Emergent intracranial occlusions causing acute ischemic stroke are often related to extracranial atherosclerotic stenosis. This study aimed to investigate the association between post-procedure intracerebral hemorrhage (ICH) and emergent extracranial artery stenting and assess their effects on clinical outcomes in patients with acute ischemic stroke.
We retrospectively analyzed patients undergoing hyperacute endovascular treatment for cervicocephalic vascular occlusion in three Korean hospitals between January 2011 and February 2016. Patients who had extracranial artery involvement and were treated from 24 hours of symptom onset to puncture were included in this study, and they were divided into the extracranial stenting (ES) and non-ES groups. Any type of petechial hemorrhages and parenchymal hematoma was defined as ICH for the current study.
In total, 76 patients were included in this study. Among them, 56 patients underwent ES, and 20 patients did not. Baseline characteristics, risk factors, laboratory data, treatment methods, successful reperfusion rates, and baseline stenotic degrees of extracranial internal carotid artery did not differ between these two groups. However, atrial fibrillation was more frequent in patients without than with ES (P=0.002), and post-procedure ICH was more frequent in patients with than without ES (P=0.035). Logistic regression models revealed that ES was independently associated with post-procedure ICH (odds ratio [OR], 7.807; 95% confidence interval [CI], 1.213–50.248; P=0.031), and ICH was independently associated with poor clinical outcomes (OR, 0.202; 95% CI, 0.054–0.759; P=0.018); however, ES itself was not associated with clinical outcomes (OR, 0.530; 95% CI, 0.117–2.395; P=0.409). Notably, ICH and ES had interaction for predicting good outcomes (P=0.041).
Post-procedure ICH was associated with ES and poor clinical outcomes. Therefore, ES should be cautiously considered in patients with hyperacute stroke.
Extracranial atherosclerosis (ECAS) is observed in about 10–20% of stroke patients and is not a rare cause of acute ischemic stroke [
Carotid artery stenting is an EVT option for patients with extracranial carotid stenosis. Cases of extracranial stenting (ES) for ECAS-related occlusion in hyperacute stroke are increasing presently; however, the relationship between ES and the prevalence of post-procedural hemorrhagic transformation (HT) remains unclear. Therefore, we investigated the association between ES and the prevalence of post-procedural HT and assessed the effect of ES on clinical outcomes in patients with hyperacute stroke.
We retrospectively analyzed patients in the Acute Stroke due to Intracranial Atherosclerotic occlusion and Neurointervention-Korean Retrospective (ASIAN-KR) registry. This registry collected data on patients (aged ≥18 years) who underwent EVT for cervicocerebral artery occlusion causing ischemic stroke at three comprehensive stroke centers in Korea between January 2011 and February 2016 [
All clinical data were de-identified and allocated study identification numbers. The protocol of data collection was approved by the Institutional Review Board of each hospital and was implemented in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments.
Premorbid and 3-month modified Rankin Scale (mRS) scores, National Institutes of Health Stroke Scale (NIHSS) scores, conventional vascular risk factors, and laboratory findings on admission were collected. A 3-month mRS score of 0 to 2 or no change compared with the premorbid mRS score was defined as a good outcome, and a 3-month mRS score of 3 to 6 or an increase compared with the premorbid mRS score was classified as a poor outcome.
The location of the initial occlusion site was determined using baseline computed tomography (CT) angiography, magnetic resonance angiography, or digital subtraction angiography. Stenotic degree of extracranial artery associated with hyperacute stroke was assessed based on the North American Symptomatic Carotid Endarterectomy Trial criteria [
Endovascular devices were selected at the discretion of neurointerventionists based on consensus within each stroke team. Contact aspiration and stent retrieval were routinely used as a frontline method. Contact aspiration is a method of a forced arterial suction thrombectomy, which uses the Penumbra system (Penumbra Inc., Alameda, CA, USA). Stent retrieval is a method of clot removal by capturing and removing the thrombus with a stent retriever, such as the Solitaire AB/FR (Medtronic, Irvine, CA, USA) or Trevo (Stryker, Kalamazoo, MI, USA). Balloon guide catheters, adjuvant local lytic infusion, intracranial or extracranial angioplasty, and/or stenting were implemented as needed.
Data are expressed as mean±standard deviations, median (interquartile ranges), or numbers (percentages). Comparative analyses of clinical characteristics and treatment outcomes were performed between the ES and non-ES (NES) groups. Differences between the groups were analyzed using χ2 tests for categorical variables, the Mann-Whitney U-test for ordinal variables, or t-tests for continuous variables. To evaluate the relation between ES and the prevalence of post-procedural ICH or further clinical outcomes, we performed multivariate logistic regression analyses with major confounders. A P of <0.05 was considered significant. Statistical analyses were performed using the SPSS statistical package (version 25.0, IBM SPSS, Armonk, NY, USA).
Among the 720 registered patients, 76 patients were eligible based on the inclusion criteria (
Comparative analyses of treatment methods and outcomes between these two groups are summarized in
As observed in
In the present study, we found that the prevalence of post-procedural ICH was relatively higher in patients who underwent emergent ES than in those who did not. Good outcomes after hyperacute extracranial artery treatment were attributable to multiple factors such as younger age, lower initial NIHSS score, successful reperfusion, and the absence of any ICH after EVT. Post-procedural ICH was related emergent extracranial artery stenting and associated with poor functional outcomes.
It is well known that EVTs such as mechanical thrombectomy are preferred to intravenous thrombolysis for intracranial large artery occlusions [
Several reasons may explain the relative high risk of ICH following ES in the current study. Many studies have suggested that hyperacute ICH after extracranial carotid artery stenting is mainly associated with abrupt cerebral hyperperfusion in the chronically hypoperfused areas [
Many studies have improved the process of EVT for intracranial large artery occlusion (LAO) in patients with acute ischemic stroke and tandem occlusion from ECAS disease. It is suggested that sufficient dilation of stenosis cervical artery is important for the successful use in stent-retrieval thrombectomy or spontaneous recanalization in cases of refractory LAO [
This study has several limitations. First, this study was a retrospective study; thus, the findings in the current study cannot be generalized. For escaping potential biases, we recruited multicenter data. Second, ICH after ES in patients with posterior circulation stroke was not well evaluated. Therefore, further studies must be implemented with a large amount of data related to extracranial vertebral artery stenting. Third, no exact data on pre- or post-stenting prevention were available; therefore, we could not exactly examine whether post-procedural ICH was related to stenting or/and antiplatelet medication during the stenting period. Therefore, further studies with a standardized dosage of antiplatelet medications before and after stenting are needed.
Emergent extracranial artery stenting has been used as a treatment option for hyperacute stroke patients with extracranial artery stenosis. This study found that ICH more frequently occurred in patients who underwent ES and was related to poor clinical outcomes in which ICH and ES had interaction. The findings indicate that ES must be cautiously considered in patients with ECAS-related acute ischemic stroke.
Flowchart of this study. ASIAN-KR, Acute Stroke due to Intracranial Atherosclerotic occlusion and Neurointervention-Korean Retrospective; ECAS, Extracranial Atherosclerosis.
Baseline characteristics of patients with emergent extracranial steno-occlusive disease
No extracranial stenting (n=20) | Extracranial stenting (n=56) | P-value | |
---|---|---|---|
Age | 67.9±7.7 | 69.1±8.8 | 0.588 |
Sex, men | 16 (80.0) | 49 (87.5) | 0.413 |
Hypertension | 13 (65.0) | 38 (67.9) | 0.815 |
Diabetes mellitus | 5 (25.0) | 21 (37.5) | 0.312 |
Dyslipidemia | 7 (35.0) | 17 (30.4) | 0.701 |
Atrial fibrillation | 7 (35.0) | 4 (7.1) | 0.002 |
Smoker | 6 (30.0) | 21 (37.5) | 0.547 |
Intracranial occlusion sites | 0.620 | ||
ICA, T-type | 11 (55.0) | 29 (51.8) | |
MCA, M1 | 7 (35.0) | 21 (37.5) | |
MCA, M2 | 0 (0.0) | 1 (1.8) | |
Vertebrobasilar artery | 2 (10.0) | 2 (3.6) | |
None, extracranial ICA only | 0 (0.0) | 3 (5.4) | |
Initial NIHSS score, median | 16 (10.5–21) | 14 (10–19) | 0.469 |
ASPECTS score, median | 7 (6–8) (n=15) | 7 (5.8–9) (n=50) | 0.534 |
Hemoglobin (g/dL) | 13.3±1.2 | 13.7±1.6 | 0.275 |
White blood cell (×109/L) | 9.8±3.2 | 9.8±3.3 | 0.958 |
Platelet (×109/L) | 253.2±111.4 | 254.7±65.2 | 0.942 |
Glucose (mg/dL) | 124.3±34.8 | 144.0±65.5 | 0.097 |
Total cholesterol (mg/dL) | 169.0±45.0 | 173.8±46.9 | 0.692 |
Low-density lipoprotein (mg/dL) | 111.5±40.4 | 108.6±43.7 | 0.792 |
High-density lipoprotein (mg/dL) | 41.4±7.8 | 41.4±10.2 | 0.994 |
Triglyceride (mg/dL) | 112.7±80.3 | 147.9±217.8 | 0.484 |
Erythrocyte sedimentation rate (mm/hr) | 19.6±20.9 | 18.6±14.3 | 0.815 |
C-reactive protein (mg/dL) | 2.0±4.3 | 1.0±2.4 | 0.316 |
Initial systolic blood pressure (mmHg) | 162.2±29.0 | 157.8±27.7 | 0.551 |
Initial diastolic blood pressure (mmHg) | 85.5±18.4 | 85.9±14.1 | 0.905 |
Values are presented as mean±standard deviation or number (%).
ICA, internal carotid artery; MCA, middle cerebral artery; NIHSS, National Institutes of Health Stroke Scale; ASPECTS, Alberta Stroke Program Early CT Score.
Comparisons of treatment methods and outcomes
No extracranial stenting (n=20) | Extracranial stenting (n=56) | P-value | |
---|---|---|---|
IV thrombolysis | 9 (45.0) | 25 (44.6) | 0.978 |
Onset to puncture time (minutes) | 448.5±351.0 | 384.1±245.8 | 0.375 |
Procedure time (minutes) | 78.1±58.7 | 78.8±41.0 | 0.948 |
Use of balloon guide catheter | 6 (30.0) | 17 (30.4) | 0.976 |
Remote aspiration with balloon guide catheter | 14 (70.0) | 36 (64.3) | 0.644 |
Stent retrieval | 6 (30.0) | 17 (30.4) | 0.976 |
Contact aspiration | 16 (80.0) | 37 (66.1) | 0.244 |
Local tirofiban infusion | 4 (20.0) | 7 (12.5) | 0.413 |
Final reperfusion success | 16 (80.0) | 48 (85.7) | 0.547 |
Post-procedure intracerebral hemorrhage | 0.160 | ||
None | 17 (85.0) | 33 (58.9) | |
Hemorrhagic infarct type 1 | 0 (0.0) | 6 (10.7) | |
Hemorrhagic infarct type 2 | 1 (5.0) | 10 (17.9) | |
Parenchymal hematoma type 1 | 0 (0.0) | 3 (5.4) | |
Parenchymal hematoma type 2 | 2 (10.0) | 4 (7.1) | |
Post-procedure subarachnoid hemorrhage | 0.646 | ||
None | 19 (95.0) | 52 (92.9) | |
Fisher grade 1 | 0 (0.0) | 1 (1.8) | |
Fisher grade 2 | 0 (0.0) | 2 (3.6) | |
Fisher grade 3 | 0 (0.0) | 0 (0.0) | |
Fisher grade 4 | 1 (5.0) | 1 (1.8) | |
Modified Rankin Scale, median | 2 (1–3) | 2 (1–4) | 0.516 |
Values are presented as mean±standard deviation or number (%).
IV, intravenous.
Risk factors of intracerebral hemorrhage after EVT
Univariate analysis |
Multivariate analysis |
||||
---|---|---|---|---|---|
No hemorrhage (n=50) | Any hemorrhage (n=26) | P-value | OR (95% CI) | P-value | |
Age | 68.7±8.2 | 68.9±9.2 | 0.944 | 1.018 (0.947–1.094) | 0.623 |
Sex, men | 42 (84.0) | 23 (88.5) | 0.600 | 1.139 (0.165–7.878) | 0.895 |
Hypertension | 33 (70.2) | 17 (68.0) | 0.846 | ||
Diabetes mellitus | 19 (40.4) | 7 (28.0) | 0.296 | 0.657 (0.149–2.896) | 0.579 |
Atrial fibrillation | 7 (14.9) | 2 (8.0) | 0.400 | ||
Smoker | 15 (31.9) | 10 (40.0) | 0.493 | ||
Dyslipidemia | 16 (34.0) | 8 (32.0) | 0.861 | ||
Prior history of TIA or stroke | 7 (14.9) | 4 (16.0) | 0.901 | 3.083 (0.402–23.658) | 0.279 |
Prior usage of antiplatelets | 12 (25.5) | 7 (28.0) | 0.821 | 1.199 (0.263–5.466) | 0.815 |
Prior usage of anticoagulants | 1 (2.1) | 1 (4.0) | 0.645 | 15.776 (0.084–2975.334) | 0.302 |
Initial NIHSS score, median | 14 (10–19.3) | 15.5 (10.8–20.3) | 0.781 | 0.999 (0.904–1.104) | 0.984 |
Intracranial occlusion location | 0.405 | ||||
ICA, T-type | 27 (54.0) | 13 (50.0) | |||
MCA, M1 | 17 (34.0) | 11 (42.3) | |||
MCA, M2 | 0 (0.0) | 1 (3.8) | |||
Vertebrobasilar artery | 3 (6.0) | 0 (0.0) | |||
None, only extracranial ICA | 3 (6.0) | 0 (0.0) | |||
ASPECTS score, median | 8 (5.5–9) (n=41) | 6 (6–8) (n=24) | 0.071 | ||
Hemoglobin (g/dL) | 13.3±1.6 | 14.1±1.2 | 0.036 | ||
White blood cell (×109/L) | 9.6±3.2 | 10.3±3.3 | 0.372 | ||
Platelet (×109/L) | 253.7±88.5 | 255.6±58.4 | 0.921 | ||
Glucose (mg/dL) | 135.2±44.4 | 145.7±81.5 | 0.545 | ||
Total cholesterol (mg/dL) | 163.4±45.0 | 190.0±44.0 | 0.016 | ||
Low-density lipoprotein (mg/dL) | 101.6±40.0 | 124.0±44.8 | 0.029 | ||
High-density lipoprotein (mg/dL) | 39.1±9.1 | 45.8±9.1 | 0.003 | ||
Triglyceride (mg/dL) | 149.0±231.3 | 118.7±68.8 | 0.517 | ||
Initial systolic blood pressure (mmHg) | 160.2±28.4 | 156.6±27.3 | 0.593 | ||
Initial diastolic blood pressure (mmHg) | 86.9±14.2 | 83.6±17.1 | 0.370 | ||
IV thrombolysis | 23 (46.0) | 11 (42.3) | 0.759 | 1.735 (0.327–9.199) | 0.518 |
Onset to puncture time (minutes) | 388.0±270.5 | 426.1±290.8 | 0.571 | 1.001 (0.998–1.004) | 0.414 |
Procedure time (minutes) | 81.1±45.6 | 73.8±46.9 | 0.512 | 0.995 (0.980–1.010) | 0.516 |
Use of balloon guide catheter | 33 (66.0) | 17 (65.4) | 0.957 | ||
Remote aspiration with balloon guide catheter | 17 (34.0) | 6 (23.1) | 0.325 | ||
Stent retrieval | 12 (24.0) | 11 (42.3) | 0.099 | ||
Contact aspiration | 35 (70.0) | 18 (69.2) | 0.945 | ||
Local tirofiban infusion | 5 (10.0) | 6 (23.1) | 0.124 | ||
Extracranial stenting | 33 (66.0) | 23 (88.5) | 0.035 | 7.807 (1.213–50.248) | 0.031 |
Successfulreperfusion | 42 (84.0) | 22 (84.6) | 0.944 | ||
Good outcomes at 3 months | 34 (68.0) | 11 (42.3) | 0.031 |
Values are presented as mean±standard deviation or number (%) unless otherwise indicated.
EVT, endovascular treatment; OR, odds ratio; CI, confidence interval; TIA, transient ischemic attack; NIHSS, National Institutes of Health Stroke Scale; ICA, internal carotid artery; MCA, middle cerebral artery; ASPECTS, Alberta Stroke Program Early CT Score; IV, intravenous.
Predicting factors associated with good clinical outcomes
Univariate analysis |
Multivariate analysis |
||||
---|---|---|---|---|---|
Poor outcomes (n=31) | Good outcomes (n=45) | P-value | OR (95% CI) | P-value | |
Age | 71.9±9.5 | 66.6±7.0 | 0.007 | 0.918 (0.848–0.993) | 0.033 |
Sex, men | 27 (87.1) | 38 (84.4) | 0.747 | 0.841 (0.162–4.353) | 0.837 |
Hypertension | 22 (71.0) | 29 (64.4) | 0.552 | ||
Diabetes mellitus | 10 (32.3) | 16 (35.6) | 0.766 | 0.687 (0.177–2.665) | 0.587 |
Atrial fibrillation | 7 (22.6) | 4 (8.9) | 0.095 | 0.216 (0.027–1.718) | 0.147 |
Smoker | 7 (22.6) | 20 (44.4) | 0.050 | ||
Dyslipidemia | 8 (25.8) | 16 (35.6) | 0.369 | ||
Premorbid mRS score, median | 0 (0–1) | 0 (0–0) | 0.635 | ||
Initial NIHSS score, median | 19 (11–22) | 14 (10–17) | 0.126 | 0.895 (0.801–0.999) | 0.049 |
Initial occlusion site | 0.453 | ||||
ICA, T-type | 15 (48.4) | 25 (55.6) | |||
MCA, M1 | 11 (35.5) | 17 (37.8) | |||
MCA, M2 | 1 (3.2) | 0 (0.0) | |||
Vertebrobasilar artery | 3 (9.7) | 1 (2.2) | |||
None, only extracranial ICA | 1 (3.2) | 2 (4.4) | |||
ASPECTS score, median | 6.5 (4.3–8.8) (n=24) | 6 (7–9) (n=41) | 0.610 | ||
Onset to puncture time (minutes) | 461.3±332.8 | 359.5±224.2 | 0.144 | 0.998 (0.996–1.000) | 0.117 |
Puncture to final time (minutes) | 89.7±55.2 | 71.0±36.9 | 0.104 | ||
Prior history of TIA or stroke | 5 (16.1) | 8 (17.8) | 0.851 | ||
Prior usage of antiplatelets | 6 (19.4) | 14 (31.1) | 0.253 | ||
Prior usage of anticoagulants | 1 (3.2) | 2 (4.4) | 0.789 | ||
Initial systolic blood pressure (mmHg) | 156.0±26.1 | 161.0±29.2 | 0.450 | ||
Initial diastolic blood pressure (mmHg) | 85.6±12.6 | 85.9±16.9 | 0.929 | ||
Hemoglobin (g/dL) | 13.4±1.6 | 13.7±1.4 | 0.354 | ||
White blood cell (×109/L) | 10.6±3.6 | 9.3±2.9 | 0.090 | ||
Platelet (×109/L) | 234.8±69.4 | 267.7±83.3 | 0.075 | ||
Glucose (mg/dL) | 143.3±73.9 | 135.7±47.7 | 0.586 | ||
Total cholesterol (mg/dL) | 174.5±46.9 | 171.1±46.1 | 0.753 | ||
Low-density lipoprotein (mg/dL) | 111.0±46.6 | 108.3±40.3 | 0.787 | ||
High-density lipoprotein (mg/dL) | 43.0±10.2 | 40.4±9.1 | 0.255 | ||
Triglyceride (mg/dL) | 152.7±286.9 | 129.1±83.3 | 0.604 | ||
IV thrombolysis | 11 (35.5) | 23 (51.1) | 0.178 | 1.059 (0.236–4.752) | 0.940 |
Use of balloon guide catheter | 17 (54.8) | 33 (73.3) | 0.095 | ||
Remote aspiration with balloon guide catheter | 7 (22.6) | 16 (35.6) | 0.226 | ||
Stent retrieval | 14 (45.2) | 9 (20.0) | 0.019 | ||
Contact aspiration | 19 (61.3) | 34 (75.6) | 0.183 | ||
Local tirofiban infusion | 4 (12.9) | 7 (15.6) | 0.747 | ||
Extracranial stenting |
23 (74.2) | 33 (73.3) | 0.933 | 0.530 (0.117–2.395) | 0.409 |
Successfulreperfusion | 23 (74.2) | 41 (91.1) | 0.047 | 13.892 (2.132–90.538) | 0.006 |
Post-procedure intracerebral hemorrhage, any type |
15 (48.4) | 11 (24.4) | 0.037 | 0.202 (0.054–0.759) | 0.018 |
Post-procedure subarachnoid hemorrhage, any type | 3 (9.7) | 2 (4.4) | 0.294 |
Values are presented as mean±standard deviation or number (%) unless otherwise indicated.
OR, odds ratio; CI, confidence interval; mRS: modified Rankin Scale; NIHSS; National Institutes of Health Stroke Scale; ICA, internal carotid artery; MCA, middle cerebral artery; ASPECTS, Alberta Stroke Program Early CT Score; TIA, transient ischemic attack; IV, intravenous.
Both variables had interaction (P=0.041).