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Impact of thrombus migration on clinical outcomes in patients with internal carotid artery occlusions and patent middle cerebral artery
Journal of the Neurological Sciences 412 (2020) 116737
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Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Impact of thrombus migration on clinical outcomes in patients with internal carotid artery occlusions and patent middle cerebral artery
T
⁎
Junpei Kogea, Shoji Matsumotob, , Ichiro Nakaharab, Akira Ishiic, Taketo Hatanoa, Yujiro Tanakad, Daisuke Kondoa, Jun-ichi Kirae, Izumi Nagataa a
Department of Neurosurgery, Kokura Memorial Hospital, Fukuoka, Japan Department of Comprehensive Strokology, Fujita Health University, Aichi, Japan c Department of Neurosurgery, Kyoto University Hospital, Kyoto, Japan d Department of Neurosurgery, Tokyo Medical University, Tokyo, Japan e Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan b
A R T I C LE I N FO
A B S T R A C T
Keywords: Acute ischemic stroke Patent middle cerebral artery Collateral middle cerebral artery flow Early neurological deterioration Internal carotid artery occlusion
Background: Patency of the middle cerebral artery (MCA) in acute ischemic stroke with internal carotid artery (ICA) occlusions is associated with less severe stroke and favorable outcomes. However, thrombus migration to distal intracranial vessels may lead to unfavorable outcomes. We investigated the influence of thrombus migration on clinical outcomes in patients with ICA occlusions and patent MCA. Materials and methods: We retrospectively analyzed patients with acute ischemic stroke compromising ICA occlusions and patent MCA who were consecutively admitted to our hospital between January 2006 and March 2016. Thrombus migration was assessed (1) by analyzing the discrepancies in arterial occlusion sites between initial imaging and follow-up imaging and (2) by analyzing how occlusion sites changed during endovascular therapy. Results: Thirty-eight patients (mean age: 74.9 years; 23 men, 15 women, median National Institutes of Health Stroke Scale score = 7.5) with ICA occlusions and patent MCA were ultimately included. We identified 10 patients (26%) with thrombus migration (spontaneous: 3; during endovascular therapy: 7). Patients with thrombus migration had higher rates of unfavorable functional outcomes (modified Rankin Scale scores 3–6 at 90 days) than those without thrombus migration (90% vs. 39%, p < .01). Multivariate analysis showed that thrombus migration was independently related to unfavorable functional outcomes (odds ratio, 42.9; 95% confidence interval, 1.5–1211.0; p = .03). Conclusion: Thrombus migration in cases of ICA occlusion with patent MCA is associated with poor prognosis. Careful monitoring is required under these conditions even if the initial clinical presentation is mild.
1. Introduction Patients with acute ischemic stroke (AIS) and occlusions of the internal carotid artery (ICA) have generally poor outcomes [1]. ICA occlusions are categorized as carotid T's, I's, or L's according to the occlusive lesions [2]. Collateral flow patterns of ICA occlusions have different variations depending on the site of the occlusion [2]. Therefore, according to the collateral status, clinical presentation of ICA
occlusions might also be quite variable, including transient ischemic stroke, minor stroke, or major stroke [2]. The presence of collateral middle cerebral artery (MCA) flow might provide robust cerebral blood flow, resulting in less severe initial stroke symptoms and favorable clinical outcomes [3,4]. Thus, the patency of the ipsilateral MCA plays a significant role in ICA occlusions. Although patients with ICA occlusions and patent MCA might initially present with mild symptoms, early neurological deterioration
Abbreviations: AIS, acute ischemic stroke; ICA, internal carotid artery; MCA, middle cerebral artery; END, early neurological deterioration; TM, thrombus migration; LVO, large vessel occlusion; MRA, magnetic resonance angiography; CTA, computed tomography angiography; DSA, digital subtraction angiography; EVT, endovascular therapy; TOF, time of flight; NIHSS, National Institutes of Health Stroke Scale; PTA, percutaneous transluminal angioplasty; TOAST, Trial of Org 10,172 in Acute Stroke Treatment; TICI, Thrombolysis in Cerebral Infarction; SICH, Symptomatic intracranial hemorrhage; mRS, modified Rankin Scale ⁎ Corresponding author at: Department of Comprehensive Strokology, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan. E-mail address: [email protected] (S. Matsumoto). https://doi.org/10.1016/j.jns.2020.116737 Received 12 November 2019; Received in revised form 18 January 2020; Accepted 14 February 2020 Available online 15 February 2020 0022-510X/ © 2020 Published by Elsevier B.V.
Journal of the Neurological Sciences 412 (2020) 116737
J. Koge, et al.
(END) is frequently observed despite the presence of collateral MCA flow [3]. Previous studies have anecdotally described neurological deterioration that results from thrombus migration (TM) to distal downstream vessels in cases of large vessel occlusion (LVO) [5,6]. Further, a recent study has described the association of TM and incomplete reperfusion by mechanical thrombectomy in MCA occlusions [7]. However, no studies have focused on the clinical significance of TM in patients with ICA occlusions. Particularly in patients with ICA occlusions and patent MCA, TM to distal intracranial vessels and subsequent interruptions of collateral MCA flow might affect clinical outcomes. Therefore, we sought to investigate the influence of TM on functional outcomes in patients with ICA occlusions and patent MCA.
Indication for EVT was also based on the patient clinical presentation, combined illnesses, and neuroimaging findings. Patients with mild neurological deficits were initially treated with medical therapy and rescue EVT was considered when END occurred. Patients with stroke onset < 4.5 h underwent intravenous thrombolysis if there were no contraindications. EVT was performed with guiding aspiration (n = 8), percutaneous transluminal angioplasty (PTA) (n = 8), carotid stents (n = 10), intraarterial thrombolysis (n = 1), Merci retrievers (n = 2), Penumbra (n = 8), and stent retrievers (n = 4) (Some patients received multiple maneuvers).
2. Materials and methods
According to published methods [8], END was defined as a ≥ 4point increase in NIHSS score and persistent neurological deterioration for at least 24 h or newly developed neurological symptoms within 7 days. Patients who died during the hospital stay were assigned a score of 42. Stroke etiology was stratified according to Trial of Org 10,172 in Acute Stroke Treatment (TOAST) criteria. Reperfusion status after EVT was assessed according to a modified Thrombolysis in Cerebral Infarction (TICI) score [9]. Successful reperfusion was defined as a modified TICI score of 2b or 3. Symptomatic intracranial hemorrhage (SICH) was defined as the development of a parenchymal hematoma within 36 h after treatment that was associated with a ≥ 4-point increase in NIHSS score from baseline [10]. Unfavorable functional outcomes were defined as modified Rankin Scale (mRS) scores between 3 and 6 at 90 days. Mortality was defined as death within 90 days after treatment.
2.4. Clinical assessment
2.1. Study population and design We retrospectively collected institutional data from consecutive patients with AIS and ICA occlusion who were admitted to our institute from January 2006 to March 2016. Patients were included if (1) they had been admitted with AIS within 7 days of. symptom onset, (2) they had undergone emergency brain magnetic resonance angiography (MRA), computed tomography angiography (CTA), or digital subtraction angiography (DSA), and (3) they had had symptomatic ICA occlusions with patent MCA. ICA occlusions were diagnosed based on MRA, CTA, or DSA. Patients with ICA occlusions due to in-stent thrombosis after elective endovascular therapy (EVT) and patients who had no follow-up angiographic imaging were excluded. Baseline characteristics, risk factors, imaging, and clinical outcomes were reviewed using patient clinical records. Our institutional review board approved this retrospective analysis.
2.5. Statistical analysis Patient demographic and outcome data are presented as mean (standard deviation), count, percentage, or median (interquartile range). Categorical variables were analyzed using a χ2 test or Fisher's exact test, as appropriate. Continuous variables were analyzed using a Student t-test or the Wilcoxon rank-sum test. Multivariable logistic regression analysis was performed to evaluate independent factors associated with unfavorable functional outcomes (mRS scores, 3–6) for variables that produced p values < .10 on the univariate analyses. A p value < .05 was considered statistically significant. All statistical analyses were performed using JMP 13.0.0 software (SAS Institute, Cary, NC, USA).
2.2. Imaging assessment and analysis MRI was performed on a 3-T or 1.5-T magnetic resonance system. All patients initially underwent brain MRI on admission without contraindications. The admission MRI protocol included fluid-attenuated inversion recovery, diffusion-weighted imaging, T2*-weighted gradient-echo imaging, and time of flight (TOF)-MRA. The follow-up angiographic imaging was either MRA, CTA, or DSA. The timing and type of follow-up angiographic imaging were determined at the discretion of the physician in charge before discharge. MRI findings were independently evaluated by two stroke neurologists (J.K. and S.M.) who were blinded to the clinical data. Patent MCA was defined as the presence of collateral flow in the MCA ipsilateral to the occluded ICA, which was confirmed by TOF-MRA, CTA, or DSA. When DSA was used, patency of the MCA was confirmed by the presence of collateral MCA flow via the external carotid artery or via the circle of Willis. Following published methods [7], we defined TM as secondarily occurring downstream migration of a thrombus, which was determined by comparing initial and follow-up imaging. TM was said to have occurred if initial imaging indicated ICA occlusion with patent MCA and follow-up angiographic imaging showed that the occlusion site had moved from the proximal ICA to between the top of the ICA and the M1 segment of the MCA (Fig. 1). TM assessment was done via MRA, CTA, or DSA. Recanalization of the occluded ICA and change of the occlusion site from the proximal ICA to between the top of the ICA and the M1 segment of the MCA during EVT were also regarded as evidence for TM (Fig. 2). TM confirmed by the first angiography during intended EVT was regarded as spontaneous TM.
3. Results 3.1. General characteristics and incidence of thrombus migration A total of 98 patients had AIS with ICA occlusions during the study period. Forty-five had ICA occlusions with patent MCA. Two patients were excluded because of stroke caused by in-stent thrombosis. Five patients were excluded because follow-up angiographic imaging was lost. Thus, 38 patients (mean age: 74.9 years; 23 men, 15 women) were included in the analyses. Collateral MCA flow was confirmed in 33. patients by MRA, in 4 by DSA, and in 1 by CTA. Eighteen patients underwent immediate EVT. Seven patients presented with END before EVT and six underwent rescue EVT. In total, END occurred in nine patients (24%). Of the 24 patients undergoing EVT, successful reperfusion was achieved in 16 (67%). We identified 10 patients (26%) with TM; 3 presented with spontaneous TM and 7 experienced TM during EVT (Fig. 3).
2.3. Endovascular treatment
3.2. Influence of thrombus migration on ICA occlusion with patent MCA
Immediate EVT was considered for patients with a NIHSS score ≥ 5 or fluctuating neurological deficit, a favorable DWI ASPECTS > 5 points, and stroke symptom onset within 8 h of symptom onset.
Table 1 shows the baseline patient characteristics and clinical outcomes according to the presence of TM. Baseline characteristics including age, sex, initial stroke severity, risk factors, and treatment did 2
Journal of the Neurological Sciences 412 (2020) 116737
J. Koge, et al.
Fig. 1. An illustrative case of neurological worsening due to spontaneous thrombus migration. (A) An 81-year-old woman with a history of atrial fibrillation presents with left hemiparesis and a baseline NIHSS scores of 3. Initial MRI-DWI shows high signal intensity in the right frontal lobe. (B) MRA shows right ICA occlusion but the presence of ipsilateral collateral MCA flow (arrow). (C) Mean transit-time map on CT perfusion shows no compromised perfusion in the right ICA territory. (D) After administration of intravenous thrombolysis, her neurological symptoms deteriorate to an NIHSS score of 21 by 5.5 h after symptom onset. Follow-up MRA shows that the occlusion site had changed to the right MCA. (E, F) Rescue endovascular therapy results in successful reperfusion 7.5 h after symptom onset. (G) Final MRI-DWI shows a large infarct in the right MCA territory and clinical outcome is poor (mRS score of 4 at 90 days). NIHSS, National Institutes of Health Stroke Scale; MRI, magnetic resonance imaging; DWI, diffusion-weighted imaging; ICA, internal carotid artery; MRA, magnetic resonance angiography; MCA, middle cerebral artery; mRS, modified Rankin Scale.
three of these patients (two patients irrespective of intravenous thrombolysis and one after intravenous thrombolysis). Of the remaining two patients with mild AIS, END occurred irrespective of TM and TM occurred during rescue EVT. Functional outcome was unfavorable in all five of the patients with mild AIS.
not significantly differ between those with and without TM, nor did the median time from initial angiographic imaging to the most recent follow-up angiographic imaging. Rates of large artery atherosclerosis (as determined by the TOAST classification) were significantly lower in patients with TM than in those without TM. Patients with TM tended to have lower rates of proximal flow control using guiding catheter during EVT (TM: 33% vs. no TM: 79%, p = .08). Additionally, TM was significantly associated with lower rates of successful reperfusion (33% vs. 87%, p = .02). Patients with TM also tended to require prolonged procedure time (210 min vs. 120 min, p = .07). Further, TM significantly correlated with END (60% vs. 11%, p < .01) and with higher rates of unfavorable functional outcome (90% vs. 39%, p < .01) (Table 1). We next investigated the predictors of unfavorable functional outcomes in the patients using a multivariate analysis. After adjusting for age, sex, initial NIHSS score and large artery atherosclerosis, TM was an independent predictor of unfavorable functional outcomes (odds ratio, 42.89 [95% confidence interval, 1.52–1211.04], p = .03) (Table 2).
4. Discussion The current study demonstrates three major findings: (1) TM in patients who had ICA occlusion and patent MCA can occur spontaneously or during EVT; (2) TM is associated with unfavorable functional outcomes; (3) TM can cause dramatic neurological deterioration even in patients with mild initial clinical presentation. Kim et al. reported that END was observed in a third of their patients with mild AIS who had ICA occlusions and patent MCA [3]. However, their study did not focus on the mechanism of END. We speculate that END in some patients with ICA occlusions and patent MCA might result from interruption of collateral MCA flow caused by TM. A large proportion of patients with LVO and mild presentation have been reported to deteriorate despite optimized medical treatment [11]. TM in patients with LVO might thus be a mechanism that underlies END in these cases. Kaesmacher et al. suggested that TM occurs spontaneously in a third of cases in which MCA occlusion is isolated, and that it was associated with lower rates of complete reperfusion and substantial neurologic improvement [7]. Our results demonstrate that TM occurred spontaneously in 10% of ICA occlusions with patent MCA. TM in cases of ICA occlusion with patent MCA might lead to dramatic neurological deterioration in patients without compromised cerebral perfusion and thus might have greater impact on clinical outcomes than TM in cases of MCA occlusion. Thus, careful observations are required in cases of ICA
3.3. Detailed characteristics of patients who experienced thrombus migration Table 3 shows the detailed characteristics of patients who experienced TM. In three patients with spontaneous TM, two experienced TM irrespective of intravenous thrombolysis and EVT and one experienced TM after intravenous thrombolysis. TM during EVT occurred in seven patients.Nine patients ultimately underwent EVT, and successful reperfusion was achieved in three. However, functional outcome was unfavorable in all three of these patients. Five patients had mild initial clinical presentation (NIHSS score of < 5) and underwent medical treatment first without immediate EVT. TM occurred spontaneously in 3
Journal of the Neurological Sciences 412 (2020) 116737
J. Koge, et al.
Fig. 2. An illustrative case of thrombus migration during endovascular therapy. (A) A 68-year-old man with a history of atrial fibrillation presents with left hemiparesis and a baseline NIHSS score of 7. Initial MRI-DWI shows high signal intensity in the right insula and temporal lobe. (B) MRA shows right ICA occlusion but the presence of ipsilateral collateral MCA flow (arrow). (C) DSA also confirms the patency of the ipsilateral MCA. (D) After guiding a catheter into the right ICA, the arterial occlusion site migrates to the ipsilateral MCA. (E) Aspiration thrombectomy using Penumbra and intraarterial thrombolysis results in partial reperfusion 3 h after groin puncture. (F) Final MRI-DWI shows a large infarct in the right MCA territory, but clinical outcome is relatively good (mRS score 1 at 90 days). NIHSS, National Institutes of Health Stroke Scale; MRI, magnetic resonance imaging; DWI, diffusion-weighted imaging; ICA, internal carotid artery; MRA, magnetic resonance angiography; DSA, digital subtraction angiography; MCA, middle cerebral artery; mRS, modified Rankin Scale.
TM during the procedure may be necessary. Although this might be achieved using proximal flow control, a larger prospective study is needed to assess the efficacy of this technique. This study has several limitations in addition to being a retrospective study with a small sample size. First, collateral MCA flow via the circle of Willis was mainly assessed using TOF-MRA. Whether ICA occlusions with collateral MCA flow via the external carotid artery or leptomeningeal anastomosis have similar clinical outcomes is unclear. Second, detailed changes in cerebral blood flow before and after TM were not investigated by perfusion imaging. Third, our results might overestimate the effect of TM during EVT on rates of unsuccessful reperfusion and clinical outcomes. A small proportion of patients were
occlusions with patent MCA, even if initial neurological symptoms are mild. The efficacy of EVT for patients who have LVO with mild clinical presentation remains unclear [12]. Recent studies have investigated the optimal management for patients with mild AIS, including best medical treatment and EVT [11,13]. However, the potential risk for TM to worsen patient neurological symptoms has not been sufficiently discussed. We found that the condition of patients with TM could deteriorate even though their neurological symptoms were mild. This suggests that the interruption of functional collateral flow might determine the nature of the outcome. When EVT is considered for patients with mild AIS and ICA occlusions with collateral MCA flow, prevention of
Fig. 3. Flow chart of the study. 4
Journal of the Neurological Sciences 412 (2020) 116737
J. Koge, et al.
Table 1 Baseline and outcome characteristics of patients with and without thrombus migration. Overall (n = 38)
Thrombus migration (n = 10)
No thrombus migration (n = 28)
P value
Patient characteristics Age, y, mean (SD) Sex, female, n (%) Initial NIHSS score, median (IQR) Onset to door (hours), median (IQR) Follow-up days from first imaging, median (IQR) Atrial fibrillation, n (%) Hypertension, n (%) Diabetes mellitus, n (%) Hyperlipidemia, n (%) Anticoagulation before onset, n, (%)
74.9 (12.9) 15 (39) 7.5 (1.8–18.5) 3.75 (1–8.88) 0 (0–2) 17 (45) 29 (76) 11 (29) 10 (26) 9 (24)
78.1 (7.3) 5 (50) 5 (2−20) 2.5 (0.75–6.75) 0 (0–0) 5 (50) 6 (60) 5 (50) 1 (10) 3 (30)
73.7 (14.3) 10 (36) 10 (1−20) 4 (1.25–11) 0 (0–2) 12 (43) 23 (82) 6 (21) 9 (32) 6 (21)
0.43 0.47 0.74 0.51 0.32 0.73 0.21 0.12 0.24 0.67
TOAST classification CE, n (%) LAA, n (%) OE, n (%) UD, n (%)
18 (47) 14 (37) 1 (2) 5 (13)
6 1 0 3
12 (43) 13 (46) 1 (4) 2 (7)
0.47 0.06 1.00 0.10
9 (24) 24 (63) 18 (47) 6 (16)
7 (25) 15 (54) 13 (46) 2 (7) n = 15 11 (79) 13 (87) 120 (61–165) 391 (166–549)
1.00 0.06 1.00 0.03
14 (61) 16 (67) 140 (77–216) 397 (169–609)
2 (20) 9 (90) 5 (50) 4 (40) n=9 3 (33) 3 (33) 210 (105–288) 447 (150–1267)
0.08 0.02 0.07 0.62
9 (24) 0 (0) 5 (1–12.75) 20 (53) 4 (11)
6 (60) 0 (0) 14 (7–38) 9 (90) 2 (20)
3 (11) 0 (0) 2.5 (1−10) 11 (39) 2 (7)
0.005 – 0.006 0.009 0.28
Treatment Intravenous thrombolysis, n (%) Total EVT, n (%) Immediate EVT, n (%) Rescue EVT, n (%) Details of the EVT procedure Proximal flow control Successful reperfusion, n (%) Procedure time (min), median (IQR) Onset to reperfusion, min, median (IQR) Clinical outcomes Early neurological deterioration, n (%) Symptomatic intracranial hemorrhage, n (%) NIHSS at discharge, median (IQR) Unfavorable functional outcome, n (%) Mortality, n (%)
(60) (10) (0) (30)
SD, standard deviation; TOAST, Trial of Org 10,172 in Acute Stroke Treatment; CE, cardioembolism; LAA, large artery atherosclerosis; OE, other etiology; UD, undetermined etiology; EVT, endovascular therapy.
5. Conclusion
treated with new thrombectomy devices that might allow rapid and high rates of successful reperfusion if TM occurs during EVT. Consequently, the effect of TM during EVT might be small in the new era of mechanical thrombectomy. Fourth, patients with AIS with chronic ICA occlusion based on cervical carotid atherosclerosis might have been included in the group without TM. This situation might lead to favorable outcomes due to good collateral circulation [14].
In patients with ICA occlusions and patent MCA, TM appears to be associated with END and unfavorable clinical outcomes. Because TM is not an extremely rare phenomenon, patients with AIS who have ICA occlusions with patent MCA should be carefully observed even if the initial clinical presentation is mild. When EVT is considered for these patients, special techniques to prevent TM during EVT might be required.
Table 2 Univariate and multivariate analyses to determine predictors of unfavorable functional outcome. Univariate
Age (for 1-year increase) Female Initial NIHSS score (for 1-point increase) Onset to door (for 1-h increase) Atrial fibrillation Hypertension Diabetes mellitus Hyperlipidemia Anticoagulation before onset CE LAA UD Intravenous thrombolysis EVT Thrombus migration
Multivariate
Unadjusted OR
95% CI
P value
Adjusted OR
95% CI
P value
1.10 7.50 1.09 1.00 2.44 0.47 1.11 0.28 2.14 3.00 0.20 4.25 0.65 3.00 13.91
1.01–1.20 1.63–34.59 1.01–1.18 0.96–1.04 0.65–9.13 0.10–2.23 0.27–4.55 0.06–1.31 0.45–10.26 0.80–11.31 0.05–0.84 0.43–42.19 0.14–2.93 0.76–11.81 1.54–125.63
0.03 0.01 0.03 0.96 0.18 0.34 0.88 0.11 0.34 0.10 0.03 0.22 0.57 0.12 0.02
1.07 23.86 1.17
0.97–1.17 1.62–351.92 0.99–1.38
0.17 0.02 0.06
0.66
0.08–5.31
0.70
42.89
1.52–1211.04
0.03
CE, cardioembolism; LAA, large artery atherosclerosis; OE, other etiology; UD, undetermined etiology; EVT, endovascular therapy. 5
Journal of the Neurological Sciences 412 (2020) 116737
J. Koge, et al.
Table 3 Summary of demographic, radiographic, and outcome characteristics for patients who experienced thrombus migration. Case No.
Age (y), sex
Baseline NIHSS
Timing of TM
Thrombus location after migration
TOAST classification
IV-tPA
EVT
mTICI
mRS at 90 days
1 2 3 4 5 6 7 8 9 10
88, 71, 77, 67, 81, 80, 68, 84, 86, 79,
1 1 1 2 3 7 7 14 36 39
Spontaneous Spontaneous During EVT During EVT Spontaneous During EVT During EVT During EVT During EVT During EVT
MCA MCA MCA MCA MCA MCA MCA MCA MCA, ACA MCA
UD LAA CE CE CE CE CE UD CE UD
No No No No Yes No No No No Yes
No RE RE RE RE IE IE IE IE IE
– 2A 3 0 2B 0 2A 0 2B 0
4 5 4 6 4 4 1 4 5 6
M M F F F F M M F M
TM, thrombus migration; TOAST, Trial of Org 10,172 in Acute Stroke Treatment; Af, atrial fibrillation; IV, intravenous; tPA, tissue plasminogen activator; EVT, endovascular therapy; mTICI, modified Thrombolysis in Cerebral Infarction; CE, cardioembolism; UD, undetermined etiology; IE, immediate endovascular therapy; RE, rescue endovascular therapy; LAA, large artery atherosclerosis; ACA, anterior cerebral artery.
Funding sources
[4] M. Gliem, J.I. Lee, A. Barckhan, B. Turowski, H.P. Hartung, S. Jander, et al., Outcome and treatment effects in stroke associated with acute cervical ICA occlusion, PLoS One 12 (2017) e0170247. [5] T. Ohara, Y. Nagakane, E. Tanaka, F. Morii, T. Koizumi, Y. Yamamoto, et al., Clinical and radiological features of stroke patients with poor outcomes who do not receive intravenous thrombolysis because of mild symptoms, Eur. Neurol. 69 (2013) 4–7. [6] J.H. Yoon, Y.S. Shin, Y.C. Lim, H.S. Kim, H.S. Nam, J.H. Heo, et al., Distal migration of thrombus during intra-arterial thrombolysis, Eur. Neurol. 63 (2010) 62–63. [7] J. Kaesmacher, C. Maegerlein, M. Kaesmacher, C. Zimmer, H. Poppert, B. Friedrich, et al., Thrombus migration in the middle cerebral artery: incidence, imaging signs, and impact on success of endovascular thrombectomy, J. Am. Heart Assoc. 6 (2017) e005149. [8] A. Ois, J.E. Martinez-Rodriguez, E. Munteis, M. Gomis, A. Rodríguez-Campello, J. Jimenez-Conde, et al., Steno-occlusive arterial disease and early neurological deterioration in acute ischemic stroke, Cerebrovasc. Dis. 25 (2008) 151–156. [9] O.O. Zaidat, A.J. Yoo, P. Khatri, T.A. Tomsick, R. von Kummer, J.L. Saver, et al., Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement, Stroke 44 (2013) 2650–2663. [10] N. Wahlgren, N. Ahmed, A. Dávalos, G.A. Ford, M. Grond, W. Hacke, et al., Thrombolysis with alteplase for acute ischaemic stroke in the safe implementation of thrombolysis in stroke-monitoring study (SITS-MOST): an observational study, Lancet 369 (2007) 275–282. [11] D.C. Haussen, M. Bouslama, J.A. Grossberg, A. Anderson, S. Belagage, M. Frankel, et al., Too good to intervene? Thrombectomy for large vessel occlusion strokes with minimal symptoms: an intention-to-treat analysis, J. Neurointerv Surg. 9 (2017) 917–921. [12] M. Goyal, B.K. Menon, W.H. van Zwam, D.W. Dippel, P.J. Mitchell, A.M. Demuchuk, et al., Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials, Lancet 387 (2016) 1723–1731. [13] C. Dargazanli, C. Arquizan, B. Gory, A. Consoli, J. Labreuche, H. Redjem, et al., Mechanical thrombectomy for minor and mild stroke patients harboring large vessel occlusion in the anterior circulation: a multicenter cohort study, Stroke 48 (2017) 3274–3281. [14] V. Guglielmi, N.E. LeCouffe, S.M. Zinkstok, K.C.J. Compagne, R. Eker, K.M. Treumiet, Collateral circulation and outcome in atherosclerotic versus cardioembolic cerebral large vessel occlusion, Stroke 50 (2019) 3360–3368.
This study was supported by a Grant-in-Aid for Scientific Research (C) (16 K10727). Declaration of Competing Interest Akira Ishii has received lecturing fees from Medtronic. Jun-ichi Kira is supported by grants from JSPS KAKENHI (Grant No.16H02657) and Health and Labor Sciences Research Grants on Intractable Diseases (H29-Nanchitou (Nan)-Ippan-043), and received consultant fees, speaking fees and/or honoraria from Novartis Pharma, Mitsubishi Tanabe Pharma, Boehringer Ingelheim, Teijin Pharma, Takeda Pharmaceutical Company, Otuka Pharmaceutical, Astellas Pharma, Pfizer Japan, Eisai. The other authors have no conflicts to report. Acknowledgments We thank Adam Philips, PhD from Edanz Group (www. edanzediting.com/ac) for editing a draft of this manuscript. References [1] M. Paciaroni, V. Caso, M. Venti, P. Milla, L.J. Kappelle, G. Silvestrelli, et al., Outcome in patients with stroke associated with internal carotid artery occlusion, Cerebrovasc. Dis. 20 (2005) 108–113. [2] D.S. Liebeskind, A.C. Flint, R.F. Budzik, B. Xiang, W.S. Smith, G.R. Duckwiler, et al., Carotid I's, L's and T's: collaterals shape the outcome of intracranial carotid occlusion in acute ischemic stroke, J. Neurointerv Surg. 7 (2015) 402–407. [3] J.T. Kim, M.S. Park, K.H. Choi, T.S. Nam, S.M. Choi, K.H. Cho, et al., Clinical implications of collateral middle cerebral artery flow in acute ischaemic stroke with internal carotid artery occlusion, Eur. J. Neurol. 18 (2011) 1384–1390.
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Impact of thrombus migration on clinical outcomes in patients with internal carotid artery occlusions and patent middle cerebral artery
T
⁎
Junpei Kogea, Shoji Matsumotob, , Ichiro Nakaharab, Akira Ishiic, Taketo Hatanoa, Yujiro Tanakad, Daisuke Kondoa, Jun-ichi Kirae, Izumi Nagataa a
Department of Neurosurgery, Kokura Memorial Hospital, Fukuoka, Japan Department of Comprehensive Strokology, Fujita Health University, Aichi, Japan c Department of Neurosurgery, Kyoto University Hospital, Kyoto, Japan d Department of Neurosurgery, Tokyo Medical University, Tokyo, Japan e Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan b
A R T I C LE I N FO
A B S T R A C T
Keywords: Acute ischemic stroke Patent middle cerebral artery Collateral middle cerebral artery flow Early neurological deterioration Internal carotid artery occlusion
Background: Patency of the middle cerebral artery (MCA) in acute ischemic stroke with internal carotid artery (ICA) occlusions is associated with less severe stroke and favorable outcomes. However, thrombus migration to distal intracranial vessels may lead to unfavorable outcomes. We investigated the influence of thrombus migration on clinical outcomes in patients with ICA occlusions and patent MCA. Materials and methods: We retrospectively analyzed patients with acute ischemic stroke compromising ICA occlusions and patent MCA who were consecutively admitted to our hospital between January 2006 and March 2016. Thrombus migration was assessed (1) by analyzing the discrepancies in arterial occlusion sites between initial imaging and follow-up imaging and (2) by analyzing how occlusion sites changed during endovascular therapy. Results: Thirty-eight patients (mean age: 74.9 years; 23 men, 15 women, median National Institutes of Health Stroke Scale score = 7.5) with ICA occlusions and patent MCA were ultimately included. We identified 10 patients (26%) with thrombus migration (spontaneous: 3; during endovascular therapy: 7). Patients with thrombus migration had higher rates of unfavorable functional outcomes (modified Rankin Scale scores 3–6 at 90 days) than those without thrombus migration (90% vs. 39%, p < .01). Multivariate analysis showed that thrombus migration was independently related to unfavorable functional outcomes (odds ratio, 42.9; 95% confidence interval, 1.5–1211.0; p = .03). Conclusion: Thrombus migration in cases of ICA occlusion with patent MCA is associated with poor prognosis. Careful monitoring is required under these conditions even if the initial clinical presentation is mild.
1. Introduction Patients with acute ischemic stroke (AIS) and occlusions of the internal carotid artery (ICA) have generally poor outcomes [1]. ICA occlusions are categorized as carotid T's, I's, or L's according to the occlusive lesions [2]. Collateral flow patterns of ICA occlusions have different variations depending on the site of the occlusion [2]. Therefore, according to the collateral status, clinical presentation of ICA
occlusions might also be quite variable, including transient ischemic stroke, minor stroke, or major stroke [2]. The presence of collateral middle cerebral artery (MCA) flow might provide robust cerebral blood flow, resulting in less severe initial stroke symptoms and favorable clinical outcomes [3,4]. Thus, the patency of the ipsilateral MCA plays a significant role in ICA occlusions. Although patients with ICA occlusions and patent MCA might initially present with mild symptoms, early neurological deterioration
Abbreviations: AIS, acute ischemic stroke; ICA, internal carotid artery; MCA, middle cerebral artery; END, early neurological deterioration; TM, thrombus migration; LVO, large vessel occlusion; MRA, magnetic resonance angiography; CTA, computed tomography angiography; DSA, digital subtraction angiography; EVT, endovascular therapy; TOF, time of flight; NIHSS, National Institutes of Health Stroke Scale; PTA, percutaneous transluminal angioplasty; TOAST, Trial of Org 10,172 in Acute Stroke Treatment; TICI, Thrombolysis in Cerebral Infarction; SICH, Symptomatic intracranial hemorrhage; mRS, modified Rankin Scale ⁎ Corresponding author at: Department of Comprehensive Strokology, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan. E-mail address: [email protected] (S. Matsumoto). https://doi.org/10.1016/j.jns.2020.116737 Received 12 November 2019; Received in revised form 18 January 2020; Accepted 14 February 2020 Available online 15 February 2020 0022-510X/ © 2020 Published by Elsevier B.V.
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(END) is frequently observed despite the presence of collateral MCA flow [3]. Previous studies have anecdotally described neurological deterioration that results from thrombus migration (TM) to distal downstream vessels in cases of large vessel occlusion (LVO) [5,6]. Further, a recent study has described the association of TM and incomplete reperfusion by mechanical thrombectomy in MCA occlusions [7]. However, no studies have focused on the clinical significance of TM in patients with ICA occlusions. Particularly in patients with ICA occlusions and patent MCA, TM to distal intracranial vessels and subsequent interruptions of collateral MCA flow might affect clinical outcomes. Therefore, we sought to investigate the influence of TM on functional outcomes in patients with ICA occlusions and patent MCA.
Indication for EVT was also based on the patient clinical presentation, combined illnesses, and neuroimaging findings. Patients with mild neurological deficits were initially treated with medical therapy and rescue EVT was considered when END occurred. Patients with stroke onset < 4.5 h underwent intravenous thrombolysis if there were no contraindications. EVT was performed with guiding aspiration (n = 8), percutaneous transluminal angioplasty (PTA) (n = 8), carotid stents (n = 10), intraarterial thrombolysis (n = 1), Merci retrievers (n = 2), Penumbra (n = 8), and stent retrievers (n = 4) (Some patients received multiple maneuvers).
2. Materials and methods
According to published methods [8], END was defined as a ≥ 4point increase in NIHSS score and persistent neurological deterioration for at least 24 h or newly developed neurological symptoms within 7 days. Patients who died during the hospital stay were assigned a score of 42. Stroke etiology was stratified according to Trial of Org 10,172 in Acute Stroke Treatment (TOAST) criteria. Reperfusion status after EVT was assessed according to a modified Thrombolysis in Cerebral Infarction (TICI) score [9]. Successful reperfusion was defined as a modified TICI score of 2b or 3. Symptomatic intracranial hemorrhage (SICH) was defined as the development of a parenchymal hematoma within 36 h after treatment that was associated with a ≥ 4-point increase in NIHSS score from baseline [10]. Unfavorable functional outcomes were defined as modified Rankin Scale (mRS) scores between 3 and 6 at 90 days. Mortality was defined as death within 90 days after treatment.
2.4. Clinical assessment
2.1. Study population and design We retrospectively collected institutional data from consecutive patients with AIS and ICA occlusion who were admitted to our institute from January 2006 to March 2016. Patients were included if (1) they had been admitted with AIS within 7 days of. symptom onset, (2) they had undergone emergency brain magnetic resonance angiography (MRA), computed tomography angiography (CTA), or digital subtraction angiography (DSA), and (3) they had had symptomatic ICA occlusions with patent MCA. ICA occlusions were diagnosed based on MRA, CTA, or DSA. Patients with ICA occlusions due to in-stent thrombosis after elective endovascular therapy (EVT) and patients who had no follow-up angiographic imaging were excluded. Baseline characteristics, risk factors, imaging, and clinical outcomes were reviewed using patient clinical records. Our institutional review board approved this retrospective analysis.
2.5. Statistical analysis Patient demographic and outcome data are presented as mean (standard deviation), count, percentage, or median (interquartile range). Categorical variables were analyzed using a χ2 test or Fisher's exact test, as appropriate. Continuous variables were analyzed using a Student t-test or the Wilcoxon rank-sum test. Multivariable logistic regression analysis was performed to evaluate independent factors associated with unfavorable functional outcomes (mRS scores, 3–6) for variables that produced p values < .10 on the univariate analyses. A p value < .05 was considered statistically significant. All statistical analyses were performed using JMP 13.0.0 software (SAS Institute, Cary, NC, USA).
2.2. Imaging assessment and analysis MRI was performed on a 3-T or 1.5-T magnetic resonance system. All patients initially underwent brain MRI on admission without contraindications. The admission MRI protocol included fluid-attenuated inversion recovery, diffusion-weighted imaging, T2*-weighted gradient-echo imaging, and time of flight (TOF)-MRA. The follow-up angiographic imaging was either MRA, CTA, or DSA. The timing and type of follow-up angiographic imaging were determined at the discretion of the physician in charge before discharge. MRI findings were independently evaluated by two stroke neurologists (J.K. and S.M.) who were blinded to the clinical data. Patent MCA was defined as the presence of collateral flow in the MCA ipsilateral to the occluded ICA, which was confirmed by TOF-MRA, CTA, or DSA. When DSA was used, patency of the MCA was confirmed by the presence of collateral MCA flow via the external carotid artery or via the circle of Willis. Following published methods [7], we defined TM as secondarily occurring downstream migration of a thrombus, which was determined by comparing initial and follow-up imaging. TM was said to have occurred if initial imaging indicated ICA occlusion with patent MCA and follow-up angiographic imaging showed that the occlusion site had moved from the proximal ICA to between the top of the ICA and the M1 segment of the MCA (Fig. 1). TM assessment was done via MRA, CTA, or DSA. Recanalization of the occluded ICA and change of the occlusion site from the proximal ICA to between the top of the ICA and the M1 segment of the MCA during EVT were also regarded as evidence for TM (Fig. 2). TM confirmed by the first angiography during intended EVT was regarded as spontaneous TM.
3. Results 3.1. General characteristics and incidence of thrombus migration A total of 98 patients had AIS with ICA occlusions during the study period. Forty-five had ICA occlusions with patent MCA. Two patients were excluded because of stroke caused by in-stent thrombosis. Five patients were excluded because follow-up angiographic imaging was lost. Thus, 38 patients (mean age: 74.9 years; 23 men, 15 women) were included in the analyses. Collateral MCA flow was confirmed in 33. patients by MRA, in 4 by DSA, and in 1 by CTA. Eighteen patients underwent immediate EVT. Seven patients presented with END before EVT and six underwent rescue EVT. In total, END occurred in nine patients (24%). Of the 24 patients undergoing EVT, successful reperfusion was achieved in 16 (67%). We identified 10 patients (26%) with TM; 3 presented with spontaneous TM and 7 experienced TM during EVT (Fig. 3).
2.3. Endovascular treatment
3.2. Influence of thrombus migration on ICA occlusion with patent MCA
Immediate EVT was considered for patients with a NIHSS score ≥ 5 or fluctuating neurological deficit, a favorable DWI ASPECTS > 5 points, and stroke symptom onset within 8 h of symptom onset.
Table 1 shows the baseline patient characteristics and clinical outcomes according to the presence of TM. Baseline characteristics including age, sex, initial stroke severity, risk factors, and treatment did 2
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Fig. 1. An illustrative case of neurological worsening due to spontaneous thrombus migration. (A) An 81-year-old woman with a history of atrial fibrillation presents with left hemiparesis and a baseline NIHSS scores of 3. Initial MRI-DWI shows high signal intensity in the right frontal lobe. (B) MRA shows right ICA occlusion but the presence of ipsilateral collateral MCA flow (arrow). (C) Mean transit-time map on CT perfusion shows no compromised perfusion in the right ICA territory. (D) After administration of intravenous thrombolysis, her neurological symptoms deteriorate to an NIHSS score of 21 by 5.5 h after symptom onset. Follow-up MRA shows that the occlusion site had changed to the right MCA. (E, F) Rescue endovascular therapy results in successful reperfusion 7.5 h after symptom onset. (G) Final MRI-DWI shows a large infarct in the right MCA territory and clinical outcome is poor (mRS score of 4 at 90 days). NIHSS, National Institutes of Health Stroke Scale; MRI, magnetic resonance imaging; DWI, diffusion-weighted imaging; ICA, internal carotid artery; MRA, magnetic resonance angiography; MCA, middle cerebral artery; mRS, modified Rankin Scale.
three of these patients (two patients irrespective of intravenous thrombolysis and one after intravenous thrombolysis). Of the remaining two patients with mild AIS, END occurred irrespective of TM and TM occurred during rescue EVT. Functional outcome was unfavorable in all five of the patients with mild AIS.
not significantly differ between those with and without TM, nor did the median time from initial angiographic imaging to the most recent follow-up angiographic imaging. Rates of large artery atherosclerosis (as determined by the TOAST classification) were significantly lower in patients with TM than in those without TM. Patients with TM tended to have lower rates of proximal flow control using guiding catheter during EVT (TM: 33% vs. no TM: 79%, p = .08). Additionally, TM was significantly associated with lower rates of successful reperfusion (33% vs. 87%, p = .02). Patients with TM also tended to require prolonged procedure time (210 min vs. 120 min, p = .07). Further, TM significantly correlated with END (60% vs. 11%, p < .01) and with higher rates of unfavorable functional outcome (90% vs. 39%, p < .01) (Table 1). We next investigated the predictors of unfavorable functional outcomes in the patients using a multivariate analysis. After adjusting for age, sex, initial NIHSS score and large artery atherosclerosis, TM was an independent predictor of unfavorable functional outcomes (odds ratio, 42.89 [95% confidence interval, 1.52–1211.04], p = .03) (Table 2).
4. Discussion The current study demonstrates three major findings: (1) TM in patients who had ICA occlusion and patent MCA can occur spontaneously or during EVT; (2) TM is associated with unfavorable functional outcomes; (3) TM can cause dramatic neurological deterioration even in patients with mild initial clinical presentation. Kim et al. reported that END was observed in a third of their patients with mild AIS who had ICA occlusions and patent MCA [3]. However, their study did not focus on the mechanism of END. We speculate that END in some patients with ICA occlusions and patent MCA might result from interruption of collateral MCA flow caused by TM. A large proportion of patients with LVO and mild presentation have been reported to deteriorate despite optimized medical treatment [11]. TM in patients with LVO might thus be a mechanism that underlies END in these cases. Kaesmacher et al. suggested that TM occurs spontaneously in a third of cases in which MCA occlusion is isolated, and that it was associated with lower rates of complete reperfusion and substantial neurologic improvement [7]. Our results demonstrate that TM occurred spontaneously in 10% of ICA occlusions with patent MCA. TM in cases of ICA occlusion with patent MCA might lead to dramatic neurological deterioration in patients without compromised cerebral perfusion and thus might have greater impact on clinical outcomes than TM in cases of MCA occlusion. Thus, careful observations are required in cases of ICA
3.3. Detailed characteristics of patients who experienced thrombus migration Table 3 shows the detailed characteristics of patients who experienced TM. In three patients with spontaneous TM, two experienced TM irrespective of intravenous thrombolysis and EVT and one experienced TM after intravenous thrombolysis. TM during EVT occurred in seven patients.Nine patients ultimately underwent EVT, and successful reperfusion was achieved in three. However, functional outcome was unfavorable in all three of these patients. Five patients had mild initial clinical presentation (NIHSS score of < 5) and underwent medical treatment first without immediate EVT. TM occurred spontaneously in 3
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Fig. 2. An illustrative case of thrombus migration during endovascular therapy. (A) A 68-year-old man with a history of atrial fibrillation presents with left hemiparesis and a baseline NIHSS score of 7. Initial MRI-DWI shows high signal intensity in the right insula and temporal lobe. (B) MRA shows right ICA occlusion but the presence of ipsilateral collateral MCA flow (arrow). (C) DSA also confirms the patency of the ipsilateral MCA. (D) After guiding a catheter into the right ICA, the arterial occlusion site migrates to the ipsilateral MCA. (E) Aspiration thrombectomy using Penumbra and intraarterial thrombolysis results in partial reperfusion 3 h after groin puncture. (F) Final MRI-DWI shows a large infarct in the right MCA territory, but clinical outcome is relatively good (mRS score 1 at 90 days). NIHSS, National Institutes of Health Stroke Scale; MRI, magnetic resonance imaging; DWI, diffusion-weighted imaging; ICA, internal carotid artery; MRA, magnetic resonance angiography; DSA, digital subtraction angiography; MCA, middle cerebral artery; mRS, modified Rankin Scale.
TM during the procedure may be necessary. Although this might be achieved using proximal flow control, a larger prospective study is needed to assess the efficacy of this technique. This study has several limitations in addition to being a retrospective study with a small sample size. First, collateral MCA flow via the circle of Willis was mainly assessed using TOF-MRA. Whether ICA occlusions with collateral MCA flow via the external carotid artery or leptomeningeal anastomosis have similar clinical outcomes is unclear. Second, detailed changes in cerebral blood flow before and after TM were not investigated by perfusion imaging. Third, our results might overestimate the effect of TM during EVT on rates of unsuccessful reperfusion and clinical outcomes. A small proportion of patients were
occlusions with patent MCA, even if initial neurological symptoms are mild. The efficacy of EVT for patients who have LVO with mild clinical presentation remains unclear [12]. Recent studies have investigated the optimal management for patients with mild AIS, including best medical treatment and EVT [11,13]. However, the potential risk for TM to worsen patient neurological symptoms has not been sufficiently discussed. We found that the condition of patients with TM could deteriorate even though their neurological symptoms were mild. This suggests that the interruption of functional collateral flow might determine the nature of the outcome. When EVT is considered for patients with mild AIS and ICA occlusions with collateral MCA flow, prevention of
Fig. 3. Flow chart of the study. 4
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Table 1 Baseline and outcome characteristics of patients with and without thrombus migration. Overall (n = 38)
Thrombus migration (n = 10)
No thrombus migration (n = 28)
P value
Patient characteristics Age, y, mean (SD) Sex, female, n (%) Initial NIHSS score, median (IQR) Onset to door (hours), median (IQR) Follow-up days from first imaging, median (IQR) Atrial fibrillation, n (%) Hypertension, n (%) Diabetes mellitus, n (%) Hyperlipidemia, n (%) Anticoagulation before onset, n, (%)
74.9 (12.9) 15 (39) 7.5 (1.8–18.5) 3.75 (1–8.88) 0 (0–2) 17 (45) 29 (76) 11 (29) 10 (26) 9 (24)
78.1 (7.3) 5 (50) 5 (2−20) 2.5 (0.75–6.75) 0 (0–0) 5 (50) 6 (60) 5 (50) 1 (10) 3 (30)
73.7 (14.3) 10 (36) 10 (1−20) 4 (1.25–11) 0 (0–2) 12 (43) 23 (82) 6 (21) 9 (32) 6 (21)
0.43 0.47 0.74 0.51 0.32 0.73 0.21 0.12 0.24 0.67
TOAST classification CE, n (%) LAA, n (%) OE, n (%) UD, n (%)
18 (47) 14 (37) 1 (2) 5 (13)
6 1 0 3
12 (43) 13 (46) 1 (4) 2 (7)
0.47 0.06 1.00 0.10
9 (24) 24 (63) 18 (47) 6 (16)
7 (25) 15 (54) 13 (46) 2 (7) n = 15 11 (79) 13 (87) 120 (61–165) 391 (166–549)
1.00 0.06 1.00 0.03
14 (61) 16 (67) 140 (77–216) 397 (169–609)
2 (20) 9 (90) 5 (50) 4 (40) n=9 3 (33) 3 (33) 210 (105–288) 447 (150–1267)
0.08 0.02 0.07 0.62
9 (24) 0 (0) 5 (1–12.75) 20 (53) 4 (11)
6 (60) 0 (0) 14 (7–38) 9 (90) 2 (20)
3 (11) 0 (0) 2.5 (1−10) 11 (39) 2 (7)
0.005 – 0.006 0.009 0.28
Treatment Intravenous thrombolysis, n (%) Total EVT, n (%) Immediate EVT, n (%) Rescue EVT, n (%) Details of the EVT procedure Proximal flow control Successful reperfusion, n (%) Procedure time (min), median (IQR) Onset to reperfusion, min, median (IQR) Clinical outcomes Early neurological deterioration, n (%) Symptomatic intracranial hemorrhage, n (%) NIHSS at discharge, median (IQR) Unfavorable functional outcome, n (%) Mortality, n (%)
(60) (10) (0) (30)
SD, standard deviation; TOAST, Trial of Org 10,172 in Acute Stroke Treatment; CE, cardioembolism; LAA, large artery atherosclerosis; OE, other etiology; UD, undetermined etiology; EVT, endovascular therapy.
5. Conclusion
treated with new thrombectomy devices that might allow rapid and high rates of successful reperfusion if TM occurs during EVT. Consequently, the effect of TM during EVT might be small in the new era of mechanical thrombectomy. Fourth, patients with AIS with chronic ICA occlusion based on cervical carotid atherosclerosis might have been included in the group without TM. This situation might lead to favorable outcomes due to good collateral circulation [14].
In patients with ICA occlusions and patent MCA, TM appears to be associated with END and unfavorable clinical outcomes. Because TM is not an extremely rare phenomenon, patients with AIS who have ICA occlusions with patent MCA should be carefully observed even if the initial clinical presentation is mild. When EVT is considered for these patients, special techniques to prevent TM during EVT might be required.
Table 2 Univariate and multivariate analyses to determine predictors of unfavorable functional outcome. Univariate
Age (for 1-year increase) Female Initial NIHSS score (for 1-point increase) Onset to door (for 1-h increase) Atrial fibrillation Hypertension Diabetes mellitus Hyperlipidemia Anticoagulation before onset CE LAA UD Intravenous thrombolysis EVT Thrombus migration
Multivariate
Unadjusted OR
95% CI
P value
Adjusted OR
95% CI
P value
1.10 7.50 1.09 1.00 2.44 0.47 1.11 0.28 2.14 3.00 0.20 4.25 0.65 3.00 13.91
1.01–1.20 1.63–34.59 1.01–1.18 0.96–1.04 0.65–9.13 0.10–2.23 0.27–4.55 0.06–1.31 0.45–10.26 0.80–11.31 0.05–0.84 0.43–42.19 0.14–2.93 0.76–11.81 1.54–125.63
0.03 0.01 0.03 0.96 0.18 0.34 0.88 0.11 0.34 0.10 0.03 0.22 0.57 0.12 0.02
1.07 23.86 1.17
0.97–1.17 1.62–351.92 0.99–1.38
0.17 0.02 0.06
0.66
0.08–5.31
0.70
42.89
1.52–1211.04
0.03
CE, cardioembolism; LAA, large artery atherosclerosis; OE, other etiology; UD, undetermined etiology; EVT, endovascular therapy. 5
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Table 3 Summary of demographic, radiographic, and outcome characteristics for patients who experienced thrombus migration. Case No.
Age (y), sex
Baseline NIHSS
Timing of TM
Thrombus location after migration
TOAST classification
IV-tPA
EVT
mTICI
mRS at 90 days
1 2 3 4 5 6 7 8 9 10
88, 71, 77, 67, 81, 80, 68, 84, 86, 79,
1 1 1 2 3 7 7 14 36 39
Spontaneous Spontaneous During EVT During EVT Spontaneous During EVT During EVT During EVT During EVT During EVT
MCA MCA MCA MCA MCA MCA MCA MCA MCA, ACA MCA
UD LAA CE CE CE CE CE UD CE UD
No No No No Yes No No No No Yes
No RE RE RE RE IE IE IE IE IE
– 2A 3 0 2B 0 2A 0 2B 0
4 5 4 6 4 4 1 4 5 6
M M F F F F M M F M
TM, thrombus migration; TOAST, Trial of Org 10,172 in Acute Stroke Treatment; Af, atrial fibrillation; IV, intravenous; tPA, tissue plasminogen activator; EVT, endovascular therapy; mTICI, modified Thrombolysis in Cerebral Infarction; CE, cardioembolism; UD, undetermined etiology; IE, immediate endovascular therapy; RE, rescue endovascular therapy; LAA, large artery atherosclerosis; ACA, anterior cerebral artery.
Funding sources
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This study was supported by a Grant-in-Aid for Scientific Research (C) (16 K10727). Declaration of Competing Interest Akira Ishii has received lecturing fees from Medtronic. Jun-ichi Kira is supported by grants from JSPS KAKENHI (Grant No.16H02657) and Health and Labor Sciences Research Grants on Intractable Diseases (H29-Nanchitou (Nan)-Ippan-043), and received consultant fees, speaking fees and/or honoraria from Novartis Pharma, Mitsubishi Tanabe Pharma, Boehringer Ingelheim, Teijin Pharma, Takeda Pharmaceutical Company, Otuka Pharmaceutical, Astellas Pharma, Pfizer Japan, Eisai. The other authors have no conflicts to report. Acknowledgments We thank Adam Philips, PhD from Edanz Group (www. edanzediting.com/ac) for editing a draft of this manuscript. References [1] M. Paciaroni, V. Caso, M. Venti, P. Milla, L.J. Kappelle, G. Silvestrelli, et al., Outcome in patients with stroke associated with internal carotid artery occlusion, Cerebrovasc. Dis. 20 (2005) 108–113. [2] D.S. Liebeskind, A.C. Flint, R.F. Budzik, B. Xiang, W.S. Smith, G.R. Duckwiler, et al., Carotid I's, L's and T's: collaterals shape the outcome of intracranial carotid occlusion in acute ischemic stroke, J. Neurointerv Surg. 7 (2015) 402–407. [3] J.T. Kim, M.S. Park, K.H. Choi, T.S. Nam, S.M. Choi, K.H. Cho, et al., Clinical implications of collateral middle cerebral artery flow in acute ischaemic stroke with internal carotid artery occlusion, Eur. J. Neurol. 18 (2011) 1384–1390.
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