty  With balloon 4 (18.2%) 0 (0%) .027  With stent 3 (13.6%) 0 (0%) .080  With balloon and stent 2 (9.1%) 0 (0%) .040  Stenting after clot retrieval 5 (22.7%) 0 (0%) .009  Balloon angioplasty after clot retrieval 4 (18.2%) 0 (0%) .027  With Balloon and stent balloon plus stent 1 (4.5%) 0 (0%) .150 Mechanical thrombectomy 3 (13.6%) 39 (100%) <.001 View Large TABLE 4. Endovascular Therapy in the ICAS Group and Embolism Group ICAS group (n = 22) Embolism group (n = 39) P value Intracranial artery angioplasty  With balloon 4 (18.2%) 0 (0%) .027  With stent 3 (13.6%) 0 (0%) .080  With balloon and stent 2 (9.1%) 0 (0%) .040  Stenting after clot retrieval 5 (22.7%) 0 (0%) .009  Balloon angioplasty after clot retrieval 4 (18.2%) 0 (0%) .027  With Balloon and stent balloon plus stent 1 (4.5%) 0 (0%) .150 Mechanical thrombectomy 3 (13.6%) 39 (100%) <.001 ICAS group (n = 22) Embolism group (n = 39) P value Intracranial artery angioplasty  With balloon 4 (18.2%) 0 (0%) .027  With stent 3 (13.6%) 0 (0%) .080  With balloon and stent 2 (9.1%) 0 (0%) .040  Stenting after clot retrieval 5 (22.7%) 0 (0%) .009  Balloon angioplasty after clot retrieval 4 (18.2%) 0 (0%) .027  With Balloon and stent balloon plus stent 1 (4.5%) 0 (0%) .150 Mechanical thrombectomy 3 (13.6%) 39 (100%) <.001 View Large Diagnostic Performance of the Microcatheter First-Pass Effect The microcatheter first-pass effect was positive in 20 of the 22 patients in the ICAS group but in only 5 patients in the non-ICAS group (90.9% vs 12.8%, respectively, P < .001). Sensitivity of the microcatheter first-pass effect for the detection of ICAS was 90.9%, specificity was 87.2%, PPV was 80.0%, NPV was 94.4%, and accuracy was 88.5%. DISCUSSION To the best of our knowledge, ours is the first study to show that clinicians can apply what we refer to as the microcatheter first-pass effect during endovascular intervention to differentiate ICAS from intracranial embolism. The microcatheter first-pass effect is the temporary slow blood flow seen at the site of total occlusion when a microcatheter is advanced through the affected artery and then retrieved on the proximal side of the occlusion. The phenomenon itself was first mentioned by Lee et al,21 but they did not report that the interventionist can use it to differentiate ICAS from embolism. The microcatheter first-pass effect may result from the fact that the fresh clot burden is low in a stenotic intracranial artery;3 the clot may easily break loose. When the microcatheter is advanced through a totally occluded artery, a portion of the fresh thrombus may be pushed into the distal patent segment, where it dissolves, and a portion may adhere to the vessel wall. Thus, a channel is established, and when the microcatheter is retrieved proximal to the occlusion site, transient slow flow can be seen angiographically. Our study showed significant association between the microcatheter first-pass effect and ICAS (90.9% in the ICAS group vs 12.8% in the non-ICAS group, P < .001) with high sensitivity (90.9%), high specificity (87.2%), high PPV (80%), high NPV (94.4%), and high accuracy (88.5%). Five other factors associated with ICAS differed between our patients in whom the first-pass effect was observed and those in whom it was not. The first was the presence of arteriosclerotic risk factors, hypertension in particular. Hypertension has been associated with ICAS.11 The second was the prevalence of male sex, which corresponds to results of a study conducted by Lee et al11 that showed an increased likelihood of ICAS among male patients. The third was absence of atrial fibrillation and/or a history of rheumatoid heart disease. Atrial fibrillation and rheumatic heart disease are conditions that put patients at risk for cardiac-embolic stroke. The fourth factor was the low occurrence of the HAS on nonenhanced CT. HAS is related to many factors such as the thrombus volume, stroke subtype, and components of the thrombus.22,23 Red thrombi are usually generated in diseased heart and are rich in red cells, whereas white thrombi are usually generated in atherosclerotic intracranial vessels and are rich in platelets.22 The density of white thrombi is lower than that of red thrombi,24,25 so the HAS is predictive of cardioembolic stroke.22 Finally, the most supportive point was that atherosclerosis plaque was observed on high-resolution MR images in 9 of the 22 ICAS cases, and first-pass effect was observed in all 9 of these cases. We found no carotid T occlusion in either the microcatheter first-pass effect group or the ICAS group. It may be that the carotid T occlusion is related more to intracranial embolism and that the resulting thrombus burden is high.26,27 Thus, after the microcatheter is advanced through the site of occlusion and retrieved on the proximal side of the embolus, the artery is once again occluded by the high-burden thrombus, and the microcatheter first-pass effect is not observed. Half (11/22, 50%) of the ICAS-related sites of occlusion were within the MCA, and the second most common sites were the intracranial ICA (6/22, 27.3%) and BA (5/22, 22.7%). Although the optimal treatment for underlying ICAS in patients presenting with hyperacute stroke remains unknown, the identification of underlying ICAS before endovascular therapy may help interventionists make appropriate therapeutic decisions.19 Nineteen (86.4%) of our 22 study patients with ICAS required angioplasty for recanalization to be achieved, and this was done on an emergency basis. Therefore, we believe the neuro-interventionist can utilize this phenomenon to distinguish ICAS from embolism and then choose the most appropriate treatment. Platelets play an important role in rethrombosis in patients with ICAS, and antiplatelet therapy can be applied to inhibit re-occlusion.12,13 Once the microcatheter first-pass effect is observed, the probability of ICAS-related occlusion is high. We can administer tirofiban, which is a fast-acting, fast-deactivated, highly selective, non-peptide platelet membrane glycoprotein IIb/IIIa receptor inhibitor.28 It is important to note that the clots in our ICAS patients were refractory to mechanical retrieval, necessitating emergency angioplasty. After diagnosing ICAS based on the first-pass effect, we can minimize the passage of a stent retriever, which can damage the arterial wall.29 Additionally, limited passage of the stent retriever can minimize the procedure time, which factors into a good prognosis.9 Our findings must be interpreted in light of the fact that they are based on single-center study. We also note that it might be difficult to differentiate underlying stenosis from residual emboli angiographically in patients who have undergone mechanical thrombectomy. CTA or MRA performed after the endovascular procedure in our patients with embolism showed that the responsible artery was patent without stenosis, whereas high-resolution MR performed in some of the patients with ICAS showed various degrees of stenosis and arthrosclerosis plaque burden in the responsible artery. These imaging studies verified that the differentiation between ICAS and embolism in our study patients was accurate. CONCLUSION In conclusion, we found the sensitivity of the microcatheter first-pass effect to be high for the identification of ICAS. Thus, the microcatheter first-pass effect can be used in determining an appropriate treatment strategy for patients with acute stroke. Disclosure The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES 1. Wang Y , Zhao X , Liu L et al. Prevalence and outcomes of symptomatic intracranial large artery stenoses and occlusions in China: the Chinese Intracranial Atherosclerosis (CICAS) Study . Stroke . 2014 ; 45 ( 3 ): 663 - 669 . Google Scholar CrossRef Search ADS PubMed 2. Gorelick PB , Wong KS , Bae H-J , Pandey DK . Large artery intracranial occlusive disease: a large worldwide burden but a relatively neglected frontier . Stroke . 2008 ; 39 ( 8 ): 2396 - 2399 . Google Scholar CrossRef Search ADS PubMed 3. Yoon W , Kim SK , Park MS , Kim BC , Kang HK . Endovascular treatment and the outcomes of atherosclerotic intracranial stenosis in patients with hyperacute stroke . Neurosurgery . 2015 ; 76 ( 6 ): 680 - 686 . Google Scholar CrossRef Search ADS PubMed 4. Gascou G , Lobotesis K , Machi P et al. Stent retrievers in acute ischemic stroke: complications and failures during the perioperative period . AJNR Am J Neuroradiol . 2014 ; 35 ( 6 ): 734 - 740 . Google Scholar CrossRef Search ADS PubMed 5. Campbell BC V , Mitchell PJ , Kleinig TJ et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection . N Engl J Med . 2015 ; 372 ( 11 ): 1009 - 1018 . Google Scholar CrossRef Search ADS PubMed 6. Goyal M , Demchuk AM , Menon BK et al. Randomized assessment of rapid endovascular treatment of ischemic stroke . N Engl J Med . 2015 ; 372 : 1019 - 1030 . Google Scholar CrossRef Search ADS PubMed 7. Saver JL , Goyal M , Bonafe A et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke . N Engl J Med . 2015 ; 372 ( 11 ): 2285 - 2295 . Google Scholar CrossRef Search ADS PubMed 8. Jovin TG , Chamorro A , Cobo E et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke . N Engl J Med . 2015 ; 372 ( 24 ): 2296 - 2306 . Google Scholar CrossRef Search ADS PubMed 9. Berkhemer OA , Fransen PSS , Beumer D et al. A randomized trial of intraarterial treatment for acute ischemic stroke . N Engl J Med . 2015 ; 372 ( 1 ): 11 - 20 . Google Scholar CrossRef Search ADS PubMed 10. Powers WJ , Derdeyn CP , Biller J et al. American Heart Association/American Stroke Association focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: a guideline for healthcare professionals from the American Heart Association/American Stroke Association . Stroke . 2015 ; 46 ( 10 ): 3020 - 3035 . Google Scholar CrossRef Search ADS PubMed 11. Lee JS , Hong JM , Lee KS et al. Endovascular therapy of cerebral arterial occlusions: intracranial atherosclerosis vs embolism . J Stroke Cerebrovasc Dis . 2015 ; 24 ( 9 ): 2074 - 2080 . Google Scholar CrossRef Search ADS PubMed 12. Kang D-H , Kim Y-W , Hwang Y-H , Park SP , Kim YS , Baik SK . Instant reocclusion following mechanical thrombectomy of in situ thromboocclusion and the role of low-dose intra-arterial tirofiban . Cerebrovasc Dis 37 ( 5 ): 350 - 5 . doi: 10.1159/000362435 . CrossRef Search ADS PubMed 13. Heo JH , Lee KY , Kim SH , Kim DI . Immediate reocclusion following a successful thrombolysis in acute stroke: a pilot study . Neurology . 2014 ; 60 ( 10 ): 1684 - 1687 . Google Scholar CrossRef Search ADS 14. Gao F , Lo WT , Sun X , Mo DP , Ma N , Miao ZR . Combined use of mechanical thrombectomy with angioplasty and stenting for acute basilar occlusions with underlying severe intracranial vertebrobasilar stenosis: preliminary experience from a single Chinese center . AJNR Am J Neuroradiol . 2015 ; 36 ( 10 ): 1947 - 1952 . Google Scholar CrossRef Search ADS PubMed 15. Dieleman N , van der Kolk AG , Zwanenburg JJM et al. Imaging intracranial vessel wall pathology with magnetic resonance imaging: current prospects and future directions . Circulation . 2014 ; 130 ( 2 ): 192 - 201 . Google Scholar CrossRef Search ADS PubMed 16. Natori T , Sasaki M , Miyoshi M et al. Evaluating middle cerebral artery atherosclerotic lesions in acute ischemic stroke using magnetic resonance T1-weighted 3-dimensional vessel wall imaging . J Stroke Cerebrovasc Dis . 2014 ; 23 ( 4 ): 706 - 711 . Google Scholar CrossRef Search ADS PubMed 17. Park JK , Kim SH , Kim BS et al. Imaging of intracranial plaques with black-blood double inversion recovery MR imaging and CT . J Neuroimaging . 2011 ; 21 ( 2 ): e64 - 68 . Google Scholar CrossRef Search ADS PubMed 18. van der Kolk AG , Zwanenburg JJM , Denswil NP et al. Imaging the intracranial atherosclerotic vessel wall using 7T MRI: initial comparison with histopathology . AJNR Am J Neuroradiol . 2015 ; 36 ( 4 ): 694 - 701 . Google Scholar CrossRef Search ADS PubMed 19. Kim SK , Yoon W , Heo TW , Park MS , Kang HK . Negative susceptibility vessel sign and underlying intracranial atherosclerotic stenosis in acute middle cerebral artery occlusion . AJNR Am J Neuroradiol . 2105 ; 36 ( 7 ): 1266 - 1271 . Google Scholar CrossRef Search ADS 20. Zaidat OO , Yoo AJ , Khatri P et al. Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement . Stroke . 2013 ; 44 ( 9 ): 2650 - 2663 . Google Scholar CrossRef Search ADS PubMed 21. Lee JS , Hong JM , Lee KS , Suh HI , Choi JW , Kim SY . Primary stent retrieval for acute intracranial large artery occlusion due to atherosclerotic disease . J Stroke . 2016 ; 18 ( 1 ): 96 - 101 . Google Scholar CrossRef Search ADS PubMed 22. Cho KH , Kim JS , Kwon SU , Cho AH , Kang DW . Significance of susceptibility vessel sign on T2*-weighted gradient echo imaging for identification of stroke subtypes . Stroke . 2005 ; 36 ( 1 ): 2379 - 2383 . Google Scholar CrossRef Search ADS PubMed 23. Kim EY , Yoo E , Choi HY , Lee JW , Heo JH . Thrombus volume comparison between patients with and without hyperattenuated artery sign on CT . AJNR Am J Neuroradiol . 2008 ; 29 ( 2 ): 359 - 62 . doi: 10.3174/ajnr.A0800 . Google Scholar CrossRef Search ADS PubMed 24. Moftakhar P , English JD , Cooke DL et al. Density of thrombus on admission CT predicts revascularization efficacy in large vessel occlusion acute ischemic stroke . Stroke . 2013 ; 44 ( 1 ): 243 - 245 . Google Scholar CrossRef Search ADS PubMed 25. Kirchhof K , Welzel T , Mecke C , Zoubaa S , Sartor K . Differentiation of white, mixed, and red thrombi: value of CT in estimation of the prognosis of thrombolysis phantom study . Radiology . 2003 ; 228 ( 1 ): 126 - 130 . Google Scholar CrossRef Search ADS PubMed 26. Tan IYL , Demchuk AM , Hopyan J et al. CT angiography clot burden score and collateral score: correlation with clinical and radiologic outcomes in acute middle cerebral artery infarct . AJNR Am J Neuroradiol . 2009 ; 30 ( 3 ): 525 - 531 . Google Scholar CrossRef Search ADS PubMed 27. Protto S , Sillanpää N , Pienimäki J-P et al. Stent retriever thrombectomy in different thrombus locations of anterior cerebral circulation . Cardiovasc Intervent Radiol . 2016 ; 39 ( 7 ): 988 - 993 . Google Scholar CrossRef Search ADS PubMed 28. Siebler M , Hennerici MG , Schneider D et al. Safety of Tirofiban in acute ischemic stroke: the SaTIS trial . Stroke . 2011 ; 42 ( 9 ): 2388 - 2392 . Google Scholar CrossRef Search ADS PubMed 29. Gory B , Bresson D , Kessler I et al. Histopathologic evaluation of arterial wall response to 5 neurovascular mechanical thrombectomy devices in a swine model . AJNR Am J Neuroradiol . 2013 ; 34 ( 11 ): 2192 - 2198 . Google Scholar CrossRef Search ADS PubMed COMMENT The authors present a method for differentiating intracranial atherosclerotic disease (ICAS) from an intracranial embolism in the evaluation of acute ischemic stroke. Using what they describe as a “first-pass effect” whereby temporary angiographic blood flow is seen distal to an occlusion after a microcatheter is passed through the blockage and immediately retrieved. The microcatheter first-pass effect was observed more frequently in the ICAS population with an accuracy of 88.5%. The authors postulate that the white thrombus usually seen with ICAS is less dense than the red thrombus associated with a cardiogenic source and as such remains patent transiently after the microcatheter is withdrawn. A blockage that displays a positive first-pass effect is theoretically less likely to respond to mechanical thrombectomy because of the underlying disease. ICAS lesions should be treated with antiplatelet agents and angioplasty with/without stenting. Knowing the origin of the occlusion should help the interventionist tailor the treatment, which would save time and expense. Jay U. Howington Savannah, Georgia Copyright © 2018 by the Congress of Neurological Surgeons This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurosurgery Oxford University Press

Microcatheter “First-Pass Effect” Predicts Acute Intracranial Artery Atherosclerotic Disease-Related Occlusion

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Oxford University Press
Copyright
Copyright © 2018 by the Congress of Neurological Surgeons
ISSN
0148-396X
eISSN
1524-4040
D.O.I.
10.1093/neuros/nyy183
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Abstract

Abstract BACKGROUND The differentiation between intracranial atherosclerotic stenosis (ICAS) and intracranial embolism as the immediate cause of acute ischemic stroke requiring endovascular therapy is important but challenging. In cases of ICAS, we often observe a phenomenon we call the microcatheter “first-pass effect,” which is temporary blood flow through the occluded intracranial artery when the angiographic microcatheter is initially advanced through the site of total occlusion and immediately retrieved proximally. OBJECTIVE To evaluate whether this microcatheter first-pass effect can be used to differentiate ICAS from intracranial embolism. METHODS A total of 61 patients with acute ischemic stroke resulting from large intracranial artery occlusion and in whom recanalization was achieved by endovascular treatment were included in the study. The microcatheter first-pass effect was tested in these patients. The sensitivity, specificity, positive predictive values (PPV), and accuracy of the microcatheter first-pass effect for prediction of ICAS were assessed. RESULTS The microcatheter first-pass effect was more frequently observed in patients with ICAS than in those with intracranial embolism (90.9% vs 12.8%, P < .001). For identifying ICAS, sensitivity, specificity, PPV, and accuracy of the microcatheter first-pass effect were 90.9%, 87.2%, 80.0%, 88.5%, respectively. CONCLUSION The sensitivity and PPV of the microcatheter first-pass effect are high for prediction of ICAS in patients with acute symptoms. Acute ischemic stroke, Intracranial atherosclerotic stenosis, Intracranial embolism, Endovascular therapy, Sensitivity ABBREVIATIONS ABBREVIATIONS ACG American Society of Interventional and Therapeutic Neuroradiology collateral grading scale BA basilar artery CTA computed tomography angiography HAS hyperdense artery sign ICA internal carotid artery ICAS Intracranial atherosclerotic stenosis MCA middle cerebral artery MR magnetic resonance MRA magnetic resonance angiography mRS modified Rankin Scale NIHSS NIH Stroke Scale NPV negative predictive value PPV positive predictive value TICI thrombolysis in cerebral infarction Intracranial atherosclerosis is common in Asia, and it accounts for 25% to 50% of ischemic strokes.1,2 The reported incidence of acute occlusion resulting from intracranial atherosclerotic stenosis (ICAS) is 22.9% in Asia3 and 5.5% in western countries.4 Mechanical thrombectomy is an effective treatment for acute ischemic stroke caused by intracranial artery occlusion,5-10 but it was designed primarily for embolic occlusion rather than ICAS.11 Although mechanical thrombectomy results in reperfusion, reocclusion often occurs at the site of the ICAS due to subsequent platelet aggregation.12,13 Thus, rescue therapy such as emergency angioplasty or stenting3,13,14 is often required. For these reasons, it is very important to differentiate ICAS from intracranial embolism. ICAS can be detected and evaluated by means of high-resolution vessel wall magnetic resonance (MR) imaging.15-19 However, such imaging must be performed on a 3.0T or 7.0T MR scanner, neither of which is housed by most municipal hospitals. In addition, the MR studies are time-consuming and require the patient's cooperation. Being able to differentiate ICAS from intracranial embolism during endovascular intervention would be a practical and time-saving solution to the problem. Endovascular intervention has become standard treatment for acute occlusion of a large intracranial artery, with more and more patients receiving such therapy. We have observed, especially in cases of ICAS, a phenomenon we refer to as the microcatheter “first-pass effect.” We found that blood flows slowly and temporarily through the vessel lumen at the site of occlusion when the angiographic microcatheter is advanced through the area of total occlusion and then retrieved on the proximal side of the occlusion. Thus, we conducted a retrospective study to evaluate whether the microcatheter first-pass effect observed during digital subtraction angiography can be used to differentiate ICAS from intracranial embolism. METHODS Study Patients The study included 61 patients who were identified from our registry database of consecutive acute stroke patients treated with endovascular therapy between January 2015 and mid-October 2016. The selected patients met the following criteria: (1) the ischemic stroke resulted from occlusion of a large intracranial artery; (2) the time between symptom onset and admission was 8 h or less in the case of acute anterior circulation infarct or 24 h or less in the case of acute posterior circulation infarct, or the time between symptom onset and admission was beyond the 8 or 24 h, but endovascular therapy was to be performed for a moderate-to-large hypoperfusion area as depicted by multimodal MR imaging; (3) endovascular reperfusion therapy was performed, and successful recanalization was confirmed; (4) the age was above 18 yr; and (5) the prestroke modified Rankin Scale (mRS) score was 0 to 1. Patients were excluded from the study if (1) the stroke was the result of dissection, moyamoya disease, or vasculitis; (2) the stroke was the result of tandem occlusion; or (3) the specific cause of the intracranial large artery occlusion was not determined. Our access to patients’ records for data collection and analysis of the data were approved by our local medical ethics committee. All patients provided informed consent for their clinical data to be used anonymously for research purposes. Operational Definitions of ICAS and Embolic Occlusion ICAS was differentiated from intracranial embolism collaboratively based on angiographic findings. ICAS was defined as a significant fixed focal stenosis at the site of occlusion evidenced by final angiography or during endovascular treatment.11 In addition, the stenosis could be resolved by means of angioplasty or stent insertion. Significant stenosis was defined as (1) fixed stenosis ≥70% or (2) fixed stenosis ≥50% in addition to either angiographically evident impaired perfusion or evidence of re-occlusion following sufficient treatment with a stent retriever. The underlying disorder was classified as embolism based on the following: (1) there was no evidence of focal stenosis after clot retrieval; (2) an embolus was removed with a stent retriever; and (3) MR angiography (MRA) or computed tomography angiography (CTA) performed within 1 wk after the procedure showed the responsible artery to be patent without any stenosis. Definition of the Microcatheter First-Pass Effect A schematic diagram of the first-pass effect is shown in Figure 1. When acute occlusion of a large intracranial artery is seen angiographically (Figure 1A), the following procedure is performed before thrombectomy. A microcatheter and a microwire are navigated through the area of total occlusion to the distal patent artery (Figure 1B). The microcatheter is then retrieved on the proximal side of the thrombus. Angiography is performed with a guiding catheter or microcatheter to determine whether blood flows through the vessel at the site of occlusion. Such flow is recorded as the microcatheter first-pass effect (Figure 1C). If there is no such flow, absence of the first-pass effect is noted (Figure 1D). The first-pass effect is confirmed by 2 experienced neuro-interventionists who are present during the procedure. FIGURE 1. View largeDownload slide Schematic diagram of the first-pass effect. A, Left middle cerebral artery is occluded by a thrombus. B, The angiographic microcatheter is navigated through the thrombus over a microwire. C and D, The microcatheter is retrieved with the microwire remaining in place. C Slow blood flow in the distal artery beyond the thrombus is the so-called first-pass effect. D, The absence of blood flow is absence of the first-pass effect. FIGURE 1. View largeDownload slide Schematic diagram of the first-pass effect. A, Left middle cerebral artery is occluded by a thrombus. B, The angiographic microcatheter is navigated through the thrombus over a microwire. C and D, The microcatheter is retrieved with the microwire remaining in place. C Slow blood flow in the distal artery beyond the thrombus is the so-called first-pass effect. D, The absence of blood flow is absence of the first-pass effect. Clinical and Radiological Assessment We assessed neurological function of all study patients upon admission by means of the NIH Stroke Scale (NIHSS). We then assessed patients radiologically based on the Thrombolysis in Cerebral Infarction (TICI) scale, American Society of Interventional and Therapeutic Neuroradiology collateral grading (ACG) system, and the site of occlusion, as shown in Table 1. Successful reperfusion was defined as a TICI grade of 2b or 3 after endovascular treatment, and good preprocedural collateral flow was defined as an ACG score ≥3.20 High-resolution MR imaging was performed in some patients with ICAS who did not undergo stenting. TABLE 1. Radiological Assessment Items and Their Definitions Item Definition mTICI grade • Grade 0 No perfusion • Grade 1 Antegrade reperfusion past the initial occlusion, but limited distal branch filling with little or slow distal reperfusion • Grade 2a Antegrade reperfusion of less than half of the occluded target artery previously ischemic territory • Grade 2b Antegrade reperfusion of more than half of the previously occluded target artery ischemic territory • Grade 3 Complete antegrade reperfusion of the previously occluded target artery ischemic territory, with absence of visualized occlusion in all distal branches ACG grade • Grade 0 No collaterals visible to the ischemic site • Grade 1 Slow collaterals to the periphery of the ischemic site, with persistence of some of the defect • Grade 2 Rapid collaterals to the periphery of the ischemic site, with persistence of the defect, and only to a portion of the ischemic territory • Grade 3 Collaterals with slow but complete angiographic blood flow of the ischemic bed by the late venous phase • Grade 4 Complete and rapid collateral blood flow to the vascular bed in the entire ischemic territory by retrograde perfusion Intracranial ICA occlusion • Carotid T if the terminal ICA, M1, and A1 are occluded • Carotid L if both the terminal ICA and M1 are occluded (A1 is spared) • Carotid I if only the terminal ICA is occluded (M1 and A1 are spared) MCA segment clot location • The M1 segment is taken as the first portion of the MCA to the major bifurcation • Clot is localized to the proximal or distal M1 segment according to which half of the segment is involved and whether the lenticulostriates are involved (proximal) or spared (distal) Item Definition mTICI grade • Grade 0 No perfusion • Grade 1 Antegrade reperfusion past the initial occlusion, but limited distal branch filling with little or slow distal reperfusion • Grade 2a Antegrade reperfusion of less than half of the occluded target artery previously ischemic territory • Grade 2b Antegrade reperfusion of more than half of the previously occluded target artery ischemic territory • Grade 3 Complete antegrade reperfusion of the previously occluded target artery ischemic territory, with absence of visualized occlusion in all distal branches ACG grade • Grade 0 No collaterals visible to the ischemic site • Grade 1 Slow collaterals to the periphery of the ischemic site, with persistence of some of the defect • Grade 2 Rapid collaterals to the periphery of the ischemic site, with persistence of the defect, and only to a portion of the ischemic territory • Grade 3 Collaterals with slow but complete angiographic blood flow of the ischemic bed by the late venous phase • Grade 4 Complete and rapid collateral blood flow to the vascular bed in the entire ischemic territory by retrograde perfusion Intracranial ICA occlusion • Carotid T if the terminal ICA, M1, and A1 are occluded • Carotid L if both the terminal ICA and M1 are occluded (A1 is spared) • Carotid I if only the terminal ICA is occluded (M1 and A1 are spared) MCA segment clot location • The M1 segment is taken as the first portion of the MCA to the major bifurcation • Clot is localized to the proximal or distal M1 segment according to which half of the segment is involved and whether the lenticulostriates are involved (proximal) or spared (distal) mTICI, modified Treatment in Cerebral Ischaemia score; ACG, American Society of Interventional and Therapeutic Neuroradiology Collateral grading system; ICA, internal carotid artery; MCA, middle cerebral artery. View Large TABLE 1. Radiological Assessment Items and Their Definitions Item Definition mTICI grade • Grade 0 No perfusion • Grade 1 Antegrade reperfusion past the initial occlusion, but limited distal branch filling with little or slow distal reperfusion • Grade 2a Antegrade reperfusion of less than half of the occluded target artery previously ischemic territory • Grade 2b Antegrade reperfusion of more than half of the previously occluded target artery ischemic territory • Grade 3 Complete antegrade reperfusion of the previously occluded target artery ischemic territory, with absence of visualized occlusion in all distal branches ACG grade • Grade 0 No collaterals visible to the ischemic site • Grade 1 Slow collaterals to the periphery of the ischemic site, with persistence of some of the defect • Grade 2 Rapid collaterals to the periphery of the ischemic site, with persistence of the defect, and only to a portion of the ischemic territory • Grade 3 Collaterals with slow but complete angiographic blood flow of the ischemic bed by the late venous phase • Grade 4 Complete and rapid collateral blood flow to the vascular bed in the entire ischemic territory by retrograde perfusion Intracranial ICA occlusion • Carotid T if the terminal ICA, M1, and A1 are occluded • Carotid L if both the terminal ICA and M1 are occluded (A1 is spared) • Carotid I if only the terminal ICA is occluded (M1 and A1 are spared) MCA segment clot location • The M1 segment is taken as the first portion of the MCA to the major bifurcation • Clot is localized to the proximal or distal M1 segment according to which half of the segment is involved and whether the lenticulostriates are involved (proximal) or spared (distal) Item Definition mTICI grade • Grade 0 No perfusion • Grade 1 Antegrade reperfusion past the initial occlusion, but limited distal branch filling with little or slow distal reperfusion • Grade 2a Antegrade reperfusion of less than half of the occluded target artery previously ischemic territory • Grade 2b Antegrade reperfusion of more than half of the previously occluded target artery ischemic territory • Grade 3 Complete antegrade reperfusion of the previously occluded target artery ischemic territory, with absence of visualized occlusion in all distal branches ACG grade • Grade 0 No collaterals visible to the ischemic site • Grade 1 Slow collaterals to the periphery of the ischemic site, with persistence of some of the defect • Grade 2 Rapid collaterals to the periphery of the ischemic site, with persistence of the defect, and only to a portion of the ischemic territory • Grade 3 Collaterals with slow but complete angiographic blood flow of the ischemic bed by the late venous phase • Grade 4 Complete and rapid collateral blood flow to the vascular bed in the entire ischemic territory by retrograde perfusion Intracranial ICA occlusion • Carotid T if the terminal ICA, M1, and A1 are occluded • Carotid L if both the terminal ICA and M1 are occluded (A1 is spared) • Carotid I if only the terminal ICA is occluded (M1 and A1 are spared) MCA segment clot location • The M1 segment is taken as the first portion of the MCA to the major bifurcation • Clot is localized to the proximal or distal M1 segment according to which half of the segment is involved and whether the lenticulostriates are involved (proximal) or spared (distal) mTICI, modified Treatment in Cerebral Ischaemia score; ACG, American Society of Interventional and Therapeutic Neuroradiology Collateral grading system; ICA, internal carotid artery; MCA, middle cerebral artery. View Large Patients’ clinical characteristics, risk factors for arteriosclerosis, heart disease, preoperational intravenous thrombolysis, prior stroke, the hyperdense artery sign (HAS) on non-enhanced CT, the NIHSS score upon admission, and angiographic information were recorded. Two neurologists, blinded to the patient information and study protocol, independently studied all images retrospectively. Discrepancies between the reviewers were resolved by consensus. Statistical Analysis Differences in clinical characteristics, risk factors, and imaging features between patients in whom the microcatheter first-pass effect was observed and those in whom it was not observed were examined by bivariate analysis. Differences in clinical characteristics, risk factors, imaging features, and treatment strategies between patients with ICAS and those with intracranial embolism were also examined by bivariate analysis. Student's t-test or the Mann–Whitney U-test was applied to continuous variables, and the χ2 test was applied to categorical variables. Measures of diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of the microcatheter first-pass effect for the prediction of ICAS, were calculated. All statistical analyses were performed with IBM SPSS Statistics 22.0 (IBM Inc, Armonk, New York), and P ≤ .05 was considered significant. RESULTS Patients in Whom the Microcatheter First-Pass Effect was Observed vs Patients in Whom it was not Observed The microcatheter first-pass effect was observed in 25 (41.0%) of the 61 study patients (Figure 2). Clinical characteristics are shown for patients in the first-pass effect group vs patients in the non-first-pass effect group in Table 2. Patients in the first-pass effect group, in comparison to those in the non-first-pass effect group (Figure 3), were more likely to be male (76.0% vs 47.2%, P = .025), more likely to have hypertension (80.0% vs 44.4%, P = .005), less likely to have atrial fibrillation and/or rheumatoid heart disease (12.0% vs 77.8%, P < .001), less likely to show the HAS on non-enhanced CT (21.6% vs 78.8%, P < .001), and less likely to have carotid T occlusion (0% vs 33.3%, P = .004). The collateral flow was better in the microcatheter first-pass effect group than in the non-first-pass effect group (ACG ≥ 3, 50.0% vs 18.8%, P = .015). FIGURE 2. View largeDownload slide Illustrative cases of the microcatheter first-pass effect. A 52-yr-old male smoker presented with right hemiparesis and aphasia. A, DSA revealed total occlusion of the terminal segment of the left ICA (black arrow). B, The microcatheter first-pass effect without focal stenosis was observed (black arrow indicates the distal end of the proximally retrieved the retrieved microcatheter). C, A 6.0-mm × 30-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through the site. D, Severe stenosis was seen after a single pass of the stent retriever (black arrow). E, Postoperative MRA showed severe stenosis of the terminal segment of the left ICA (black arrow), and the high-solution MR (TIWI) image at the bottom right shows an irregular plaque within the terminal segment of the left ICA (white arrowhead). A 78-yr-old male smoker presented with left hemiparesis. F, DSA revealed total occlusion of the right distal MCA (black arrow). G, The microcatheter first-pass effect without focal stenosis was observed. Slow blood flow was seen (black arrow) when the microcatheter was retrieved back to the proximal to the thrombus. H, A 4.0-mm × 20-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through the site. I, TICI grade 3 recanalization was achieved after a single pass of the stent retriever. J, Postoperative MRA confirmed the patency of the right MCA. DSA indicates digital subtraction angiography; ICA, internal carotid artery; MCA, middle cerebral artery. FIGURE 2. View largeDownload slide Illustrative cases of the microcatheter first-pass effect. A 52-yr-old male smoker presented with right hemiparesis and aphasia. A, DSA revealed total occlusion of the terminal segment of the left ICA (black arrow). B, The microcatheter first-pass effect without focal stenosis was observed (black arrow indicates the distal end of the proximally retrieved the retrieved microcatheter). C, A 6.0-mm × 30-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through the site. D, Severe stenosis was seen after a single pass of the stent retriever (black arrow). E, Postoperative MRA showed severe stenosis of the terminal segment of the left ICA (black arrow), and the high-solution MR (TIWI) image at the bottom right shows an irregular plaque within the terminal segment of the left ICA (white arrowhead). A 78-yr-old male smoker presented with left hemiparesis. F, DSA revealed total occlusion of the right distal MCA (black arrow). G, The microcatheter first-pass effect without focal stenosis was observed. Slow blood flow was seen (black arrow) when the microcatheter was retrieved back to the proximal to the thrombus. H, A 4.0-mm × 20-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through the site. I, TICI grade 3 recanalization was achieved after a single pass of the stent retriever. J, Postoperative MRA confirmed the patency of the right MCA. DSA indicates digital subtraction angiography; ICA, internal carotid artery; MCA, middle cerebral artery. FIGURE 2. View largeDownload slide Illustrative cases of the microcatheter first-pass effect. A 52-yr-old male smoker presented with right hemiparesis and aphasia. A, DSA revealed total occlusion of the terminal segment of the left ICA (black arrow). B, The microcatheter first-pass effect without focal stenosis was observed (black arrow indicates the distal end of the proximally retrieved the retrieved microcatheter). C, A 6.0-mm × 30-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through the site. D, Severe stenosis was seen after a single pass of the stent retriever (black arrow). E, Postoperative MRA showed severe stenosis of the terminal segment of the left ICA (black arrow), and the high-solution MR (TIWI) image at the bottom right shows an irregular plaque within the terminal segment of the left ICA (white arrowhead). A 78-yr-old male smoker presented with left hemiparesis. F, DSA revealed total occlusion of the right distal MCA (black arrow). G, The microcatheter first-pass effect without focal stenosis was observed. Slow blood flow was seen (black arrow) when the microcatheter was retrieved back to the proximal to the thrombus. H, A 4.0-mm × 20-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through the site. I, TICI grade 3 recanalization was achieved after a single pass of the stent retriever. J, Postoperative MRA confirmed the patency of the right MCA. DSA indicates digital subtraction angiography; ICA, internal carotid artery; MCA, middle cerebral artery. FIGURE 2. View largeDownload slide Illustrative cases of the microcatheter first-pass effect. A 52-yr-old male smoker presented with right hemiparesis and aphasia. A, DSA revealed total occlusion of the terminal segment of the left ICA (black arrow). B, The microcatheter first-pass effect without focal stenosis was observed (black arrow indicates the distal end of the proximally retrieved the retrieved microcatheter). C, A 6.0-mm × 30-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through the site. D, Severe stenosis was seen after a single pass of the stent retriever (black arrow). E, Postoperative MRA showed severe stenosis of the terminal segment of the left ICA (black arrow), and the high-solution MR (TIWI) image at the bottom right shows an irregular plaque within the terminal segment of the left ICA (white arrowhead). A 78-yr-old male smoker presented with left hemiparesis. F, DSA revealed total occlusion of the right distal MCA (black arrow). G, The microcatheter first-pass effect without focal stenosis was observed. Slow blood flow was seen (black arrow) when the microcatheter was retrieved back to the proximal to the thrombus. H, A 4.0-mm × 20-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through the site. I, TICI grade 3 recanalization was achieved after a single pass of the stent retriever. J, Postoperative MRA confirmed the patency of the right MCA. DSA indicates digital subtraction angiography; ICA, internal carotid artery; MCA, middle cerebral artery. TABLE 2. Clinical Characteristics of Patients in Whom the Microcatheter First-Pass Effect was Seen and Patients in Whom it was not Seen First-pass Effect (n = 25) No First-pass Effect (n = 36) P value Sex (male, n) 19 (76.0%) 17 (47.2%) .025 Age (mean, years) 62 ± 11 64 ± 9 .522 Smoker 16(64.0%) 16 (44.4%) .133 Hypertension n (%) 18 (80.0%) 16(44.4%) .005 Diabetes mellitus, n (%) 4 (16.0%) 4(11.1%) .864 Hyperlipidemia, n (%) 4(16.0%) 3(8.3%) .606 Atrial fibrillation and/or rheumatic heart disease 3 (12.0%) 28 (77.8%) <.001 Transient ischemic attack 2(8.0%) 0 (0%) .056 Admission NHISS 15.9 ± 6 18.2 ± 5 .110 Intravenous thrombolysis, n (%) 8 (32.0%) 9 (25.0%) .549 HAS on CT, n (%)a 6 (21.6%) 26 (78.8%) <.001 Occlusion classification/site, n (%)  ICA terminus   Carotid T 0 (0%) 12 (33.3%) .004   Carotid L 2 (8.0%) 2 (5.6%) 1.000   Isolated intracranial ICA 4(16.0%) 3 (8.3%) .606  MCA   M1 segment-proximal 11 (44.0%) 11 (25.0%) .120   M1 segment-distal 5 (20.0%) 7 (19.4%) 1.000  BA 3 (12.0%) 4 (11.1%) 1.000 Good collateral flow,b n (%) .015  ACG ≥ 3 11/22(50.0%) 6/32(18.8%) First-pass Effect (n = 25) No First-pass Effect (n = 36) P value Sex (male, n) 19 (76.0%) 17 (47.2%) .025 Age (mean, years) 62 ± 11 64 ± 9 .522 Smoker 16(64.0%) 16 (44.4%) .133 Hypertension n (%) 18 (80.0%) 16(44.4%) .005 Diabetes mellitus, n (%) 4 (16.0%) 4(11.1%) .864 Hyperlipidemia, n (%) 4(16.0%) 3(8.3%) .606 Atrial fibrillation and/or rheumatic heart disease 3 (12.0%) 28 (77.8%) <.001 Transient ischemic attack 2(8.0%) 0 (0%) .056 Admission NHISS 15.9 ± 6 18.2 ± 5 .110 Intravenous thrombolysis, n (%) 8 (32.0%) 9 (25.0%) .549 HAS on CT, n (%)a 6 (21.6%) 26 (78.8%) <.001 Occlusion classification/site, n (%)  ICA terminus   Carotid T 0 (0%) 12 (33.3%) .004   Carotid L 2 (8.0%) 2 (5.6%) 1.000   Isolated intracranial ICA 4(16.0%) 3 (8.3%) .606  MCA   M1 segment-proximal 11 (44.0%) 11 (25.0%) .120   M1 segment-distal 5 (20.0%) 7 (19.4%) 1.000  BA 3 (12.0%) 4 (11.1%) 1.000 Good collateral flow,b n (%) .015  ACG ≥ 3 11/22(50.0%) 6/32(18.8%) aPlain CT not done for 5 patients. bIn the anterior circulation. NHISS indicates NIH stroke scale; HAS, hyper-dense artery signs; ICA, internal carotid artery; MCA, middle cerebral artery; BA, basilar artery; ACG, American Society of Interventional and Therapeutic Neuroradiology collateral grading system. View Large TABLE 2. Clinical Characteristics of Patients in Whom the Microcatheter First-Pass Effect was Seen and Patients in Whom it was not Seen First-pass Effect (n = 25) No First-pass Effect (n = 36) P value Sex (male, n) 19 (76.0%) 17 (47.2%) .025 Age (mean, years) 62 ± 11 64 ± 9 .522 Smoker 16(64.0%) 16 (44.4%) .133 Hypertension n (%) 18 (80.0%) 16(44.4%) .005 Diabetes mellitus, n (%) 4 (16.0%) 4(11.1%) .864 Hyperlipidemia, n (%) 4(16.0%) 3(8.3%) .606 Atrial fibrillation and/or rheumatic heart disease 3 (12.0%) 28 (77.8%) <.001 Transient ischemic attack 2(8.0%) 0 (0%) .056 Admission NHISS 15.9 ± 6 18.2 ± 5 .110 Intravenous thrombolysis, n (%) 8 (32.0%) 9 (25.0%) .549 HAS on CT, n (%)a 6 (21.6%) 26 (78.8%) <.001 Occlusion classification/site, n (%)  ICA terminus   Carotid T 0 (0%) 12 (33.3%) .004   Carotid L 2 (8.0%) 2 (5.6%) 1.000   Isolated intracranial ICA 4(16.0%) 3 (8.3%) .606  MCA   M1 segment-proximal 11 (44.0%) 11 (25.0%) .120   M1 segment-distal 5 (20.0%) 7 (19.4%) 1.000  BA 3 (12.0%) 4 (11.1%) 1.000 Good collateral flow,b n (%) .015  ACG ≥ 3 11/22(50.0%) 6/32(18.8%) First-pass Effect (n = 25) No First-pass Effect (n = 36) P value Sex (male, n) 19 (76.0%) 17 (47.2%) .025 Age (mean, years) 62 ± 11 64 ± 9 .522 Smoker 16(64.0%) 16 (44.4%) .133 Hypertension n (%) 18 (80.0%) 16(44.4%) .005 Diabetes mellitus, n (%) 4 (16.0%) 4(11.1%) .864 Hyperlipidemia, n (%) 4(16.0%) 3(8.3%) .606 Atrial fibrillation and/or rheumatic heart disease 3 (12.0%) 28 (77.8%) <.001 Transient ischemic attack 2(8.0%) 0 (0%) .056 Admission NHISS 15.9 ± 6 18.2 ± 5 .110 Intravenous thrombolysis, n (%) 8 (32.0%) 9 (25.0%) .549 HAS on CT, n (%)a 6 (21.6%) 26 (78.8%) <.001 Occlusion classification/site, n (%)  ICA terminus   Carotid T 0 (0%) 12 (33.3%) .004   Carotid L 2 (8.0%) 2 (5.6%) 1.000   Isolated intracranial ICA 4(16.0%) 3 (8.3%) .606  MCA   M1 segment-proximal 11 (44.0%) 11 (25.0%) .120   M1 segment-distal 5 (20.0%) 7 (19.4%) 1.000  BA 3 (12.0%) 4 (11.1%) 1.000 Good collateral flow,b n (%) .015  ACG ≥ 3 11/22(50.0%) 6/32(18.8%) aPlain CT not done for 5 patients. bIn the anterior circulation. NHISS indicates NIH stroke scale; HAS, hyper-dense artery signs; ICA, internal carotid artery; MCA, middle cerebral artery; BA, basilar artery; ACG, American Society of Interventional and Therapeutic Neuroradiology collateral grading system. View Large FIGURE 3. View largeDownload slide Illustrative cases of the absence of the microcatheter first-pass effect. A 71-yr-old man presented with quadriplegia and drowsiness. A, DSA showed total occlusion of the proximal BA (black arrow). B, The microcatheter first-pass effect was not seen (black arrow indicates the distal end of the retrieved microcatheter). C, An angiogram obtained when the stent retriever was unsheathed at the second time revealed a high clot burden (black arrow). D, 60% stenosis was observed at the site of proximal BA occlusion after 2 passes of the stent retriever followed by emergency angioplasty performed with a 2.5-mm × 9-mm Gateway balloon. E, Postoperative MRA revealed severe BA stenosis. A 59-yr-old man presented with left hemiparesis. F, DSA showed total occlusion of the right proximal MCA (black arrow). G, The microcatheter first-pass effect was not seen (black arrow indicates the distal end of the retrieved microcatheter). H, A 4.0-mm × 20-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through. I, TICI grade 3 recanalization was achieved after a single pass of the stent retriever. J, Postoperative MRA showed the right MCA to be patent. DSA indicates digital subtraction angiography, BA, basilar artery, MCA, middle cerebral artery. FIGURE 3. View largeDownload slide Illustrative cases of the absence of the microcatheter first-pass effect. A 71-yr-old man presented with quadriplegia and drowsiness. A, DSA showed total occlusion of the proximal BA (black arrow). B, The microcatheter first-pass effect was not seen (black arrow indicates the distal end of the retrieved microcatheter). C, An angiogram obtained when the stent retriever was unsheathed at the second time revealed a high clot burden (black arrow). D, 60% stenosis was observed at the site of proximal BA occlusion after 2 passes of the stent retriever followed by emergency angioplasty performed with a 2.5-mm × 9-mm Gateway balloon. E, Postoperative MRA revealed severe BA stenosis. A 59-yr-old man presented with left hemiparesis. F, DSA showed total occlusion of the right proximal MCA (black arrow). G, The microcatheter first-pass effect was not seen (black arrow indicates the distal end of the retrieved microcatheter). H, A 4.0-mm × 20-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through. I, TICI grade 3 recanalization was achieved after a single pass of the stent retriever. J, Postoperative MRA showed the right MCA to be patent. DSA indicates digital subtraction angiography, BA, basilar artery, MCA, middle cerebral artery. FIGURE 3. View largeDownload slide Illustrative cases of the absence of the microcatheter first-pass effect. A 71-yr-old man presented with quadriplegia and drowsiness. A, DSA showed total occlusion of the proximal BA (black arrow). B, The microcatheter first-pass effect was not seen (black arrow indicates the distal end of the retrieved microcatheter). C, An angiogram obtained when the stent retriever was unsheathed at the second time revealed a high clot burden (black arrow). D, 60% stenosis was observed at the site of proximal BA occlusion after 2 passes of the stent retriever followed by emergency angioplasty performed with a 2.5-mm × 9-mm Gateway balloon. E, Postoperative MRA revealed severe BA stenosis. A 59-yr-old man presented with left hemiparesis. F, DSA showed total occlusion of the right proximal MCA (black arrow). G, The microcatheter first-pass effect was not seen (black arrow indicates the distal end of the retrieved microcatheter). H, A 4.0-mm × 20-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through. I, TICI grade 3 recanalization was achieved after a single pass of the stent retriever. J, Postoperative MRA showed the right MCA to be patent. DSA indicates digital subtraction angiography, BA, basilar artery, MCA, middle cerebral artery. FIGURE 3. View largeDownload slide Illustrative cases of the absence of the microcatheter first-pass effect. A 71-yr-old man presented with quadriplegia and drowsiness. A, DSA showed total occlusion of the proximal BA (black arrow). B, The microcatheter first-pass effect was not seen (black arrow indicates the distal end of the retrieved microcatheter). C, An angiogram obtained when the stent retriever was unsheathed at the second time revealed a high clot burden (black arrow). D, 60% stenosis was observed at the site of proximal BA occlusion after 2 passes of the stent retriever followed by emergency angioplasty performed with a 2.5-mm × 9-mm Gateway balloon. E, Postoperative MRA revealed severe BA stenosis. A 59-yr-old man presented with left hemiparesis. F, DSA showed total occlusion of the right proximal MCA (black arrow). G, The microcatheter first-pass effect was not seen (black arrow indicates the distal end of the retrieved microcatheter). H, A 4.0-mm × 20-mm Solitaire stent (black arrow) was unsheathed at the occlusion site, and blood flowed through. I, TICI grade 3 recanalization was achieved after a single pass of the stent retriever. J, Postoperative MRA showed the right MCA to be patent. DSA indicates digital subtraction angiography, BA, basilar artery, MCA, middle cerebral artery. Patients With ICAS vs Patients With Embolism ICAS was diagnosed in 22 (36.1%) of the 61 patients. The clinical characteristics are shown for patients in the ICAS group vs patients in the non-ICAS (intracranial embolism) group in Table 3. The ICAS patients were more likely to be male (81.8% vs 46.2%, P = .007), more likely to have hypertension (86.4% vs 43.6%, P = .001), more likely to have suffered a TIA (9.1% vs 0%, P = .040), less likely to have atrial fibrillation and/or rheumatoid heart disease (0% vs 79.5%, P < .001), less likely to show HAS on non-enhanced CT (22.2% vs 73.7%, P < .001), and less likely to have a carotid T occlusion (0% vs 30.8%, P = .010). The collateral flow was better in the ICAS group than in the non-ICAS group (ACG ≥ 3, 58.8% vs 18.9%, P = .003). Nineteen (86.4%) of the 22 ICAS patients required emergency angioplasty for successful recanalization (Table 4). Nine patients with ICAS who did not receive a stent underwent high-resolution MR imaging. The stenosis in these cases was located in the proximal M1 segment (n = 4), the internal carotid terminus segment (n = 3), the distal M1 segment (n = 1), or the basilar artery (BA; n = 1). Stenosis of the responsible artery was observed in time-of-flight MRA, with irregular arteriosclerotic plaques of various thicknesses observed on volume isotropic turbo spin echo acquisition images in all 9 cases. TABLE 3. Clinical Characteristics of Patients in the ICAS Group and Embolism Group ICAS group (n = 22) Embolism group (n = 39) P value Sex (male, n) 18(81.8%) 18 (46.2%) .007 Age (mean, years) 61 ± 10 65 ± 10 .114 Smoker 17 (77.3%) 15 (38.5%) .004 Hypertension, n (%) 19 (86.4%) 17 (43.6%) .001 Diabetes mellitus n (%) 3 (13.6%) 5(12.8%) 1.000 Hyperlipidemia, n (%) 5(22.7%) 2 (5.1%) .098 Atrial fibrillation and/or rheumatic heart disease 0(0%) 31(79.5%) < .001 Transient ischemic attack 2 (9.1%) 0 (0%) .040 Admission NHISS 16.9 ± 7 17.4 ± 4 .752 Intravenous thrombolysis, n (%) 4 (18.2%) 13 (33.3%) .205 HAS positive on CT n (%) a 4 (22.2%) 28 (73.7%) < .001 Occlusion classification/site, n (%)  ICA terminus   Carotid T 0 (0%) 12 (30.8%) .010   Carotid L 2 (9.1%) 2 (5.1%) .951   Isolated intracranial ICA 4 (18.2%) 3 (7.7%) .414  MCA   M1 segment-proximal 10 (45.5%) 10 (25.6%) .113   M1 segment-Distal 1(4.5%) 11 (28.2%) .058  BA 5 (22.7%) 2 (5.1%) .098 Good collateral flowb, n (%)a .003  ACG ≥ 3 10/17 (58.8%) 7/37 (18.9%) Microcatheter first pass ‘‘effect’’ 20 (90.9%) 5 (12.8%) < .001 ICAS group (n = 22) Embolism group (n = 39) P value Sex (male, n) 18(81.8%) 18 (46.2%) .007 Age (mean, years) 61 ± 10 65 ± 10 .114 Smoker 17 (77.3%) 15 (38.5%) .004 Hypertension, n (%) 19 (86.4%) 17 (43.6%) .001 Diabetes mellitus n (%) 3 (13.6%) 5(12.8%) 1.000 Hyperlipidemia, n (%) 5(22.7%) 2 (5.1%) .098 Atrial fibrillation and/or rheumatic heart disease 0(0%) 31(79.5%) < .001 Transient ischemic attack 2 (9.1%) 0 (0%) .040 Admission NHISS 16.9 ± 7 17.4 ± 4 .752 Intravenous thrombolysis, n (%) 4 (18.2%) 13 (33.3%) .205 HAS positive on CT n (%) a 4 (22.2%) 28 (73.7%) < .001 Occlusion classification/site, n (%)  ICA terminus   Carotid T 0 (0%) 12 (30.8%) .010   Carotid L 2 (9.1%) 2 (5.1%) .951   Isolated intracranial ICA 4 (18.2%) 3 (7.7%) .414  MCA   M1 segment-proximal 10 (45.5%) 10 (25.6%) .113   M1 segment-Distal 1(4.5%) 11 (28.2%) .058  BA 5 (22.7%) 2 (5.1%) .098 Good collateral flowb, n (%)a .003  ACG ≥ 3 10/17 (58.8%) 7/37 (18.9%) Microcatheter first pass ‘‘effect’’ 20 (90.9%) 5 (12.8%) < .001 aPlain CT not done for 5 patients. bIn the anterior circulation. NHISS indicates NIH stroke scale; HAS, hyper-dense artery sign; ICA, internal carotid artery; MCA, middle cerebral artery; BA, basilar artery; ACG, American Society of Interventional and Therapeutic Neuroradiology collateral grading system. View Large TABLE 3. Clinical Characteristics of Patients in the ICAS Group and Embolism Group ICAS group (n = 22) Embolism group (n = 39) P value Sex (male, n) 18(81.8%) 18 (46.2%) .007 Age (mean, years) 61 ± 10 65 ± 10 .114 Smoker 17 (77.3%) 15 (38.5%) .004 Hypertension, n (%) 19 (86.4%) 17 (43.6%) .001 Diabetes mellitus n (%) 3 (13.6%) 5(12.8%) 1.000 Hyperlipidemia, n (%) 5(22.7%) 2 (5.1%) .098 Atrial fibrillation and/or rheumatic heart disease 0(0%) 31(79.5%) < .001 Transient ischemic attack 2 (9.1%) 0 (0%) .040 Admission NHISS 16.9 ± 7 17.4 ± 4 .752 Intravenous thrombolysis, n (%) 4 (18.2%) 13 (33.3%) .205 HAS positive on CT n (%) a 4 (22.2%) 28 (73.7%) < .001 Occlusion classification/site, n (%)  ICA terminus   Carotid T 0 (0%) 12 (30.8%) .010   Carotid L 2 (9.1%) 2 (5.1%) .951   Isolated intracranial ICA 4 (18.2%) 3 (7.7%) .414  MCA   M1 segment-proximal 10 (45.5%) 10 (25.6%) .113   M1 segment-Distal 1(4.5%) 11 (28.2%) .058  BA 5 (22.7%) 2 (5.1%) .098 Good collateral flowb, n (%)a .003  ACG ≥ 3 10/17 (58.8%) 7/37 (18.9%) Microcatheter first pass ‘‘effect’’ 20 (90.9%) 5 (12.8%) < .001 ICAS group (n = 22) Embolism group (n = 39) P value Sex (male, n) 18(81.8%) 18 (46.2%) .007 Age (mean, years) 61 ± 10 65 ± 10 .114 Smoker 17 (77.3%) 15 (38.5%) .004 Hypertension, n (%) 19 (86.4%) 17 (43.6%) .001 Diabetes mellitus n (%) 3 (13.6%) 5(12.8%) 1.000 Hyperlipidemia, n (%) 5(22.7%) 2 (5.1%) .098 Atrial fibrillation and/or rheumatic heart disease 0(0%) 31(79.5%) < .001 Transient ischemic attack 2 (9.1%) 0 (0%) .040 Admission NHISS 16.9 ± 7 17.4 ± 4 .752 Intravenous thrombolysis, n (%) 4 (18.2%) 13 (33.3%) .205 HAS positive on CT n (%) a 4 (22.2%) 28 (73.7%) < .001 Occlusion classification/site, n (%)  ICA terminus   Carotid T 0 (0%) 12 (30.8%) .010   Carotid L 2 (9.1%) 2 (5.1%) .951   Isolated intracranial ICA 4 (18.2%) 3 (7.7%) .414  MCA   M1 segment-proximal 10 (45.5%) 10 (25.6%) .113   M1 segment-Distal 1(4.5%) 11 (28.2%) .058  BA 5 (22.7%) 2 (5.1%) .098 Good collateral flowb, n (%)a .003  ACG ≥ 3 10/17 (58.8%) 7/37 (18.9%) Microcatheter first pass ‘‘effect’’ 20 (90.9%) 5 (12.8%) < .001 aPlain CT not done for 5 patients. bIn the anterior circulation. NHISS indicates NIH stroke scale; HAS, hyper-dense artery sign; ICA, internal carotid artery; MCA, middle cerebral artery; BA, basilar artery; ACG, American Society of Interventional and Therapeutic Neuroradiology collateral grading system. View Large TABLE 4. Endovascular Therapy in the ICAS Group and Embolism Group ICAS group (n = 22) Embolism group (n = 39) P value Intracranial artery angioplasty  With balloon 4 (18.2%) 0 (0%) .027  With stent 3 (13.6%) 0 (0%) .080  With balloon and stent 2 (9.1%) 0 (0%) .040  Stenting after clot retrieval 5 (22.7%) 0 (0%) .009  Balloon angioplasty after clot retrieval 4 (18.2%) 0 (0%) .027  With Balloon and stent balloon plus stent 1 (4.5%) 0 (0%) .150 Mechanical thrombectomy 3 (13.6%) 39 (100%) <.001 ICAS group (n = 22) Embolism group (n = 39) P value Intracranial artery angioplasty  With balloon 4 (18.2%) 0 (0%) .027  With stent 3 (13.6%) 0 (0%) .080  With balloon and stent 2 (9.1%) 0 (0%) .040  Stenting after clot retrieval 5 (22.7%) 0 (0%) .009  Balloon angioplasty after clot retrieval 4 (18.2%) 0 (0%) .027  With Balloon and stent balloon plus stent 1 (4.5%) 0 (0%) .150 Mechanical thrombectomy 3 (13.6%) 39 (100%) <.001 View Large TABLE 4. Endovascular Therapy in the ICAS Group and Embolism Group ICAS group (n = 22) Embolism group (n = 39) P value Intracranial artery angioplasty  With balloon 4 (18.2%) 0 (0%) .027  With stent 3 (13.6%) 0 (0%) .080  With balloon and stent 2 (9.1%) 0 (0%) .040  Stenting after clot retrieval 5 (22.7%) 0 (0%) .009  Balloon angioplasty after clot retrieval 4 (18.2%) 0 (0%) .027  With Balloon and stent balloon plus stent 1 (4.5%) 0 (0%) .150 Mechanical thrombectomy 3 (13.6%) 39 (100%) <.001 ICAS group (n = 22) Embolism group (n = 39) P value Intracranial artery angioplasty  With balloon 4 (18.2%) 0 (0%) .027  With stent 3 (13.6%) 0 (0%) .080  With balloon and stent 2 (9.1%) 0 (0%) .040  Stenting after clot retrieval 5 (22.7%) 0 (0%) .009  Balloon angioplasty after clot retrieval 4 (18.2%) 0 (0%) .027  With Balloon and stent balloon plus stent 1 (4.5%) 0 (0%) .150 Mechanical thrombectomy 3 (13.6%) 39 (100%) <.001 View Large Diagnostic Performance of the Microcatheter First-Pass Effect The microcatheter first-pass effect was positive in 20 of the 22 patients in the ICAS group but in only 5 patients in the non-ICAS group (90.9% vs 12.8%, respectively, P < .001). Sensitivity of the microcatheter first-pass effect for the detection of ICAS was 90.9%, specificity was 87.2%, PPV was 80.0%, NPV was 94.4%, and accuracy was 88.5%. DISCUSSION To the best of our knowledge, ours is the first study to show that clinicians can apply what we refer to as the microcatheter first-pass effect during endovascular intervention to differentiate ICAS from intracranial embolism. The microcatheter first-pass effect is the temporary slow blood flow seen at the site of total occlusion when a microcatheter is advanced through the affected artery and then retrieved on the proximal side of the occlusion. The phenomenon itself was first mentioned by Lee et al,21 but they did not report that the interventionist can use it to differentiate ICAS from embolism. The microcatheter first-pass effect may result from the fact that the fresh clot burden is low in a stenotic intracranial artery;3 the clot may easily break loose. When the microcatheter is advanced through a totally occluded artery, a portion of the fresh thrombus may be pushed into the distal patent segment, where it dissolves, and a portion may adhere to the vessel wall. Thus, a channel is established, and when the microcatheter is retrieved proximal to the occlusion site, transient slow flow can be seen angiographically. Our study showed significant association between the microcatheter first-pass effect and ICAS (90.9% in the ICAS group vs 12.8% in the non-ICAS group, P < .001) with high sensitivity (90.9%), high specificity (87.2%), high PPV (80%), high NPV (94.4%), and high accuracy (88.5%). Five other factors associated with ICAS differed between our patients in whom the first-pass effect was observed and those in whom it was not. The first was the presence of arteriosclerotic risk factors, hypertension in particular. Hypertension has been associated with ICAS.11 The second was the prevalence of male sex, which corresponds to results of a study conducted by Lee et al11 that showed an increased likelihood of ICAS among male patients. The third was absence of atrial fibrillation and/or a history of rheumatoid heart disease. Atrial fibrillation and rheumatic heart disease are conditions that put patients at risk for cardiac-embolic stroke. The fourth factor was the low occurrence of the HAS on nonenhanced CT. HAS is related to many factors such as the thrombus volume, stroke subtype, and components of the thrombus.22,23 Red thrombi are usually generated in diseased heart and are rich in red cells, whereas white thrombi are usually generated in atherosclerotic intracranial vessels and are rich in platelets.22 The density of white thrombi is lower than that of red thrombi,24,25 so the HAS is predictive of cardioembolic stroke.22 Finally, the most supportive point was that atherosclerosis plaque was observed on high-resolution MR images in 9 of the 22 ICAS cases, and first-pass effect was observed in all 9 of these cases. We found no carotid T occlusion in either the microcatheter first-pass effect group or the ICAS group. It may be that the carotid T occlusion is related more to intracranial embolism and that the resulting thrombus burden is high.26,27 Thus, after the microcatheter is advanced through the site of occlusion and retrieved on the proximal side of the embolus, the artery is once again occluded by the high-burden thrombus, and the microcatheter first-pass effect is not observed. Half (11/22, 50%) of the ICAS-related sites of occlusion were within the MCA, and the second most common sites were the intracranial ICA (6/22, 27.3%) and BA (5/22, 22.7%). Although the optimal treatment for underlying ICAS in patients presenting with hyperacute stroke remains unknown, the identification of underlying ICAS before endovascular therapy may help interventionists make appropriate therapeutic decisions.19 Nineteen (86.4%) of our 22 study patients with ICAS required angioplasty for recanalization to be achieved, and this was done on an emergency basis. Therefore, we believe the neuro-interventionist can utilize this phenomenon to distinguish ICAS from embolism and then choose the most appropriate treatment. Platelets play an important role in rethrombosis in patients with ICAS, and antiplatelet therapy can be applied to inhibit re-occlusion.12,13 Once the microcatheter first-pass effect is observed, the probability of ICAS-related occlusion is high. We can administer tirofiban, which is a fast-acting, fast-deactivated, highly selective, non-peptide platelet membrane glycoprotein IIb/IIIa receptor inhibitor.28 It is important to note that the clots in our ICAS patients were refractory to mechanical retrieval, necessitating emergency angioplasty. After diagnosing ICAS based on the first-pass effect, we can minimize the passage of a stent retriever, which can damage the arterial wall.29 Additionally, limited passage of the stent retriever can minimize the procedure time, which factors into a good prognosis.9 Our findings must be interpreted in light of the fact that they are based on single-center study. We also note that it might be difficult to differentiate underlying stenosis from residual emboli angiographically in patients who have undergone mechanical thrombectomy. CTA or MRA performed after the endovascular procedure in our patients with embolism showed that the responsible artery was patent without stenosis, whereas high-resolution MR performed in some of the patients with ICAS showed various degrees of stenosis and arthrosclerosis plaque burden in the responsible artery. These imaging studies verified that the differentiation between ICAS and embolism in our study patients was accurate. CONCLUSION In conclusion, we found the sensitivity of the microcatheter first-pass effect to be high for the identification of ICAS. Thus, the microcatheter first-pass effect can be used in determining an appropriate treatment strategy for patients with acute stroke. Disclosure The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES 1. Wang Y , Zhao X , Liu L et al. Prevalence and outcomes of symptomatic intracranial large artery stenoses and occlusions in China: the Chinese Intracranial Atherosclerosis (CICAS) Study . Stroke . 2014 ; 45 ( 3 ): 663 - 669 . Google Scholar CrossRef Search ADS PubMed 2. Gorelick PB , Wong KS , Bae H-J , Pandey DK . Large artery intracranial occlusive disease: a large worldwide burden but a relatively neglected frontier . Stroke . 2008 ; 39 ( 8 ): 2396 - 2399 . Google Scholar CrossRef Search ADS PubMed 3. Yoon W , Kim SK , Park MS , Kim BC , Kang HK . Endovascular treatment and the outcomes of atherosclerotic intracranial stenosis in patients with hyperacute stroke . Neurosurgery . 2015 ; 76 ( 6 ): 680 - 686 . Google Scholar CrossRef Search ADS PubMed 4. Gascou G , Lobotesis K , Machi P et al. Stent retrievers in acute ischemic stroke: complications and failures during the perioperative period . AJNR Am J Neuroradiol . 2014 ; 35 ( 6 ): 734 - 740 . Google Scholar CrossRef Search ADS PubMed 5. Campbell BC V , Mitchell PJ , Kleinig TJ et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection . N Engl J Med . 2015 ; 372 ( 11 ): 1009 - 1018 . Google Scholar CrossRef Search ADS PubMed 6. Goyal M , Demchuk AM , Menon BK et al. Randomized assessment of rapid endovascular treatment of ischemic stroke . N Engl J Med . 2015 ; 372 : 1019 - 1030 . Google Scholar CrossRef Search ADS PubMed 7. Saver JL , Goyal M , Bonafe A et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke . N Engl J Med . 2015 ; 372 ( 11 ): 2285 - 2295 . Google Scholar CrossRef Search ADS PubMed 8. Jovin TG , Chamorro A , Cobo E et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke . N Engl J Med . 2015 ; 372 ( 24 ): 2296 - 2306 . Google Scholar CrossRef Search ADS PubMed 9. Berkhemer OA , Fransen PSS , Beumer D et al. A randomized trial of intraarterial treatment for acute ischemic stroke . N Engl J Med . 2015 ; 372 ( 1 ): 11 - 20 . Google Scholar CrossRef Search ADS PubMed 10. Powers WJ , Derdeyn CP , Biller J et al. American Heart Association/American Stroke Association focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: a guideline for healthcare professionals from the American Heart Association/American Stroke Association . Stroke . 2015 ; 46 ( 10 ): 3020 - 3035 . Google Scholar CrossRef Search ADS PubMed 11. Lee JS , Hong JM , Lee KS et al. Endovascular therapy of cerebral arterial occlusions: intracranial atherosclerosis vs embolism . J Stroke Cerebrovasc Dis . 2015 ; 24 ( 9 ): 2074 - 2080 . Google Scholar CrossRef Search ADS PubMed 12. Kang D-H , Kim Y-W , Hwang Y-H , Park SP , Kim YS , Baik SK . Instant reocclusion following mechanical thrombectomy of in situ thromboocclusion and the role of low-dose intra-arterial tirofiban . Cerebrovasc Dis 37 ( 5 ): 350 - 5 . doi: 10.1159/000362435 . CrossRef Search ADS PubMed 13. Heo JH , Lee KY , Kim SH , Kim DI . Immediate reocclusion following a successful thrombolysis in acute stroke: a pilot study . Neurology . 2014 ; 60 ( 10 ): 1684 - 1687 . Google Scholar CrossRef Search ADS 14. Gao F , Lo WT , Sun X , Mo DP , Ma N , Miao ZR . Combined use of mechanical thrombectomy with angioplasty and stenting for acute basilar occlusions with underlying severe intracranial vertebrobasilar stenosis: preliminary experience from a single Chinese center . AJNR Am J Neuroradiol . 2015 ; 36 ( 10 ): 1947 - 1952 . Google Scholar CrossRef Search ADS PubMed 15. Dieleman N , van der Kolk AG , Zwanenburg JJM et al. Imaging intracranial vessel wall pathology with magnetic resonance imaging: current prospects and future directions . Circulation . 2014 ; 130 ( 2 ): 192 - 201 . Google Scholar CrossRef Search ADS PubMed 16. Natori T , Sasaki M , Miyoshi M et al. Evaluating middle cerebral artery atherosclerotic lesions in acute ischemic stroke using magnetic resonance T1-weighted 3-dimensional vessel wall imaging . J Stroke Cerebrovasc Dis . 2014 ; 23 ( 4 ): 706 - 711 . Google Scholar CrossRef Search ADS PubMed 17. Park JK , Kim SH , Kim BS et al. Imaging of intracranial plaques with black-blood double inversion recovery MR imaging and CT . J Neuroimaging . 2011 ; 21 ( 2 ): e64 - 68 . Google Scholar CrossRef Search ADS PubMed 18. van der Kolk AG , Zwanenburg JJM , Denswil NP et al. Imaging the intracranial atherosclerotic vessel wall using 7T MRI: initial comparison with histopathology . AJNR Am J Neuroradiol . 2015 ; 36 ( 4 ): 694 - 701 . Google Scholar CrossRef Search ADS PubMed 19. Kim SK , Yoon W , Heo TW , Park MS , Kang HK . Negative susceptibility vessel sign and underlying intracranial atherosclerotic stenosis in acute middle cerebral artery occlusion . AJNR Am J Neuroradiol . 2105 ; 36 ( 7 ): 1266 - 1271 . Google Scholar CrossRef Search ADS 20. Zaidat OO , Yoo AJ , Khatri P et al. Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement . Stroke . 2013 ; 44 ( 9 ): 2650 - 2663 . Google Scholar CrossRef Search ADS PubMed 21. Lee JS , Hong JM , Lee KS , Suh HI , Choi JW , Kim SY . Primary stent retrieval for acute intracranial large artery occlusion due to atherosclerotic disease . J Stroke . 2016 ; 18 ( 1 ): 96 - 101 . Google Scholar CrossRef Search ADS PubMed 22. Cho KH , Kim JS , Kwon SU , Cho AH , Kang DW . Significance of susceptibility vessel sign on T2*-weighted gradient echo imaging for identification of stroke subtypes . Stroke . 2005 ; 36 ( 1 ): 2379 - 2383 . Google Scholar CrossRef Search ADS PubMed 23. Kim EY , Yoo E , Choi HY , Lee JW , Heo JH . Thrombus volume comparison between patients with and without hyperattenuated artery sign on CT . AJNR Am J Neuroradiol . 2008 ; 29 ( 2 ): 359 - 62 . doi: 10.3174/ajnr.A0800 . Google Scholar CrossRef Search ADS PubMed 24. Moftakhar P , English JD , Cooke DL et al. Density of thrombus on admission CT predicts revascularization efficacy in large vessel occlusion acute ischemic stroke . Stroke . 2013 ; 44 ( 1 ): 243 - 245 . Google Scholar CrossRef Search ADS PubMed 25. Kirchhof K , Welzel T , Mecke C , Zoubaa S , Sartor K . Differentiation of white, mixed, and red thrombi: value of CT in estimation of the prognosis of thrombolysis phantom study . Radiology . 2003 ; 228 ( 1 ): 126 - 130 . Google Scholar CrossRef Search ADS PubMed 26. Tan IYL , Demchuk AM , Hopyan J et al. CT angiography clot burden score and collateral score: correlation with clinical and radiologic outcomes in acute middle cerebral artery infarct . AJNR Am J Neuroradiol . 2009 ; 30 ( 3 ): 525 - 531 . Google Scholar CrossRef Search ADS PubMed 27. Protto S , Sillanpää N , Pienimäki J-P et al. Stent retriever thrombectomy in different thrombus locations of anterior cerebral circulation . Cardiovasc Intervent Radiol . 2016 ; 39 ( 7 ): 988 - 993 . Google Scholar CrossRef Search ADS PubMed 28. Siebler M , Hennerici MG , Schneider D et al. Safety of Tirofiban in acute ischemic stroke: the SaTIS trial . Stroke . 2011 ; 42 ( 9 ): 2388 - 2392 . Google Scholar CrossRef Search ADS PubMed 29. Gory B , Bresson D , Kessler I et al. Histopathologic evaluation of arterial wall response to 5 neurovascular mechanical thrombectomy devices in a swine model . AJNR Am J Neuroradiol . 2013 ; 34 ( 11 ): 2192 - 2198 . Google Scholar CrossRef Search ADS PubMed COMMENT The authors present a method for differentiating intracranial atherosclerotic disease (ICAS) from an intracranial embolism in the evaluation of acute ischemic stroke. Using what they describe as a “first-pass effect” whereby temporary angiographic blood flow is seen distal to an occlusion after a microcatheter is passed through the blockage and immediately retrieved. The microcatheter first-pass effect was observed more frequently in the ICAS population with an accuracy of 88.5%. The authors postulate that the white thrombus usually seen with ICAS is less dense than the red thrombus associated with a cardiogenic source and as such remains patent transiently after the microcatheter is withdrawn. A blockage that displays a positive first-pass effect is theoretically less likely to respond to mechanical thrombectomy because of the underlying disease. ICAS lesions should be treated with antiplatelet agents and angioplasty with/without stenting. Knowing the origin of the occlusion should help the interventionist tailor the treatment, which would save time and expense. Jay U. Howington Savannah, Georgia Copyright © 2018 by the Congress of Neurological Surgeons This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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NeurosurgeryOxford University Press

Published: May 22, 2018

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