Original Paper Received: October 21, 2015 Accepted: January 12, 2016 Published online: February 17, 2016
Cerebrovasc Dis 2016;41:306–312 DOI: 10.1159/000444069
Endovascular Treatment of Acute Ischemic Stroke Due to Tandem Occlusions: Large Multicenter Series and Systematic Review Mikayel Grigoryan a, b Diogo C. Haussen a Ameer E. Hassan c Andrey Lima a Jonathan Grossberg a Leticia C. Rebello a Wondwossen Tekle c Michael Frankel a Raul G. Nogueira a
a
Department of Neurology, Marcus Stroke and Neuroscience Center, Emory University School of Medicine, and Neuroendovascular Division, Atlanta Medical Center, Tenet Healthcare, Atlanta, Ga., and c Valley Baptist Brain and Spine Network, University of Texas Health Science Center at San Antonio, Harlingen, Tex., USA
Key Words Ischemic stroke · Endovascular treatment · Tandem · Carotid occlusion
Abstract Background: Ischemic strokes due to tandem occlusions (TOs) have poor outcomes if they have been treated with only medical interventions. Recent trials demonstrated the effectiveness of endovascular treatment of acute ischemic stroke due to intracranial occlusions; however, most studies excluded patients with TOs. Methods: Retrospective review of prospectively collected thrombectomy databases from 3 stroke centers between 2011 and 2015. Consecutive patients with tandem extracranial steno-occlusive carotid disease and intracranial occlusions who underwent emergent thrombectomy were selected. Angiographic and clinical outcomes were analyzed; baseline and procedural variables were included in univariate and multivariate analyses to define the independent predictors of good outcomes (90-day modified Rankin Scale ≤2). Results: A total of 100 patients met the study inclusion criteria. The mean age was 64.4 ± 12.5, baseline National Institutes of Health Stroke Scale
© 2016 S. Karger AG, Basel 1015–9770/16/0416–0306$39.50/0 E-Mail [email protected] www.karger.com/ced
(NIHSS) 17.6 ± 5.0, time from last known well to puncture 7.3 ± 5.8 h, and Alberta Stroke Program Early CT Score (ASPECTS) 7.5 ± 1.6. Forty percent received intravenous tissue plasminogen activator. Intracranial occlusion sites included: internal carotid artery thrombus, 31%; middle cerebral artery (MCA)-M1, 53%; MCA-M2, 10%; and anterior cerebral artery, 6%. Good outcome was achieved in 42% and successful reperfusion modified thrombolysis in cerebral infarction (mTICI ≥2B) in 88% of the cases, including complete (mTICI 3) reperfusion in 40%. Severe parenchymal hematoma (PH)-2 occurred in 6% of the patients and 90-day mortality was 20%. In the multivariate analysis, younger age (OR 0.93; 95% CI 0.88–0.98; p = 0.004), lower baseline NIHSS (OR 0.84; 95% CI 0.74–0.94; p = 0.003), higher ASPECTS (OR 1.50; 95% CI 1.02–2.19; p = 0.038), and mTICI 3 reperfusion (OR 3.56; 95% CI 1.18–10.76; p = 0.024) were independent predictors of good outcome at 90 days. Conclusions: Acute endovascular treatment of tandem anterior circulation occlusions yields good outcomes and has similar outcome predictors to isolated intracranial occlusions. Given their comparable clinical behavior, these patients should be included in future trials. © 2016 S. Karger AG, Basel
Mikayel Grigoryan, MD Director of Neuroendovascular Services, Atlanta Medical Center Clinical Assistant Professor of Neurology, Georgia Health Sciences University 49 Jesse Hill Jr. Drive SE, Room #333, Atlanta, GA 30303 (USA) E-Mail mikayel @ gmail.com
Downloaded by: WMed Library 198.143.32.1 - 2/25/2016 7:22:29 PM
b
Endovascular thrombectomy (ET) has recently established itself as the standard of care in treating large-vessel anterior circulation acute ischemic stroke (AIS) patients with 5 published randomized clinical trials demonstrating its superiority over intravenous thrombolysis (IVT) [1–5]. The universal prerequisite for inclusion in these trials was the presence of an intracranial large vessel occlusion; however, most of them excluded patients with concomitant steno-occlusive disease of the extracranial circulation. Such tandem occlusions (TOs) respond poorly to IVT [6, 7], likely due to larger clot burden and limited delivery of tissue plasminogen activator (t-PA) to the intracranial occlusion, and are known to be associated with poor clinical outcomes [8, 9]. Endovascular treatment of TO is particularly complex because it is quite challenging to access the intracranial occlusion and also because of the need to address both lesions in acute settings. Various treatment strategies are utilized; however, there has been no standardized recommendation until date. Several published case series have demonstrated technical feasibility and safety of endovascular treatment of TO [10–17]. We aim to report on a large cohort of anterior circulation TO patients treated with contemporary endovascular technology and study their predictors of good clinical outcome. We also compared our outcomes with the aggregate values from published series by performing a systematic review of the literature.
Methods
tory of hypertension, dyslipidemia, atrial fibrillation, diabetes, and smoking. Procedural characteristics analyzed included the choice of anesthesia (general vs. conscious sedation), time between last known well and groin puncture, the procedure length, use of glycoprotein IIbIIIa inhibitors (GP/IIbIIIa), use of stentrievers for intracranial occlusion, use of stent for extracranial lesion, and final revascularization status using the modified thrombolysis in cerebral infarction (mTICI) scale [18]. The presence of parenchymal hematoma (PH) on the 24-hour post-procedure CT scan was noted and categorized according to the European Cooperative Acute Stroke Study criteria (PH-1 or PH-2) [19]. Good clinical outcome was pre-specified as modified Rankin Scale (mRS) score of 0–2 at 90 days. For the patients treated within 90 days of the analysis or those lost to follow-up, the discharge mRS was carried over and used for the analysis. Statistical Analysis The pooled database was examined by using univariate/multivariate techniques. Continuous variables were reported as mean ± SD, whereas categorical variables were reported as proportions. First, univariate relationship between the variables and good clinical outcome was identified using chi-square, analysis of variance, or t test where applicable. Subsequently, a multivariate logistic regression analysis was performed for variables at the p < 0.1 level of significance. Statistical analyses were performed using IBM® SPSS® Statistics 21 (IBM®, Armonk, N.Y., USA). Systematic Review and Data Extraction We searched the literature from January 1, 2007 through August 31, 2015 to identify individual studies using the PubMed (US National Library of Medicine) database. Keywords used for this search were: (‘tandem occlusion’ or ‘carotid occlusion’) and (‘endovascular treatment’) and (‘stroke’). In addition, we handsearched the references provided in the review articles on ET in stroke. All types of studies were eligible; however, we excluded those published in non-English languages.
Results
Patient Selection and Outcome Measures We performed a retrospective review of prospectively collected thrombectomy databases across three institutions for all consecutive cases of endovascular treatment of AIS between February 2011 and June 2015. Of those, we identified patients with tandem anterior circulation extracranial (due to atherosclerotic disease or dissection) and intracranial occlusions that underwent emergent endovascular treatment. All relevant patient data were combined in a single pooled dataset. The study was approved by the local Institutional Review Boards. The baseline clinical variables, procedural characteristics and imaging/clinical outcomes, which were similar in all 3 databases, were included in this analysis. The baseline variables analyzed included the following: age, gender, mean arterial pressure, baseline National Institutes of Health Stroke Scale (NIHSS), pretreatment with intravenous t-PA, baseline Alberta Stroke Program Early CT Score (ASPECTS), etiology of the extracranial steno-occlusive lesion (atherosclerosis vs. dissection), intracranial occlusion site (internal carotid artery (ICA) vs. middle cerebral artery (MCA)-M1 vs. MCA-M2 vs. anterior cerebral artery (ACA)), as well as clinical his-
Of the 952 AIS patients treated with thrombectomy across the 3 stroke centers within the study period, 100 (10.5%) patients who were included in the analysis had anterior circulation TOs. The frequencies of TO strokes were 10.2% (81/790) at Grady Memorial Hospital, 10.9% (6/55) at Atlanta Medical Center, and 12.1% (13/107) at Valley Baptist Hospital. Baseline and procedural data were available for all 100 patients; however, the 90-day mRS data were missing in 11 (11%) patients and their discharge mRS was carried over for the analysis. Table 1 outlines baseline characteristics, procedural variables, and angiographic/clinical outcomes. The mean age was 64.4 ± 12.5, mean baseline NIHSS was 17.6 ± 5.0, and mean ASPECTS was 7.5 ± 1.6. The mean time from stroke onset (or last seen well if unwitnessed onset) to puncture was 7.3 ± 5.8 h. Forty percent received IV t-PA. Intracranial occlusion sites included the ICA-T in 31%,
Endovascular Treatment of TOs
Cerebrovasc Dis 2016;41:306–312 DOI: 10.1159/000444069
307
Downloaded by: WMed Library 198.143.32.1 - 2/25/2016 7:22:29 PM
Introduction
comes TOs (n = 100) Baseline variables Age, years Male gender Hypertension Dyslipidemia Atrial fibrillation Diabetes Smoking MAP NIHSS IV tPA ASPECTS Extracranial dissection Intracranial occlusion Site ICA-T MCA-M1 MCA-M2 ACA Procedural characteristics Conscious sedation LKW-GP, h LKW-GP ≤6 h Procedure length, min Stentriever Extracranial stent GPIIb/IIIa mTICI 2B/3 mTICI 3 Outcomes mRS 0–2 at 90 days Mortality at 90 days Parenchymal hemorrhage PH-1 PH-2
64.4±12.5 64 (64) 72 (52) 49 (49) 14 (14) 24 (24) 28 (28) 99±21 17.6±5.0 40 (40) 7.5±1.6 11 (11) 31 (31) 53 (53) 10 (10) 6 (6) 74 (74) 7.3±5.8 52 (52) 101±43 71 (71) 67 (67) 49 (49) 88 (88) 40 (40) 42 (42)* 20 (20) 12 (12) 6 (6)
Values are mean ± SD or n (%). LKW-GP = Last known well-to-groin puncture. * Discharge mRS was used in 11/100 patients.
MCA-M1 in 53%, MCA-M2 in 10%; and ACA in 6% of the cases. The etiology of the extracranial steno-occlusive lesion was atherosclerosis in 89% and arterial dissection in 11% of the patients. The extracranial carotid lesion was treated with stent placement in 67% of the patients. In the remaining 33%, carotid angioplasty alone was performed acutely with or without stent placement at a later time. Approximately half of the patients (49%) received intraprocedural GP/IIbIIIa inhibitors. Stentrievers were used for intracranial thrombectomy in 71% of the patients, 308
Cerebrovasc Dis 2016;41:306–312 DOI: 10.1159/000444069
while 29% were either treated with pre-stentriever era devices (MERCI, Penumbra) or with thromboaspiration alone using the ADAPT technique [20]. Reperfusion was successful (mTICI 2B/3) in 88% of the cases and was complete (TICI 3) in 40%. Good clinical outcome (mRS ≤2) was achieved in 42% of the patients (fig. 1). Any PH was noted in 18% (PH-1: 12%; PH-2: 6%) patients. The 90-day mortality rate was 20%. Results of the univariate model for good clinical outcome predictors are summarized in table 2. Younger age, higher baseline ASPECTS and lower baseline NIHSS demonstrated statistically significant association with good outcome, as did the complete (mTICI 3) reperfusion. On the other hand, preexisting hypertension and/or atrial fibrillation were inversely associated with good outcomes. Use of conscious sedation showed a strong trend towards an association with good outcomes, but did not reach the pre-specified probability value of p < 0.1 and therefore, was not included in the multivariate model. Multivariate analysis results are summarized in table 3. Younger age (OR 0.93; 95% CI 0.88–0.98; p = 0.004) and lower baseline NIHSS (OR 0.84; 95% CI 0.74–0.94; p = 0.003) were the strongest predictors of good clinical outcome at 90 days. Higher baseline ASPECTS (OR 1.50; 95% CI 1.02–2.19; p = 0.038) and mTICI 3 reperfusion (OR 3.56; 95% CI 1.18–10.76; p = 0.024) also remained significantly associated with good outcome, whereas history of hypertension or atrial fibrillation did not independently affect good outcomes. Systematic review of published articles revealed 534 cases of acute endovascular treatment of anterior circulation TOs from 13 studies published between January 2011 and August 2015, all of which were retrospective case series [10–17, 21–25] (table 4). The overall rate of successful reperfusion (TIMI ≥2 or TICI ≥2B) in these studies was 75.1% (401/534). Good clinical outcome was achieved in 41.3% of the patients, while mortality rate was 18.9%. Symptomatic intracerebral hemorrhage (sICH) rate was 9.9%.
Discussion
This study represents one of the largest multicenter retrospective series of AIS patients with TOs treated with endovascular techniques. We have carefully analyzed the predictors of good clinical outcomes and demonstrated comparable results to those patients with isolated intracranial occlusions supporting the notion that this is not a clinically heterogeneous population and as such it should Grigoryan et al.
Downloaded by: WMed Library 198.143.32.1 - 2/25/2016 7:22:29 PM
Table 1. Baseline variables, procedural characteristics and out-
b
c
Fig. 1. a–c Case example: 68-year-old man presented with sudden right MCA syndrome, NIHSS = 19. Angiogram revealed a TO of the proximal right ICA and right M1. After successful carotid an-
gioplasty, intracranial thrombectomy with a stentriever, and subsequent carotid stenting, he was discharged home in 3 days, independent in care (mRS 1).
be included in the future endovascular trials. Our study also highlights the relatively common frequency of TO strokes, which represented 10.5% (100 out of 952) of all AIS undergoing thrombectomy over the study period. This finding is consistent with the rates of 12.7 and 15.8% reported in the ESCAPE [3] and REVASCAT [4] trials, respectively. There is no consensus among the neurointerventionalists in regards to the sequence of treating these lesions in acute settings. Many [12, 14, 15, 17, 24] have advocated the proximal-to-distal approach with carotid stenting prior to intracranial thrombectomy, while some [11] recommend intracranial revascularization first with both techniques having their variations, advantages and shortcomings. In our series, the choice of treatment strategy was at the discretion of the operator and varied with the evolution of thrombectomy techniques and available armamentarium. The systematic review of TO studies revealed an overall rate of successful reperfusion (TIMI ≥2 or TICI ≥2B) of 75.1%. In comparison, in our cohort, successful angiographic reperfusion (mTICI ≥2B) was achieved in 88% (88/100) of the cases, while complete reperfusion (mTICI grade 3 only) was noted in 40% (40/100) cases. These values are similar to those reported in the recent stentriever trials in patients with isolated intracranial occlusions
(mTICI ≥2B of 88% in SWIFT PRIME [5], 86% in EXTEND-IA [2]). Interestingly, the mTICI ≥2B was not predictive of good clinical outcome (p = 0.517) in our series likely because of its overall high frequency. However, complete reperfusion was highly associated with good outcomes (p = 0.004). The rate of good clinical outcomes in our study was 42% and was similar to that of the systematic review (41.3%) and within the range of the recent randomized trials of ET vs. medical treatment alone (33–71%) despite the later treatment times in our study (time from stroke onset to puncture: 7.3 ± 5.8 vs. 3.4–4.3 h in the recent RCTs). A very recent multicenter series from Germany (n = 170) reported a 36% rate of good outcome [20]. Another large series (n = 77) had similar outcomes to ours (90-day mRS ≤2 of 41.6%), but their patient cohort had lower mean baseline NIHSS (14.8 vs. 17.6) and higher mean ASPECTS (8.5 vs. 7.5) [12]. Both of these baseline variables were significantly associated with good outcome in our multivariate analysis (p = 0.003 and p = 0.038, respectively). Stentrievers were utilized in a majority (71%) of intracranial occlusions in our cohort (some of the cases predated their availability) but their use was not a predictor of outcome in our study. There was a strong trend towards better outcomes with the use of intraprocedural
Endovascular Treatment of TOs
Cerebrovasc Dis 2016;41:306–312 DOI: 10.1159/000444069
309
Downloaded by: WMed Library 198.143.32.1 - 2/25/2016 7:22:29 PM
a
Yes Age, years (mean) Gender Male Female Hypertension Dyslipidemia Atrial fibrillation Diabetes Smoking MAP NIHSS (mean) IV t-PA Aspects (mean) Extracranial dissection Intracranial occlusion site ICA-T MCA-M1 MCA-M2 ACA Anesthesia General Conscious sedation LKW-GP, h (mean) ≤6 >6 Procedure length, min (mean) IIbIIIa Stentriever Extracranial stent TICI 2B or 3 TICI 3 only Parenchymal hemorrhage (PH-1 and PH-2)
No
p value
59.8
67.6
0.001*
29 13 26 17 1 7 14 97.9 15.1 18 7.2 7
35 23 46 32 13 17 14 100.9 19.2 22 8.0 4
0.405
10 20 7 5
0.072* 0.162 0.004* 0.163 0.37 0.568 0.001* 0.682 0.020* 0.194
21 33 3 1
0.242
7 35 7.5 25 17 98 20 31 28 38 24
19 39 7.1 27 31 104 29 40 39 50 16
0.105
0.534 0.842 0.66 1 0.517 0.004*
6
12
0.439
0.652 0.228
* Included in the multivariate model. LKW-GP = Last known well-to-groin puncture.
Table 3. Multivariate predictors of good outcome at 90 days Variable
ОR (95% CI)
p value
Age, years Hypertension Atrial fibrillation NIHSS ASPECTS TICI3 reperfusion
0.93 (0.88–0.98) 0.84 (0.26–2.74) 0.36 (0.03–3.79) 0.84 (0.74–0.94) 1.50 (1.02–2.19) 3.56 (1.18–10.76)
0.004 NS NS 0.003 0.038 0.024
NS = Not significant.
310
Cerebrovasc Dis 2016;41:306–312 DOI: 10.1159/000444069
Table 4. Summary of previously published TO series First author, year published
Patients, TIMI ≥2 or mRS ≤2 n TICI ≥2B
Malik [12], 2011 Kwak [22], 2013 Maurer [13], 2015 Stampfl [16], 2014 Soize [25], 2014 Cohen [17], 2015 Lockau [11], 2015 Spiotta [15], 2015 Puri [14], 2015 Mishra [24], 2015 Heck [10], 2015 Lescher [23], 2015 Behme [21], 2015 Total, n (%)
77 35 43 24 11 24 37 16 28 7 23 39 170 534
58 26 33 15 8 19 27 16 20 7 17 25 130 401 (75.1)
Mortality sICH
32 18 8 22 4 1 14 9 5 7 4 4 2 5 1 13 2 0 17 7 4 8 3 2 11 4 2 7 0 2 12 9 5 14 4 4 62 32 15 221 (41.3) 101 (18.9) 53 (9.9)
conscious sedation vs. general anesthesia (47 vs. 29%, p = 0.105) in our study. These findings support several retrospective analyses, suggesting that benefits of ET may be diminished or lost with the use of general anesthesia [26– 28]. A randomized prospective trial comparing the 2 sedation methods is ongoing [29]. Many previous studies have investigated independent predictors of good outcome after intracranial thrombectomy but none of these were specifically for patients with TOs. In our multivariate analysis, younger age and lower NIHSS were the strongest predictors of good outcome after TO treatment, while higher baseline ASPECTS and mTICI 3 reperfusion have also shown significant association. Similar factors appear to play a role in the outcomes of patients in the pooled analysis of MERCI and Multi MERCI trials [30] as well as more recent stentrieverbased studies [31] and are included in various validated scores predicting stroke outcomes after ET predicting scores, such as POST (age) [32], THRIVE (age, baseline NIHSS) [33], or HIAT (age, baseline NIHSS, ASPECTS) [34]. Intracranial hemorrhages are a feared complication after ET and perhaps especially so, after TO treatment because of higher rates of periprocedural use of antiplatelets including GP/IIbIIIa inhibitors in these patients. In our systematic review, the overall rate of sICH was 9.9%. In our study, 18% patients had any PH, of which 12% were PH-1 type, and 6% were PH-2. All 6 PH-2 cases received a GP/IIbIIIa inhibitor intraprocedurally. The presence of any PH was not associated with poor clinical outcome in our series presumably due to the overall low Grigoryan et al.
Downloaded by: WMed Library 198.143.32.1 - 2/25/2016 7:22:29 PM
Table 2. Univariate analysis of good clinical outcome (mRS ≤2) predictors
number of PH-2 patients. While both PH-1 and PH-2 have an impact on short-term outcomes, previous studies have suggested that only PH-2 affects long-term outcomes [35]. Our study has important limitations owing to its retrospective design and non-standardized treatment. We, however, feel that these shortcomings do not significantly affect the main findings of the study.
Acknowledgments None.
Sources of Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Disclosure Statement
Conclusions
In conclusion, this study provides multicenter real-life experience in treatment of TOs in AIS supporting its safety and efficacy. Good clinical outcomes and similar outcome predictors in comparison to isolated intracranial occlusions support the inclusion of these patients in future endovascular trials.
The following authors report no conflicts of interest or disclosures: M.G., D.C.H., A.E.H., A.L., J.G., L.C.R., W.T., and M.F. R.G.N. has the following disclosures: Stryker Neurovascular (TREVO-2 Trial PI, DAWN Trial PI), Covidien (SWIFT and SWIFT-PRIME Steering Committee, STAR Trial Core Lab), and Penumbra (3-D Separator Trial Executive Committee).
References
Endovascular Treatment of TOs
Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, Lowerison MW, Sajobi TT, Hill MD; ESCAPE Trial Investigators: Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015; 372: 1019–1030. 4 Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, San Roman L, Serena J, Abilleira S, Ribo M, Millan M, Urra X, Cardona P, Lopez-Cancio E, Tomasello A, Castano C, Blasco J, Aja L, Dorado L, Quesada H, Rubiera M, Hernandez-Perez M, Goyal M, Demchuk AM, von Kummer R, Gallofre M, Davalos A; REVASCAT Trial Investigators: Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015;372:2296–2306. 5 Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, Albers GW, Cognard C, Cohen DJ, Hacke W, Jansen O, Jovin TG, Mattle HP, Nogueira RG, Siddiqui AH, Yavagal DR, Baxter BW, Devlin TG, Lopes DK, Reddy VK, du Mesnil de Rochemont R, Singer OC, Jahan R; SWIFT PRIME Investigators: Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015; 372:2285–2295. 6 Christou I, Felberg RA, Demchuk AM, Burgin WS, Malkoff M, Grotta JC, Alexandrov AV: Intravenous tissue plasminogen activa-
7
8
9
10
11
tor and flow improvement in acute ischemic stroke patients with internal carotid artery occlusion. J Neuroimaging 2002; 12: 119– 123. Kim YS, Garami Z, Mikulik R, Molina CA, Alexandrov AV; CLOTBUST Collaborators: Early recanalization rates and clinical outcomes in patients with tandem internal carotid artery/middle cerebral artery occlusion and isolated middle cerebral artery occlusion. Stroke 2005;36:869–871. Linfante I, Llinas RH, Selim M, Chaves C, Kumar S, Parker RA, Caplan LR, Schlaug G: Clinical and vascular outcome in internal carotid artery versus middle cerebral artery occlusions after intravenous tissue plasminogen activator. Stroke 2002;33:2066–2071. Rubiera M, Ribo M, Delgado-Mederos R, Santamarina E, Delgado P, Montaner J, Alvarez-Sabin J, Molina CA: Tandem internal carotid artery/middle cerebral artery occlusion: an independent predictor of poor outcome after systemic thrombolysis. Stroke 2006; 37: 2301–2305. Heck DV, Brown MD: Carotid stenting and intracranial thrombectomy for treatment of acute stroke due to tandem occlusions with aggressive antiplatelet therapy may be associated with a high incidence of intracranial hemorrhage. J Neurointerv Surg 2015;7:170– 175. Lockau H, Liebig T, Henning T, Neuschmelting V, Stetefeld H, Kabbasch C, Dorn F: Mechanical thrombectomy in tandem occlusion: procedural considerations and clinical results. Neuroradiology 2015; 57: 589– 598.
Cerebrovasc Dis 2016;41:306–312 DOI: 10.1159/000444069
311
Downloaded by: WMed Library 198.143.32.1 - 2/25/2016 7:22:29 PM
1 Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, Schonewille WJ, Vos JA, Nederkoorn PJ, Wermer MJ, van Walderveen MA, Staals J, Hofmeijer J, van Oostayen JA, Lycklama a Nijeholt GJ, Boiten J, Brouwer PA, Emmer BJ, de Bruijn SF, van Dijk LC, Kappelle LJ, Lo RH, van Dijk EJ, de Vries J, de Kort PL, van Rooij WJ, van den Berg JS, van Hasselt BA, Aerden LA, Dallinga RJ, Visser MC, Bot JC, Vroomen PC, Eshghi O, Schreuder TH, Heijboer RJ, Keizer K, Tielbeek AV, den Hertog HM, Gerrits DG, van den Berg-Vos RM, Karas GB, Steyerberg EW, Flach HZ, Marquering HA, Sprengers ME, Jenniskens SF, Beenen LF, van den Berg R, Koudstaal PJ, van Zwam WH, Roos YB, van der Lugt A, van Oostenbrugge RJ, Majoie CB, Dippel DW; MR CLEAN Investigators: A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015;372: 11–20. 2 Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, Yan B, Dowling RJ, Parsons MW, Oxley TJ, Wu TY, Brooks M, Simpson MA, Miteff F, Levi CR, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Priglinger M, Ang T, Scroop R, Barber PA, McGuinness B, Wijeratne T, Phan TG, Chong W, Chandra RV, Bladin CF, Badve M, Rice H, de Villiers L, Ma H, Desmond PM, Donnan GA, Davis SM; EXTEND-IA Investigators: Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015; 372:1009–1018. 3 Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D,
312
20
21
22
23
24
25
26
27
stroke. The European cooperative acute stroke study (ECASS). JAMA 1995;274:1017– 1025. Turk AS, Spiotta A, Frei D, Mocco J, Baxter B, Fiorella D, Siddiqui A, Mokin M, Dewan M, Woo H, Turner R, Hawk H, Miranpuri A, Chaudry I: Initial clinical experience with the ADAPT technique: a direct aspiration first pass technique for stroke thrombectomy. J Neurointerv Surg 2014;6:231–237. Behme D, Mpotsaris A, Zeyen P, Psychogios MN, Kowoll A, Maurer CJ, Joachimski F, Liman J, Wasser K, Kabbasch C, Berlis A, Knauth M, Liebig T, Weber W: Emergency stenting of the extracranial internal carotid artery in combination with anterior circulation thrombectomy in acute ischemic stroke: a retrospective multicenter study. AJNR Am J Neuroradiol 2015;36:2340–2345. Kwak HS, Hwang SB, Jin GY, Hippe DS, Chung GH: Predictors of functional outcome after emergency carotid artery stenting and intra-arterial thrombolysis for treatment of acute stroke associated with obstruction of the proximal internal carotid artery and tandem downstream occlusion. AJNR Am J Neuroradiol 2013;34:841–846. Lescher S, Czeppan K, Porto L, Singer OC, Berkefeld J: Acute stroke and obstruction of the extracranial carotid artery combined with intracranial tandem occlusion: results of interventional revascularization. Cardiovasc Intervent Radiol 2015;38:304–313. Mishra A, Stockley H, Goddard T, Sonwalker H, Wuppalapati S, Patankar T: Emergent extracranial internal carotid artery stenting and mechanical thrombectomy in acute ischaemic stroke. Interv Neuroradiol 2015; 21: 205–214. Soize S, Kadziolka K, Estrade L, Serre I, Barbe C, Pierot L: Outcome after mechanical thrombectomy using a stent retriever under conscious sedation: comparison between tandem and single occlusion of the anterior circulation. J Neuroradiol 2014;41:136–142. Abou-Chebl A, Yeatts SD, Yan B, Cockroft K, Goyal M, Jovin T, Khatri P, Meyers P, Spilker J, Sugg R, Wartenberg KE, Tomsick T, Broderick J, Hill MD: Impact of general anesthesia on safety and outcomes in the endovascular arm of interventional management of stroke (IMS) III trial. Stroke 2015;46: 2142–2148. Hassan AE, Chaudhry SA, Zacharatos H, Khatri R, Akbar U, Suri MF, Qureshi AI: Increased rate of aspiration pneumonia and poor discharge outcome among acute ischemic stroke patients following intubation for
Cerebrovasc Dis 2016;41:306–312 DOI: 10.1159/000444069
28
29
30
31
32
33
34
35
endovascular treatment. Neurocrit Care 2012;16:246–250. Jumaa MA, Zhang F, Ruiz-Ares G, Gelzinis T, Malik AM, Aleu A, Oakley JI, Jankowitz B, Lin R, Reddy V, Zaidi SF, Hammer MD, Wechsler LR, Horowitz M, Jovin TG: Comparison of safety and clinical and radiographic outcomes in endovascular acute stroke therapy for proximal middle cerebral artery occlusion with intubation and general anesthesia versus the nonintubated state. Stroke 2010;41:1180–1184. Schonenberger S, Mohlenbruch M, Pfaff J, Mundiyanapurath S, Kieser M, Bendszus M, Hacke W, Bosel J: Sedation vs. Intubation for endovascular stroke treatment (SIESTA) – a randomized monocentric trial. Int J Stroke 2015;10:969–978. Nogueira RG, Liebeskind DS, Sung G, Duckwiler G, Smith WS; MERCI; Multi MERCI Writing Committee: Predictors of good clinical outcomes, mortality, and successful revascularization in patients with acute ischemic stroke undergoing thrombectomy: pooled analysis of the mechanical embolus removal in cerebral ischemia (MERCI) and Multi MERCI trials. Stroke 2009;40:3777–3783. Daou B, Chalouhi N, Starke RM, Dalyai R, Hentschel K, Jabbour P, Rosenwasser R, Tjoumakaris SI: Predictors of outcome, complications, and recanalization of the solitaire device: a study of 89 cases. Neurosurgery 2015;77:355–360; discussion 360–361. Rangaraju S, Liggins JT, Aghaebrahim A, Streib C, Sun CH, Gupta R, Nogueira R, Frankel M, Mlynash M, Lansberg M, Albers G, Jadhav A, Jovin TG: Pittsburgh outcomes after stroke thrombectomy score predicts outcomes after endovascular therapy for anterior circulation large vessel occlusions. Stroke 2014;45:2298–2304. Flint AC, Xiang B, Gupta R, Nogueira RG, Lutsep HL, Jovin TG, Albers GW, Liebeskind DS, Sanossian N, Smith WS; TREVO-2 Trialists: THRIVE score predicts outcomes with a third-generation endovascular stroke treatment device in the TREVO-2 trial. Stroke 2013;44:3370–3375. Hallevi H, Barreto AD, Liebeskind DS, Morales MM, Martin-Schild SB, Abraham AT, Gadia J, Saver JL; UCLA Intra-Arterial Therapy Investigators, Grotta JC, Savitz SI: Identifying patients at high risk for poor outcome after intra-arterial therapy for acute ischemic stroke. Stroke 2009;40:1780–1785. Khatri P, Wechsler LR, Broderick JP: Intracranial hemorrhage associated with revascularization therapies. Stroke 2007;38:431–440.
Grigoryan et al.
Downloaded by: WMed Library 198.143.32.1 - 2/25/2016 7:22:29 PM
12 Malik AM, Vora NA, Lin R, Zaidi SF, Aleu A, Jankowitz BT, Jumaa MA, Reddy VK, Hammer MD, Wechsler LR, Horowitz MB, Jovin TG: Endovascular treatment of tandem extracranial/intracranial anterior circulation occlusions: preliminary single-center experience. Stroke 2011;42:1653–1657. 13 Maurer CJ, Joachimski F, Berlis A: Two in one: endovascular treatment of acute tandem occlusions in the anterior circulation. Clin Neuroradiol 2015;25:397–402. 14 Puri AS, Kuhn AL, Kwon HJ, Khan M, Hou SY, Lin E, Chueh J, van der Bom IM, Dabus G, Linfante I, Gounis MJ, Wakhloo AK: Endovascular treatment of tandem vascular occlusions in acute ischemic stroke. J Neurointerv Surg 2015;7:158–163. 15 Spiotta AM, Lena J, Vargas J, Hawk H, Turner RD, Chaudry MI, Turk AS: Proximal to distal approach in the treatment of tandem occlusions causing an acute stroke. J Neurointerv Surg 2015;7:164–169. 16 Stampfl S, Ringleb PA, Mohlenbruch M, Hametner C, Herweh C, Pham M, Bosel J, Haehnel S, Bendszus M, Rohde S: Emergency cervical internal carotid artery stenting in combination with intracranial thrombectomy in acute stroke. AJNR Am J Neuroradiol 2014; 35:741–746. 17 Cohen JE, Gomori JM, Rajz G, Itshayek E, Eichel R, Leker RR: Extracranial carotid artery stenting followed by intracranial stentbased thrombectomy for acute tandem occlusive disease. J Neurointerv Surg 2015; 7: 412– 417. 18 Zaidat OO, Yoo AJ, Khatri P, Tomsick TA, von Kummer R, Saver JL, Marks MP, Prabhakaran S, Kallmes DF, Fitzsimmons BF, Mocco J, Wardlaw JM, Barnwell SL, Jovin TG, Linfante I, Siddiqui AH, Alexander MJ, Hirsch JA, Wintermark M, Albers G, Woo HH, Heck DV, Lev M, Aviv R, Hacke W, Warach S, Broderick J, Derdeyn CP, Furlan A, Nogueira RG, Yavagal DR, Goyal M, Demchuk AM, Bendszus M, Liebeskind DS; Cerebral Angiographic Revascularization Grading (CARG) Collaborators; STIR Revascularization working group; STIR Thrombolysis in Cerebral Infarction (TICI) Task Force: Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement. Stroke 2013; 44: 2650– 2663. 19 Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, Boysen G, Bluhmki E, Hoxter G, Mahagne MH, et al: Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric
Cerebrovasc Dis 2016;41:306–312 DOI: 10.1159/000444069
Endovascular Treatment of Acute Ischemic Stroke Due to Tandem Occlusions: Large Multicenter Series and Systematic Review Mikayel Grigoryan a, b Diogo C. Haussen a Ameer E. Hassan c Andrey Lima a Jonathan Grossberg a Leticia C. Rebello a Wondwossen Tekle c Michael Frankel a Raul G. Nogueira a
a
Department of Neurology, Marcus Stroke and Neuroscience Center, Emory University School of Medicine, and Neuroendovascular Division, Atlanta Medical Center, Tenet Healthcare, Atlanta, Ga., and c Valley Baptist Brain and Spine Network, University of Texas Health Science Center at San Antonio, Harlingen, Tex., USA
Key Words Ischemic stroke · Endovascular treatment · Tandem · Carotid occlusion
Abstract Background: Ischemic strokes due to tandem occlusions (TOs) have poor outcomes if they have been treated with only medical interventions. Recent trials demonstrated the effectiveness of endovascular treatment of acute ischemic stroke due to intracranial occlusions; however, most studies excluded patients with TOs. Methods: Retrospective review of prospectively collected thrombectomy databases from 3 stroke centers between 2011 and 2015. Consecutive patients with tandem extracranial steno-occlusive carotid disease and intracranial occlusions who underwent emergent thrombectomy were selected. Angiographic and clinical outcomes were analyzed; baseline and procedural variables were included in univariate and multivariate analyses to define the independent predictors of good outcomes (90-day modified Rankin Scale ≤2). Results: A total of 100 patients met the study inclusion criteria. The mean age was 64.4 ± 12.5, baseline National Institutes of Health Stroke Scale
© 2016 S. Karger AG, Basel 1015–9770/16/0416–0306$39.50/0 E-Mail [email protected] www.karger.com/ced
(NIHSS) 17.6 ± 5.0, time from last known well to puncture 7.3 ± 5.8 h, and Alberta Stroke Program Early CT Score (ASPECTS) 7.5 ± 1.6. Forty percent received intravenous tissue plasminogen activator. Intracranial occlusion sites included: internal carotid artery thrombus, 31%; middle cerebral artery (MCA)-M1, 53%; MCA-M2, 10%; and anterior cerebral artery, 6%. Good outcome was achieved in 42% and successful reperfusion modified thrombolysis in cerebral infarction (mTICI ≥2B) in 88% of the cases, including complete (mTICI 3) reperfusion in 40%. Severe parenchymal hematoma (PH)-2 occurred in 6% of the patients and 90-day mortality was 20%. In the multivariate analysis, younger age (OR 0.93; 95% CI 0.88–0.98; p = 0.004), lower baseline NIHSS (OR 0.84; 95% CI 0.74–0.94; p = 0.003), higher ASPECTS (OR 1.50; 95% CI 1.02–2.19; p = 0.038), and mTICI 3 reperfusion (OR 3.56; 95% CI 1.18–10.76; p = 0.024) were independent predictors of good outcome at 90 days. Conclusions: Acute endovascular treatment of tandem anterior circulation occlusions yields good outcomes and has similar outcome predictors to isolated intracranial occlusions. Given their comparable clinical behavior, these patients should be included in future trials. © 2016 S. Karger AG, Basel
Mikayel Grigoryan, MD Director of Neuroendovascular Services, Atlanta Medical Center Clinical Assistant Professor of Neurology, Georgia Health Sciences University 49 Jesse Hill Jr. Drive SE, Room #333, Atlanta, GA 30303 (USA) E-Mail mikayel @ gmail.com
Downloaded by: WMed Library 198.143.32.1 - 2/25/2016 7:22:29 PM
b
Endovascular thrombectomy (ET) has recently established itself as the standard of care in treating large-vessel anterior circulation acute ischemic stroke (AIS) patients with 5 published randomized clinical trials demonstrating its superiority over intravenous thrombolysis (IVT) [1–5]. The universal prerequisite for inclusion in these trials was the presence of an intracranial large vessel occlusion; however, most of them excluded patients with concomitant steno-occlusive disease of the extracranial circulation. Such tandem occlusions (TOs) respond poorly to IVT [6, 7], likely due to larger clot burden and limited delivery of tissue plasminogen activator (t-PA) to the intracranial occlusion, and are known to be associated with poor clinical outcomes [8, 9]. Endovascular treatment of TO is particularly complex because it is quite challenging to access the intracranial occlusion and also because of the need to address both lesions in acute settings. Various treatment strategies are utilized; however, there has been no standardized recommendation until date. Several published case series have demonstrated technical feasibility and safety of endovascular treatment of TO [10–17]. We aim to report on a large cohort of anterior circulation TO patients treated with contemporary endovascular technology and study their predictors of good clinical outcome. We also compared our outcomes with the aggregate values from published series by performing a systematic review of the literature.
Methods
tory of hypertension, dyslipidemia, atrial fibrillation, diabetes, and smoking. Procedural characteristics analyzed included the choice of anesthesia (general vs. conscious sedation), time between last known well and groin puncture, the procedure length, use of glycoprotein IIbIIIa inhibitors (GP/IIbIIIa), use of stentrievers for intracranial occlusion, use of stent for extracranial lesion, and final revascularization status using the modified thrombolysis in cerebral infarction (mTICI) scale [18]. The presence of parenchymal hematoma (PH) on the 24-hour post-procedure CT scan was noted and categorized according to the European Cooperative Acute Stroke Study criteria (PH-1 or PH-2) [19]. Good clinical outcome was pre-specified as modified Rankin Scale (mRS) score of 0–2 at 90 days. For the patients treated within 90 days of the analysis or those lost to follow-up, the discharge mRS was carried over and used for the analysis. Statistical Analysis The pooled database was examined by using univariate/multivariate techniques. Continuous variables were reported as mean ± SD, whereas categorical variables were reported as proportions. First, univariate relationship between the variables and good clinical outcome was identified using chi-square, analysis of variance, or t test where applicable. Subsequently, a multivariate logistic regression analysis was performed for variables at the p < 0.1 level of significance. Statistical analyses were performed using IBM® SPSS® Statistics 21 (IBM®, Armonk, N.Y., USA). Systematic Review and Data Extraction We searched the literature from January 1, 2007 through August 31, 2015 to identify individual studies using the PubMed (US National Library of Medicine) database. Keywords used for this search were: (‘tandem occlusion’ or ‘carotid occlusion’) and (‘endovascular treatment’) and (‘stroke’). In addition, we handsearched the references provided in the review articles on ET in stroke. All types of studies were eligible; however, we excluded those published in non-English languages.
Results
Patient Selection and Outcome Measures We performed a retrospective review of prospectively collected thrombectomy databases across three institutions for all consecutive cases of endovascular treatment of AIS between February 2011 and June 2015. Of those, we identified patients with tandem anterior circulation extracranial (due to atherosclerotic disease or dissection) and intracranial occlusions that underwent emergent endovascular treatment. All relevant patient data were combined in a single pooled dataset. The study was approved by the local Institutional Review Boards. The baseline clinical variables, procedural characteristics and imaging/clinical outcomes, which were similar in all 3 databases, were included in this analysis. The baseline variables analyzed included the following: age, gender, mean arterial pressure, baseline National Institutes of Health Stroke Scale (NIHSS), pretreatment with intravenous t-PA, baseline Alberta Stroke Program Early CT Score (ASPECTS), etiology of the extracranial steno-occlusive lesion (atherosclerosis vs. dissection), intracranial occlusion site (internal carotid artery (ICA) vs. middle cerebral artery (MCA)-M1 vs. MCA-M2 vs. anterior cerebral artery (ACA)), as well as clinical his-
Of the 952 AIS patients treated with thrombectomy across the 3 stroke centers within the study period, 100 (10.5%) patients who were included in the analysis had anterior circulation TOs. The frequencies of TO strokes were 10.2% (81/790) at Grady Memorial Hospital, 10.9% (6/55) at Atlanta Medical Center, and 12.1% (13/107) at Valley Baptist Hospital. Baseline and procedural data were available for all 100 patients; however, the 90-day mRS data were missing in 11 (11%) patients and their discharge mRS was carried over for the analysis. Table 1 outlines baseline characteristics, procedural variables, and angiographic/clinical outcomes. The mean age was 64.4 ± 12.5, mean baseline NIHSS was 17.6 ± 5.0, and mean ASPECTS was 7.5 ± 1.6. The mean time from stroke onset (or last seen well if unwitnessed onset) to puncture was 7.3 ± 5.8 h. Forty percent received IV t-PA. Intracranial occlusion sites included the ICA-T in 31%,
Endovascular Treatment of TOs
Cerebrovasc Dis 2016;41:306–312 DOI: 10.1159/000444069
307
Downloaded by: WMed Library 198.143.32.1 - 2/25/2016 7:22:29 PM
Introduction
comes TOs (n = 100) Baseline variables Age, years Male gender Hypertension Dyslipidemia Atrial fibrillation Diabetes Smoking MAP NIHSS IV tPA ASPECTS Extracranial dissection Intracranial occlusion Site ICA-T MCA-M1 MCA-M2 ACA Procedural characteristics Conscious sedation LKW-GP, h LKW-GP ≤6 h Procedure length, min Stentriever Extracranial stent GPIIb/IIIa mTICI 2B/3 mTICI 3 Outcomes mRS 0–2 at 90 days Mortality at 90 days Parenchymal hemorrhage PH-1 PH-2
64.4±12.5 64 (64) 72 (52) 49 (49) 14 (14) 24 (24) 28 (28) 99±21 17.6±5.0 40 (40) 7.5±1.6 11 (11) 31 (31) 53 (53) 10 (10) 6 (6) 74 (74) 7.3±5.8 52 (52) 101±43 71 (71) 67 (67) 49 (49) 88 (88) 40 (40) 42 (42)* 20 (20) 12 (12) 6 (6)
Values are mean ± SD or n (%). LKW-GP = Last known well-to-groin puncture. * Discharge mRS was used in 11/100 patients.
MCA-M1 in 53%, MCA-M2 in 10%; and ACA in 6% of the cases. The etiology of the extracranial steno-occlusive lesion was atherosclerosis in 89% and arterial dissection in 11% of the patients. The extracranial carotid lesion was treated with stent placement in 67% of the patients. In the remaining 33%, carotid angioplasty alone was performed acutely with or without stent placement at a later time. Approximately half of the patients (49%) received intraprocedural GP/IIbIIIa inhibitors. Stentrievers were used for intracranial thrombectomy in 71% of the patients, 308
Cerebrovasc Dis 2016;41:306–312 DOI: 10.1159/000444069
while 29% were either treated with pre-stentriever era devices (MERCI, Penumbra) or with thromboaspiration alone using the ADAPT technique [20]. Reperfusion was successful (mTICI 2B/3) in 88% of the cases and was complete (TICI 3) in 40%. Good clinical outcome (mRS ≤2) was achieved in 42% of the patients (fig. 1). Any PH was noted in 18% (PH-1: 12%; PH-2: 6%) patients. The 90-day mortality rate was 20%. Results of the univariate model for good clinical outcome predictors are summarized in table 2. Younger age, higher baseline ASPECTS and lower baseline NIHSS demonstrated statistically significant association with good outcome, as did the complete (mTICI 3) reperfusion. On the other hand, preexisting hypertension and/or atrial fibrillation were inversely associated with good outcomes. Use of conscious sedation showed a strong trend towards an association with good outcomes, but did not reach the pre-specified probability value of p < 0.1 and therefore, was not included in the multivariate model. Multivariate analysis results are summarized in table 3. Younger age (OR 0.93; 95% CI 0.88–0.98; p = 0.004) and lower baseline NIHSS (OR 0.84; 95% CI 0.74–0.94; p = 0.003) were the strongest predictors of good clinical outcome at 90 days. Higher baseline ASPECTS (OR 1.50; 95% CI 1.02–2.19; p = 0.038) and mTICI 3 reperfusion (OR 3.56; 95% CI 1.18–10.76; p = 0.024) also remained significantly associated with good outcome, whereas history of hypertension or atrial fibrillation did not independently affect good outcomes. Systematic review of published articles revealed 534 cases of acute endovascular treatment of anterior circulation TOs from 13 studies published between January 2011 and August 2015, all of which were retrospective case series [10–17, 21–25] (table 4). The overall rate of successful reperfusion (TIMI ≥2 or TICI ≥2B) in these studies was 75.1% (401/534). Good clinical outcome was achieved in 41.3% of the patients, while mortality rate was 18.9%. Symptomatic intracerebral hemorrhage (sICH) rate was 9.9%.
Discussion
This study represents one of the largest multicenter retrospective series of AIS patients with TOs treated with endovascular techniques. We have carefully analyzed the predictors of good clinical outcomes and demonstrated comparable results to those patients with isolated intracranial occlusions supporting the notion that this is not a clinically heterogeneous population and as such it should Grigoryan et al.
Downloaded by: WMed Library 198.143.32.1 - 2/25/2016 7:22:29 PM
Table 1. Baseline variables, procedural characteristics and out-
b
c
Fig. 1. a–c Case example: 68-year-old man presented with sudden right MCA syndrome, NIHSS = 19. Angiogram revealed a TO of the proximal right ICA and right M1. After successful carotid an-
gioplasty, intracranial thrombectomy with a stentriever, and subsequent carotid stenting, he was discharged home in 3 days, independent in care (mRS 1).
be included in the future endovascular trials. Our study also highlights the relatively common frequency of TO strokes, which represented 10.5% (100 out of 952) of all AIS undergoing thrombectomy over the study period. This finding is consistent with the rates of 12.7 and 15.8% reported in the ESCAPE [3] and REVASCAT [4] trials, respectively. There is no consensus among the neurointerventionalists in regards to the sequence of treating these lesions in acute settings. Many [12, 14, 15, 17, 24] have advocated the proximal-to-distal approach with carotid stenting prior to intracranial thrombectomy, while some [11] recommend intracranial revascularization first with both techniques having their variations, advantages and shortcomings. In our series, the choice of treatment strategy was at the discretion of the operator and varied with the evolution of thrombectomy techniques and available armamentarium. The systematic review of TO studies revealed an overall rate of successful reperfusion (TIMI ≥2 or TICI ≥2B) of 75.1%. In comparison, in our cohort, successful angiographic reperfusion (mTICI ≥2B) was achieved in 88% (88/100) of the cases, while complete reperfusion (mTICI grade 3 only) was noted in 40% (40/100) cases. These values are similar to those reported in the recent stentriever trials in patients with isolated intracranial occlusions
(mTICI ≥2B of 88% in SWIFT PRIME [5], 86% in EXTEND-IA [2]). Interestingly, the mTICI ≥2B was not predictive of good clinical outcome (p = 0.517) in our series likely because of its overall high frequency. However, complete reperfusion was highly associated with good outcomes (p = 0.004). The rate of good clinical outcomes in our study was 42% and was similar to that of the systematic review (41.3%) and within the range of the recent randomized trials of ET vs. medical treatment alone (33–71%) despite the later treatment times in our study (time from stroke onset to puncture: 7.3 ± 5.8 vs. 3.4–4.3 h in the recent RCTs). A very recent multicenter series from Germany (n = 170) reported a 36% rate of good outcome [20]. Another large series (n = 77) had similar outcomes to ours (90-day mRS ≤2 of 41.6%), but their patient cohort had lower mean baseline NIHSS (14.8 vs. 17.6) and higher mean ASPECTS (8.5 vs. 7.5) [12]. Both of these baseline variables were significantly associated with good outcome in our multivariate analysis (p = 0.003 and p = 0.038, respectively). Stentrievers were utilized in a majority (71%) of intracranial occlusions in our cohort (some of the cases predated their availability) but their use was not a predictor of outcome in our study. There was a strong trend towards better outcomes with the use of intraprocedural
Endovascular Treatment of TOs
Cerebrovasc Dis 2016;41:306–312 DOI: 10.1159/000444069
309
Downloaded by: WMed Library 198.143.32.1 - 2/25/2016 7:22:29 PM
a
Yes Age, years (mean) Gender Male Female Hypertension Dyslipidemia Atrial fibrillation Diabetes Smoking MAP NIHSS (mean) IV t-PA Aspects (mean) Extracranial dissection Intracranial occlusion site ICA-T MCA-M1 MCA-M2 ACA Anesthesia General Conscious sedation LKW-GP, h (mean) ≤6 >6 Procedure length, min (mean) IIbIIIa Stentriever Extracranial stent TICI 2B or 3 TICI 3 only Parenchymal hemorrhage (PH-1 and PH-2)
No
p value
59.8
67.6
0.001*
29 13 26 17 1 7 14 97.9 15.1 18 7.2 7
35 23 46 32 13 17 14 100.9 19.2 22 8.0 4
0.405
10 20 7 5
0.072* 0.162 0.004* 0.163 0.37 0.568 0.001* 0.682 0.020* 0.194
21 33 3 1
0.242
7 35 7.5 25 17 98 20 31 28 38 24
19 39 7.1 27 31 104 29 40 39 50 16
0.105
0.534 0.842 0.66 1 0.517 0.004*
6
12
0.439
0.652 0.228
* Included in the multivariate model. LKW-GP = Last known well-to-groin puncture.
Table 3. Multivariate predictors of good outcome at 90 days Variable
ОR (95% CI)
p value
Age, years Hypertension Atrial fibrillation NIHSS ASPECTS TICI3 reperfusion
0.93 (0.88–0.98) 0.84 (0.26–2.74) 0.36 (0.03–3.79) 0.84 (0.74–0.94) 1.50 (1.02–2.19) 3.56 (1.18–10.76)
0.004 NS NS 0.003 0.038 0.024
NS = Not significant.
310
Cerebrovasc Dis 2016;41:306–312 DOI: 10.1159/000444069
Table 4. Summary of previously published TO series First author, year published
Patients, TIMI ≥2 or mRS ≤2 n TICI ≥2B
Malik [12], 2011 Kwak [22], 2013 Maurer [13], 2015 Stampfl [16], 2014 Soize [25], 2014 Cohen [17], 2015 Lockau [11], 2015 Spiotta [15], 2015 Puri [14], 2015 Mishra [24], 2015 Heck [10], 2015 Lescher [23], 2015 Behme [21], 2015 Total, n (%)
77 35 43 24 11 24 37 16 28 7 23 39 170 534
58 26 33 15 8 19 27 16 20 7 17 25 130 401 (75.1)
Mortality sICH
32 18 8 22 4 1 14 9 5 7 4 4 2 5 1 13 2 0 17 7 4 8 3 2 11 4 2 7 0 2 12 9 5 14 4 4 62 32 15 221 (41.3) 101 (18.9) 53 (9.9)
conscious sedation vs. general anesthesia (47 vs. 29%, p = 0.105) in our study. These findings support several retrospective analyses, suggesting that benefits of ET may be diminished or lost with the use of general anesthesia [26– 28]. A randomized prospective trial comparing the 2 sedation methods is ongoing [29]. Many previous studies have investigated independent predictors of good outcome after intracranial thrombectomy but none of these were specifically for patients with TOs. In our multivariate analysis, younger age and lower NIHSS were the strongest predictors of good outcome after TO treatment, while higher baseline ASPECTS and mTICI 3 reperfusion have also shown significant association. Similar factors appear to play a role in the outcomes of patients in the pooled analysis of MERCI and Multi MERCI trials [30] as well as more recent stentrieverbased studies [31] and are included in various validated scores predicting stroke outcomes after ET predicting scores, such as POST (age) [32], THRIVE (age, baseline NIHSS) [33], or HIAT (age, baseline NIHSS, ASPECTS) [34]. Intracranial hemorrhages are a feared complication after ET and perhaps especially so, after TO treatment because of higher rates of periprocedural use of antiplatelets including GP/IIbIIIa inhibitors in these patients. In our systematic review, the overall rate of sICH was 9.9%. In our study, 18% patients had any PH, of which 12% were PH-1 type, and 6% were PH-2. All 6 PH-2 cases received a GP/IIbIIIa inhibitor intraprocedurally. The presence of any PH was not associated with poor clinical outcome in our series presumably due to the overall low Grigoryan et al.
Downloaded by: WMed Library 198.143.32.1 - 2/25/2016 7:22:29 PM
Table 2. Univariate analysis of good clinical outcome (mRS ≤2) predictors
number of PH-2 patients. While both PH-1 and PH-2 have an impact on short-term outcomes, previous studies have suggested that only PH-2 affects long-term outcomes [35]. Our study has important limitations owing to its retrospective design and non-standardized treatment. We, however, feel that these shortcomings do not significantly affect the main findings of the study.
Acknowledgments None.
Sources of Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Disclosure Statement
Conclusions
In conclusion, this study provides multicenter real-life experience in treatment of TOs in AIS supporting its safety and efficacy. Good clinical outcomes and similar outcome predictors in comparison to isolated intracranial occlusions support the inclusion of these patients in future endovascular trials.
The following authors report no conflicts of interest or disclosures: M.G., D.C.H., A.E.H., A.L., J.G., L.C.R., W.T., and M.F. R.G.N. has the following disclosures: Stryker Neurovascular (TREVO-2 Trial PI, DAWN Trial PI), Covidien (SWIFT and SWIFT-PRIME Steering Committee, STAR Trial Core Lab), and Penumbra (3-D Separator Trial Executive Committee).
References
Endovascular Treatment of TOs
Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, Lowerison MW, Sajobi TT, Hill MD; ESCAPE Trial Investigators: Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015; 372: 1019–1030. 4 Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, San Roman L, Serena J, Abilleira S, Ribo M, Millan M, Urra X, Cardona P, Lopez-Cancio E, Tomasello A, Castano C, Blasco J, Aja L, Dorado L, Quesada H, Rubiera M, Hernandez-Perez M, Goyal M, Demchuk AM, von Kummer R, Gallofre M, Davalos A; REVASCAT Trial Investigators: Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015;372:2296–2306. 5 Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, Albers GW, Cognard C, Cohen DJ, Hacke W, Jansen O, Jovin TG, Mattle HP, Nogueira RG, Siddiqui AH, Yavagal DR, Baxter BW, Devlin TG, Lopes DK, Reddy VK, du Mesnil de Rochemont R, Singer OC, Jahan R; SWIFT PRIME Investigators: Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015; 372:2285–2295. 6 Christou I, Felberg RA, Demchuk AM, Burgin WS, Malkoff M, Grotta JC, Alexandrov AV: Intravenous tissue plasminogen activa-
7
8
9
10
11
tor and flow improvement in acute ischemic stroke patients with internal carotid artery occlusion. J Neuroimaging 2002; 12: 119– 123. Kim YS, Garami Z, Mikulik R, Molina CA, Alexandrov AV; CLOTBUST Collaborators: Early recanalization rates and clinical outcomes in patients with tandem internal carotid artery/middle cerebral artery occlusion and isolated middle cerebral artery occlusion. Stroke 2005;36:869–871. Linfante I, Llinas RH, Selim M, Chaves C, Kumar S, Parker RA, Caplan LR, Schlaug G: Clinical and vascular outcome in internal carotid artery versus middle cerebral artery occlusions after intravenous tissue plasminogen activator. Stroke 2002;33:2066–2071. Rubiera M, Ribo M, Delgado-Mederos R, Santamarina E, Delgado P, Montaner J, Alvarez-Sabin J, Molina CA: Tandem internal carotid artery/middle cerebral artery occlusion: an independent predictor of poor outcome after systemic thrombolysis. Stroke 2006; 37: 2301–2305. Heck DV, Brown MD: Carotid stenting and intracranial thrombectomy for treatment of acute stroke due to tandem occlusions with aggressive antiplatelet therapy may be associated with a high incidence of intracranial hemorrhage. J Neurointerv Surg 2015;7:170– 175. Lockau H, Liebig T, Henning T, Neuschmelting V, Stetefeld H, Kabbasch C, Dorn F: Mechanical thrombectomy in tandem occlusion: procedural considerations and clinical results. Neuroradiology 2015; 57: 589– 598.
Cerebrovasc Dis 2016;41:306–312 DOI: 10.1159/000444069
311
Downloaded by: WMed Library 198.143.32.1 - 2/25/2016 7:22:29 PM
1 Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, Schonewille WJ, Vos JA, Nederkoorn PJ, Wermer MJ, van Walderveen MA, Staals J, Hofmeijer J, van Oostayen JA, Lycklama a Nijeholt GJ, Boiten J, Brouwer PA, Emmer BJ, de Bruijn SF, van Dijk LC, Kappelle LJ, Lo RH, van Dijk EJ, de Vries J, de Kort PL, van Rooij WJ, van den Berg JS, van Hasselt BA, Aerden LA, Dallinga RJ, Visser MC, Bot JC, Vroomen PC, Eshghi O, Schreuder TH, Heijboer RJ, Keizer K, Tielbeek AV, den Hertog HM, Gerrits DG, van den Berg-Vos RM, Karas GB, Steyerberg EW, Flach HZ, Marquering HA, Sprengers ME, Jenniskens SF, Beenen LF, van den Berg R, Koudstaal PJ, van Zwam WH, Roos YB, van der Lugt A, van Oostenbrugge RJ, Majoie CB, Dippel DW; MR CLEAN Investigators: A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015;372: 11–20. 2 Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, Yan B, Dowling RJ, Parsons MW, Oxley TJ, Wu TY, Brooks M, Simpson MA, Miteff F, Levi CR, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Priglinger M, Ang T, Scroop R, Barber PA, McGuinness B, Wijeratne T, Phan TG, Chong W, Chandra RV, Bladin CF, Badve M, Rice H, de Villiers L, Ma H, Desmond PM, Donnan GA, Davis SM; EXTEND-IA Investigators: Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015; 372:1009–1018. 3 Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D,
312
20
21
22
23
24
25
26
27
stroke. The European cooperative acute stroke study (ECASS). JAMA 1995;274:1017– 1025. Turk AS, Spiotta A, Frei D, Mocco J, Baxter B, Fiorella D, Siddiqui A, Mokin M, Dewan M, Woo H, Turner R, Hawk H, Miranpuri A, Chaudry I: Initial clinical experience with the ADAPT technique: a direct aspiration first pass technique for stroke thrombectomy. J Neurointerv Surg 2014;6:231–237. Behme D, Mpotsaris A, Zeyen P, Psychogios MN, Kowoll A, Maurer CJ, Joachimski F, Liman J, Wasser K, Kabbasch C, Berlis A, Knauth M, Liebig T, Weber W: Emergency stenting of the extracranial internal carotid artery in combination with anterior circulation thrombectomy in acute ischemic stroke: a retrospective multicenter study. AJNR Am J Neuroradiol 2015;36:2340–2345. Kwak HS, Hwang SB, Jin GY, Hippe DS, Chung GH: Predictors of functional outcome after emergency carotid artery stenting and intra-arterial thrombolysis for treatment of acute stroke associated with obstruction of the proximal internal carotid artery and tandem downstream occlusion. AJNR Am J Neuroradiol 2013;34:841–846. Lescher S, Czeppan K, Porto L, Singer OC, Berkefeld J: Acute stroke and obstruction of the extracranial carotid artery combined with intracranial tandem occlusion: results of interventional revascularization. Cardiovasc Intervent Radiol 2015;38:304–313. Mishra A, Stockley H, Goddard T, Sonwalker H, Wuppalapati S, Patankar T: Emergent extracranial internal carotid artery stenting and mechanical thrombectomy in acute ischaemic stroke. Interv Neuroradiol 2015; 21: 205–214. Soize S, Kadziolka K, Estrade L, Serre I, Barbe C, Pierot L: Outcome after mechanical thrombectomy using a stent retriever under conscious sedation: comparison between tandem and single occlusion of the anterior circulation. J Neuroradiol 2014;41:136–142. Abou-Chebl A, Yeatts SD, Yan B, Cockroft K, Goyal M, Jovin T, Khatri P, Meyers P, Spilker J, Sugg R, Wartenberg KE, Tomsick T, Broderick J, Hill MD: Impact of general anesthesia on safety and outcomes in the endovascular arm of interventional management of stroke (IMS) III trial. Stroke 2015;46: 2142–2148. Hassan AE, Chaudhry SA, Zacharatos H, Khatri R, Akbar U, Suri MF, Qureshi AI: Increased rate of aspiration pneumonia and poor discharge outcome among acute ischemic stroke patients following intubation for
Cerebrovasc Dis 2016;41:306–312 DOI: 10.1159/000444069
28
29
30
31
32
33
34
35
endovascular treatment. Neurocrit Care 2012;16:246–250. Jumaa MA, Zhang F, Ruiz-Ares G, Gelzinis T, Malik AM, Aleu A, Oakley JI, Jankowitz B, Lin R, Reddy V, Zaidi SF, Hammer MD, Wechsler LR, Horowitz M, Jovin TG: Comparison of safety and clinical and radiographic outcomes in endovascular acute stroke therapy for proximal middle cerebral artery occlusion with intubation and general anesthesia versus the nonintubated state. Stroke 2010;41:1180–1184. Schonenberger S, Mohlenbruch M, Pfaff J, Mundiyanapurath S, Kieser M, Bendszus M, Hacke W, Bosel J: Sedation vs. Intubation for endovascular stroke treatment (SIESTA) – a randomized monocentric trial. Int J Stroke 2015;10:969–978. Nogueira RG, Liebeskind DS, Sung G, Duckwiler G, Smith WS; MERCI; Multi MERCI Writing Committee: Predictors of good clinical outcomes, mortality, and successful revascularization in patients with acute ischemic stroke undergoing thrombectomy: pooled analysis of the mechanical embolus removal in cerebral ischemia (MERCI) and Multi MERCI trials. Stroke 2009;40:3777–3783. Daou B, Chalouhi N, Starke RM, Dalyai R, Hentschel K, Jabbour P, Rosenwasser R, Tjoumakaris SI: Predictors of outcome, complications, and recanalization of the solitaire device: a study of 89 cases. Neurosurgery 2015;77:355–360; discussion 360–361. Rangaraju S, Liggins JT, Aghaebrahim A, Streib C, Sun CH, Gupta R, Nogueira R, Frankel M, Mlynash M, Lansberg M, Albers G, Jadhav A, Jovin TG: Pittsburgh outcomes after stroke thrombectomy score predicts outcomes after endovascular therapy for anterior circulation large vessel occlusions. Stroke 2014;45:2298–2304. Flint AC, Xiang B, Gupta R, Nogueira RG, Lutsep HL, Jovin TG, Albers GW, Liebeskind DS, Sanossian N, Smith WS; TREVO-2 Trialists: THRIVE score predicts outcomes with a third-generation endovascular stroke treatment device in the TREVO-2 trial. Stroke 2013;44:3370–3375. Hallevi H, Barreto AD, Liebeskind DS, Morales MM, Martin-Schild SB, Abraham AT, Gadia J, Saver JL; UCLA Intra-Arterial Therapy Investigators, Grotta JC, Savitz SI: Identifying patients at high risk for poor outcome after intra-arterial therapy for acute ischemic stroke. Stroke 2009;40:1780–1785. Khatri P, Wechsler LR, Broderick JP: Intracranial hemorrhage associated with revascularization therapies. Stroke 2007;38:431–440.
Grigoryan et al.
Downloaded by: WMed Library 198.143.32.1 - 2/25/2016 7:22:29 PM
12 Malik AM, Vora NA, Lin R, Zaidi SF, Aleu A, Jankowitz BT, Jumaa MA, Reddy VK, Hammer MD, Wechsler LR, Horowitz MB, Jovin TG: Endovascular treatment of tandem extracranial/intracranial anterior circulation occlusions: preliminary single-center experience. Stroke 2011;42:1653–1657. 13 Maurer CJ, Joachimski F, Berlis A: Two in one: endovascular treatment of acute tandem occlusions in the anterior circulation. Clin Neuroradiol 2015;25:397–402. 14 Puri AS, Kuhn AL, Kwon HJ, Khan M, Hou SY, Lin E, Chueh J, van der Bom IM, Dabus G, Linfante I, Gounis MJ, Wakhloo AK: Endovascular treatment of tandem vascular occlusions in acute ischemic stroke. J Neurointerv Surg 2015;7:158–163. 15 Spiotta AM, Lena J, Vargas J, Hawk H, Turner RD, Chaudry MI, Turk AS: Proximal to distal approach in the treatment of tandem occlusions causing an acute stroke. J Neurointerv Surg 2015;7:164–169. 16 Stampfl S, Ringleb PA, Mohlenbruch M, Hametner C, Herweh C, Pham M, Bosel J, Haehnel S, Bendszus M, Rohde S: Emergency cervical internal carotid artery stenting in combination with intracranial thrombectomy in acute stroke. AJNR Am J Neuroradiol 2014; 35:741–746. 17 Cohen JE, Gomori JM, Rajz G, Itshayek E, Eichel R, Leker RR: Extracranial carotid artery stenting followed by intracranial stentbased thrombectomy for acute tandem occlusive disease. J Neurointerv Surg 2015; 7: 412– 417. 18 Zaidat OO, Yoo AJ, Khatri P, Tomsick TA, von Kummer R, Saver JL, Marks MP, Prabhakaran S, Kallmes DF, Fitzsimmons BF, Mocco J, Wardlaw JM, Barnwell SL, Jovin TG, Linfante I, Siddiqui AH, Alexander MJ, Hirsch JA, Wintermark M, Albers G, Woo HH, Heck DV, Lev M, Aviv R, Hacke W, Warach S, Broderick J, Derdeyn CP, Furlan A, Nogueira RG, Yavagal DR, Goyal M, Demchuk AM, Bendszus M, Liebeskind DS; Cerebral Angiographic Revascularization Grading (CARG) Collaborators; STIR Revascularization working group; STIR Thrombolysis in Cerebral Infarction (TICI) Task Force: Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement. Stroke 2013; 44: 2650– 2663. 19 Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, Boysen G, Bluhmki E, Hoxter G, Mahagne MH, et al: Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric
