- Email: [email protected]
Endovascular Mechanical Thrombectomy with the Solitaire Device for the Treatment of Acute Basilar Artery Occlusion
Accepted Manuscript Endovascular mechanical thrombectomy with the Solitaire device for the treatment of acute basilar artery occlusion Xiaochuan Huo, Ph.D, Feng Gao, Ph.D, Xuan Sun, Ph.D, Ning Ma, Ph.D, Ligang Song, Ph.D, Dapeng Mo, Ph.D, Lian Liu, Ph.D, Bo Wang, Ph.D, Xuelei Zhang, MD, Zhongrong Miao, Ph.D PII:
S1878-8750(16)00229-1
DOI:
10.1016/j.wneu.2016.02.017
Reference:
WNEU 3711
To appear in:
World Neurosurgery
Received Date: 3 January 2016 Revised Date:
3 February 2016
Accepted Date: 4 February 2016
Please cite this article as: Huo X, Gao F, Sun X, Ma N, Song L, Mo D, Liu L, Wang B, Zhang X, Miao Z, Endovascular mechanical thrombectomy with the Solitaire device for the treatment of acute basilar artery occlusion, World Neurosurgery (2016), doi: 10.1016/j.wneu.2016.02.017. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title page
AC C
EP
TE D
M AN U
SC
RI PT
Dear editor, Here is our paper for consideration to be published on "World Neurosurgery". The further information about the paper is in the following: Title: Endovascular mechanical thrombectomy with the Solitaire device for the treatment of acute basilar artery occlusion The Authors: Xiaochuan Huo1, Ph.D; Feng Gao1, Ph.D; Xuan Sun1, Ph.D; Ning Ma1, Ph.D; Ligang Song1, Ph.D; Dapeng Mo1, Ph.D; Lian Liu1, Ph.D; Bo Wang1 Ph.D; Xuelei Zhang1, MD; Zhongrong Miao1, Ph.D. Author affiliations: 1. Department of interventional neurology, Beijing Tiantan Hospital, Capital Medical University. Address: No.6, Tiantan Xili, Chongwen district, Beijing Tiantan Hospital, Beijing 100050, P.R.China. Telephone and Fax: Tel: 86-010-67098851 Fax: 86-010-67098542 Email: Xiaochuan Huo ([email protected]) Corresponding author: Zhongrong Miao Affiliation: Department of interventional neurology, Beijing Tiantan Hospital, Capital Medical University. Address: No.6, Tiantan Xili, Chongwen district, Beijing Tiantan Hospital, Beijing, 100050, P.R.China. E-mail: [email protected] Tel: 86-010-67098851 Fax: 86-010-67098542 Key Words: Acute Basilar Artery Occlusion, Mechanical Thrombectomy, Solitaire Device Abbreviations: ABAO=Acute basilar artery occlusion; IRB=Institutional Review Board; CTA=computed tomography angiography; MRA=magnetic resonance angiography; BAO=basilar artery occlusion; DWI=; GFR=Glomerular Filtration Rate; NIHSS= National Institutes of Health Stroke Scale; PTA=percutaneous transluminal angioplasty; DSA= Digital subtraction angiography; IQR= Inter Quartile Range; TICI= Thrombolysis in Cerebral Ischemia Scale; mRS= modified Rankin Scale; GCS= Glasgow coma scale; sICH= symptomatic intracranial hemorrhage;
Word count: 3,975 words
1
ACCEPTED MANUSCRIPT Endovascular mechanical thrombectomy with the Solitaire device for the treatment of acute basilar artery occlusion
RI PT
ABSTRACT Objective: To determine the safety and efficacy of endovascular treatment with the Solitaire device for acute basilar artery occlusion (ABAO) and identify factors affecting
SC
clinical outcomes.
Methods: We enrolled 36 consecutive ABAO patients (aged 58.6 ± 8.10 years) who
M AN U
underwent mechanical thrombectomy with the Solitaire device. We analyzed baseline characteristics, mechanical thrombectomy results, and factors predicting clinical outcomes, which were assessed at 90 days.
Results: The median pre-thrombectomy National Institutes of Health Stroke Scale score
was
25.50
(interquartile
range:
21.00–29.00);
the
median
TE D
(NIHSS)
pre-thrombectomy Glasgow coma scale (GCS) score was 8.00 (5.00–9.75). Thirty patients (83.3%) had atherosclerotic stenosis of the occluded artery, and 25 underwent
EP
angioplasty (69.4%). Recanalization was successful (Thrombolysis in Cerebral Infarction grade: 2b–3) in 34 patients (94.4%). Six symptomatic intracranial
AC C
hemorrhages (16.67%) occurred. Favorable outcomes (modified Rankin scale [mRS] score: 0–2) were achieved in 27.8% patients (10/36). The overall mortality rate was 30.6% (11/36) at 90 days. On univariate analysis, low pre-thrombectomy GCS and high post-thrombectomy NIHSS scores were associated with poor outcomes (mRS score >2) and mortality. Pre-thrombectomy unconsciousness, onset-to-recanalization time > 10.5 h, and severe stenosis were associated with poor outcomes. Age ≥ 60 years was associated with mortality.
2
ACCEPTED MANUSCRIPT Conclusions: Endovascular treatment with the Solitaire device yielded high recanalization rates in ABAO patients and favorable clinical outcomes in approximately one-third of patients. Intracranial stenosis was the main cause of occlusion. Angioplasty
RI PT
was commonly performed during mechanical thrombectomy to improve recanalization and prognosis. Early recanalization and better pre-thrombectomy status predicted better
SC
outcomes.
ABBREVIATIONS
M AN U
ABAO, acute basilar artery occlusion; NIHSS, National Institutes of Health Stroke Scale; GCS, Glasgow coma scale; mRS, modified Rankin scale; TICI, Thrombolysis in
AC C
EP
TE D
Cerebral Infarction.
3
ACCEPTED MANUSCRIPT INTRODUCTION Acute basilar artery occlusion (ABAO) carries a poor prognosis; it is associated with a mortality rate of approximately 90% and leads to severe neurological dysfunction
RI PT
in more than 65% of survivors1. Early recanalization is the main factor contributing to a relatively good prognosis in ABAO patients2-4. Endovascular mechanical thrombectomy increases recanalization rates and may thus improve patient outcomes4-6. Since
SC
September 2014, a series of randomized controlled trials have consistently reported that endovascular mechanical thrombectomy is clearly beneficial in selected cases of acute
M AN U
ischemic stroke (AIS)6-10. The SolitaireTM stent (ev3, Irvine, California) is one of the most promising devices for recanalization. This self-expanding and fully retrievable nitinol stent yields recanalization rates of up to 90% in patients with acute cerebral artery occlusion5-7. Recent studies8-12 have confirmed the effectiveness of the Solitaire
TE D
stent for mechanical thrombectomy in patients with AIS involving the anterior cerebral circulation. However, studies focusing on the safety and effectiveness of mechanical thrombectomy for AIS involving the posterior circulation are limited. In addition, the
EP
pathogenetic basis of AIS in the Asian population is mainly atherosclerotic stenosis, and studies on the safety and efficacy of the Solitaire device for treating ABAO in the
AC C
Chinese population are rare. The objective of this study is to determine the safety and efficacy of the Solitaire device for the endovascular treatment of ABAO in Chinese patients and to identify the factors related to the clinical outcome.
MATERIALS AND METHODS Patients This study involved 36 ABAO patients who had undergone endovascular treatment
4
ACCEPTED MANUSCRIPT with stent retrievers in Beijing Tiantan Hospital between March 2012 and March 2015. Patients fulfilling the following criteria were enrolled for endovascular treatment in this prospective study: (1) ABAO confirmed using computed tomography angiography
RI PT
(CTA) or magnetic resonance angiography (MRA); (2) mechanical thrombectomy with the Solitaire device; (3) AIS caused by atherosclerosis of a large artery, cardiac embolism, or thrombogenesis; (4) age ≥ 18 years; and (5) at least one indication for
SC
mechanical thrombectomy as judged by the Interventional Neurology Department of Beijing Tiantan Hospital.
M AN U
The indications for mechanical thrombectomy were as follows: (1) clinically diagnosed AIS causing evaluable neurological dysfunction (language, motor, and/or cognitive dysfunction; gaze palsy; defect in the field of vision; and/or visual neglect); (2) basilar artery occlusion or severe stenosis on cerebral vascular evaluation; (3) potential
TE D
benefit of endovascular treatment as determined using radiological imaging and clinical examination; and (4) provision of informed consent by the patient or the patient’s legally authorized representative after receiving information about data collection.
EP
The exclusion criteria for this study were as follows: (1) intracranial hemorrhage (ICH) on imaging examination; (2) large ischemic core (early ischemic changes
AC C
in >2/3rds of the area of the pons or midbrain) on baseline non-contrast computed tomography (CT) or diffusion-weighted imaging; (3) contrast allergy; (4) history of ICH, subarachnoid hemorrhage, arteriovenous malformation, or tumor; (5) severe disability (modified Rankin score [mRS] > 3); and (6) renal failure as indicated by serum creatinine > 2.0 mg/dl (177 µmol/l) or glomerular filtration rate < 30 ml/(min*1.73 m2).
Baseline data collection
5
ACCEPTED MANUSCRIPT Stroke neurologists assessed all the patients on admission, and recorded the National Institutes of Health Stroke Scale (NIHSS) scores. Multimodal magnetic resonance (MR) imaging (including diffusion-weighted imaging and MRA) was
RI PT
performed on admission unless contraindicated, in which case cerebral CT and CTA studies were performed. The baseline demographics, NIHSS and mRS scores on admission,
symptom-to-door
time,
door-to-puncture
time,
and
SC
puncture-to-recanalization time were documented. For patients with unknown symptom onset time, the last known time of normal health was taken as the symptom onset time.
Revascularization therapy
M AN U
The mRS score on day 90 of follow-up was also recorded.
All patients underwent revascularization therapy under general anesthesia. A 6F
TE D
guiding catheter was advanced into the V2 segment of the vertebral artery via transfemoral access. Intravenous heparin was administered to achieve an activated clotting time of 250–300 s. A microcatheter (Rebar microcatheter; Covidien, California,
EP
USA) was carefully navigated through the basilar occlusion over a 0.014-inch microwire (Transend; Stryker, Kalamazoo, Michigan) under fluoroscopic guidance.
AC C
Angiographic runs via the microcatheter were performed to confirm its location in the target artery with the catheter tip distal to the thrombus. The Solitaire AB device (ev3, Irvine, California) was used for mechanical thrombectomy. After advancement of the Solitaire device via the microcatheter to the occluded segment, the stent retriever was unsheathed and allowed to fully expand through the thrombus. The device thus served as a transient endovascular bypass to restore flow across the occluded segment. Then, angiography was performed to assess the distal vessel flow. Subsequently, the fully
6
ACCEPTED MANUSCRIPT deployed Solitaire device was partially resheathed. The device was gently pulled back as a single unit together with the delivery microcatheter for thrombectomy. If the procedure failed or if recanalization was insufficient the first time, further retrievals
Natick,
Scientific
Place,
RI PT
would be attempted. Balloon angioplasty (GatewayTM, Boston
MA) and stent placement would be considered if there was underlying severe
vertebrobasilar stenosis (more than 70%) causing inadequate distal perfusion, or if new
SC
thrombus formation or reocclusion was noted at the site of residual stenosis on repeat angiography up to 30 min after the thrombectomy. Once the decision to proceed to stent
M AN U
placement was made, loading doses of aspirin (300 mg) and clopidogrel (300 mg) were administered via a nasogastric tube in patients who had not previously taken antiplatelets. Pantoprazole was given for gastric protection. Stent placement was done with either the balloon-mounted Apollo stent (MicroPort Medical [Shanghai], Shanghai,
TE D
China) or the self-expanding Wingspan stent (manufactured by Stryker for Boston Scientific, Natick, Massachusetts).
These stents have an advantage over the Solitaire AB device because they provide a
EP
stronger radial force to overcome the underlying stenosis. Device selection depends on the vessel characteristics and lesion morphology, as previously described13,
14
. For
AC C
patients with tortuous arterial access and anticipated difficulty in stent passage, only percutaneous transluminal angioplasty (PTA) was performed. If patients were noted to have acute thrombosis over the stent or significant residual thrombosis impeding forward blood flow, glycoprotein IIb/IIIa inhibitor infusion (tirofiban) would be given. Follow-up CT was performed immediately postoperatively to exclude intracerebral hemorrhage. Transcranial Doppler, CTA, MRA, or digital subtraction angiography was performed within 24 h after the intervention to assess the patency of the basilar artery.
7
ACCEPTED MANUSCRIPT Patients were maintained on dual antiplatelet therapy with aspirin (100 mg) and clopidogrel (75 mg) for 3 months, followed by single antiplatelet therapy life-long for atherosclerotic stenosis. Patients were followed up at 90 days via clinic visits or via
RI PT
phone calls, if they could not attend follow-up. Follow-up CTA was arranged.
Outcome measures
SC
The primary outcome measure was the successful reperfusion rate, which was defined as a TICI grade of 2b or 3 after endovascular treatment. The other outcome
M AN U
measures recorded were intraoperative complications, including vessel perforation, arterial dissection, and symptomatic intracerebral hemorrhage (SICH), and other in-hospital neurologic complications. SICH was defined as a CT-documented hemorrhage that was temporally related to deterioration in the patient’s clinical
TE D
condition as judged by the clinical investigator. SICH attributable to the study medications was defined as a symptomatic hemorrhage that occurred within 36 h of treatment onset. The clinical outcomes evaluated were the functional outcome and
EP
vascular-related mortality at 90 days. A good functional outcome was defined as an
AC C
mRS score of 0–2.
Statistical analysis
Descriptive analysis included frequencies and percentages for categorical variables
and mean and SD or median (interquartile range [IQR]; 25%–75%) for continuous variables. Patients with favorable outcomes were compared with those with poor outcomes. The Student t-test or Wilcoxon rank test was used for continuous variables, and the χ2 test or Fisher exact test was used for categorical variables. Predictors of
8
ACCEPTED MANUSCRIPT prognosis were identified by univariate logistic regression. SPSS 17.0 (SPSS Inc.,
Chicago, Illinois) was used for statistical analyses.
RI PT
RESULTS Population data
Thirty-six consecutive patients with ABAO were treated with stent-assisted
SC
mechanical recanalization in our center. There were 15 male patients and 21 female patients. The mean age of the patients was 61 ± 17 years. The pre-thrombectomy
M AN U
clinical status was poor, with median NIHSS scores of 25.50 (IQR: 21.00–29.00) and median GCS scores of 8.00 (IQR: 5.00–9.75). The median time between symptom onset and admission to our emergency room was 274.50 min (IQR: 112.25–605.00 min). All patients were reported to have been symptom-free within the previous 24 h by their
TE D
family. The infarct etiology was atherothrombotic in 33 patients (91.67%), cardioembolic in 2 patients (5.56%), thrombogenesis in 1 patients (6%). A summary of
EP
the patients’ clinical and radiological characteristics has been presented in Table 1.
Treatment results
AC C
Of the 36 patients, 2 (5.56%) underwent intravenous recombinant tissue plasminogen activator thrombolysis before mechanical thrombectomy, and another 2 patients underwent intra-arterial thrombolysis during thrombectomy. The median number of thrombectomy device passes was 2 (IQR: 1–2). The median NIHSS score after thrombectomy was 23.50 (IQR: 12.25–27.00). In 2 patients, because of severe arterial stenosis, the Solitaire stent was released after balloon PTA without retrieval. The recanalization failed in 2 patients because of severe stenosis of the basilar artery and
9
ACCEPTED MANUSCRIPT repeated occlusion after balloon and stent angioplasty. Atherosclerotic stenosis of the basilar artery was found during thrombectomy in 30 patients (83.33%), and angioplasty was performed in 25 of these patients: balloon PTA
RI PT
alone, 8 patients; permanent intracranial stent placement alone, 5 patients; and balloon PTA combined with permanent stenting, 12 patients. Recanalization was successful in 34 patients (94.4%) with TICI grades ≥ 2b; furthermore, 88.9% of these patients
SC
achieved TICI grade 3. The median time between symptom onset and recanalization was 572.50 min (IQR: 473.00–787.50 min). The median door-to-puncture time was 175
Procedure-related complications
M AN U
min (IQR: 113.25–426.75 min; Table 2).
Six cases of SICH (16.67%) related to the acute therapy occurred in the
TE D
perioperative period. During thrombectomy, difficulty in retrieving the Solitaire stent was encountered in 1 patient, and the stent was released.
EP
Clinical outcomes
All the patients were followed up. The mortality rate was 30.56% (11/36) on day 90
AC C
of follow-up. Favorable outcomes (mRS scores: 0–2) were achieved in 10 patients, which represented 27.8% of all patients and 40.0% of the survivors (recanalization was successful in all 10 of these patients).
Predictive factors for clinical outcomes On univariate analysis, poor outcomes (mRS score > 2) were associated with pre-thrombectomy unconsciousness (P = 0.017, 95% confidence interval [CI]:
10
ACCEPTED MANUSCRIPT 2.44–9.10), pre-thrombectomy GCS score (P = 0.006, odds ratio [OR]: 0.68, 95% CI: 0.50–0.930), onset-to-recanalization time > 10.5 h (P = 0.022, OR: 12.27, 95% CI: 1.35–111.61), residual stenosis (P = 0.021, OR: 1.04, 95% CI: 1.00–1.08), and
RI PT
post-thrombectomy NIHSS score (P < 0.001, OR: 1.51, 95% CI: 1.12–2.03). Hyperglycemica (P = 0.070) and diabetes mellitus (P = 0.069) tended to be associated with poor clinical outcome, but the association did not reach statistical significance.
SC
Further analysis showed that pre-thrombectomy unconsciousness was associated with pre-thrombectomy GCS score (P < 0.001) and post-thrombectomy NIHSS score (P <
M AN U
0.001). Residual stenosis was associated with angioplasty (P = 0.015) and puncture-to-recanalization time (P = 0.017; Table 3).
We further calculated the cutoff value of the pre-thrombectomy GCS score and post-thrombectomy NIHSS score for predicting a poor outcome, by using the χ2 test or
TE D
Fisher exact test. A pre-thrombectomy GCS score of less than 8 and post-thrombectomy NIHSS score of greater than 28 predicted a poor clinical outcome.
EP
Predictive factors for mortality
On univariate analysis, mortality (death) was associated with age ≥ 60 years (P =
AC C
0.028, OR: 5.67, 95% CI: 1.18–27.25), pre-thrombectomy GCS score (P = 0.007, OR: 0.65, 95% CI: 0.46–0.92), post-thrombectomy NIHSS score (P < 0.001, OR: 1.71, 95% CI: 1.08–2.71), and recanalization without SICH (P = 0.018, OR: 0.10, 95% CI: 0.02–0.68). Baseline glycemia (P = 0.074), door-to-puncture time (P = 0.068), pre-thrombectomy mRS score (P = 0.059), and post-thrombectomy SICH (P = 0.057) tended to be associated with mortality, but did not reach statistical significance (Table 4).
11
ACCEPTED MANUSCRIPT We further calculated the cutoff value of pre-thrombectomy GCS scores and post-thrombectomy NIHSS scores for predicting mortality, by using the χ2 test or Fisher exact test. A pre-thrombectomy GCS score of less than 6 and post-thrombectomy
RI PT
NIHSS score of greater than 12 predicted high mortality.
DISCUSSION
SC
Endovascular therapy with a stent retriever is now recommended as the first choice of treatment in selected patients with large-artery occlusion involving the anterior
M AN U
cerebral circulation15-20. However, few randomized controlled trials have focused on the safety and effectiveness of mechanical thrombectomy for the posterior circulation, and only a few small-sample studies on mechanical thrombectomy have focused on ABAO 8-12, 21-23
. Roth et al.9 analyzed 12 patients with ABAO treated using Penumbra (a device
TE D
for aspiration thrombectomy) and intravenous thrombolysis. Andersson et al.8 examined 28 cases of ABAO treated using different clot retrievers and supplemental therapies such as intra-arterial thrombolysis and balloon angioplasty. Mordasini et al.10 treated 14
EP
ABAO patients with the Solitaire FR device. All 14 of these patients successfully underwent recanalization (TICI grades: 2b–3), and the mean number of passes was 1.3.
AC C
There was no symptomatic intracranial hemorrhage. At the 3-month follow-up, 28.6% patients (4/14) had achieved good functional outcomes (mRS scores: 0–2), and the total mortality was 35.7% (5/14). Espinosa et al.11 evaluated 18 patients with vertebrobasilar occlusion treated with a stent retriever, and reported that recanalization was successful in 94.4% patients (17/18; TICI grades: 2b–3). In addition, 50% of these patients (9/17) had good functional outcomes (mRS scores: 0–2). No symptomatic intracranial hemorrhage occurred, and the mortality rate was 22.2% (5/17). In a recent study,
12
ACCEPTED MANUSCRIPT Mourand et al.12 evaluated 31 ABAO patients treated with the Solitaire device within 24 h after symptom onset. Recanalization was successful in 23 of these patients (74%; TICI grades, 2b–3), and favorable outcomes (mRS scores: 0–2) were achieved in 35% of the
RI PT
patients (11/31). The total mortality rate was 32% (10/31). Mohlenbruch et al.21 evaluated 24 ABAO patients treated with the Solitaire FR or Revive SE device (Codman, US). Recanalization was successful in 18 of these patients (75%; TICI grades:
SC
2b–3), with a mortality of 29% (7/24) during the first 3 months. Favorable clinical outcomes (mRS scores: 0–2) were obtained in 8 patients (33%) after 3 months. Wang et
M AN U
al.22 studied 18 ABAO patients who underwent arterial interventional treatment with a recanalization rate of 94.4%. The average number of passes was 1.5, and the total mortality rate was 27.8% (5/18). Good prognoses were achieved in 38.9% patients. A recent study has also reported successful stent retrieval in children with ABAO23.
TE D
Recently a systematic review and meta-analysis found that Stent retriever thrombectomy achieves a high rate of recanalization and functional independence while being relatively safe for patients with BAO24.
EP
Approximately 26%–36% of ABAO patients have associated atherosclerotic lesions10. However, the main cause of ABAO in our population was atherothrombotic
AC C
occlusion, which was present in 91.67% patients (33/36), and this percentage was significantly higher than those reported in other studies (16%–29.2%)12, 21. Thrombi originating from ulcerated atherosclerotic plaques are usually stickier than embolic thrombi, which make the former more difficult to retrieve10. When compared with complete recanalization, partial recanalization of vessels with atherothrombotic lesions is more likely to be associated with reocclusion after stent retrieval, with reported reocclusion rates of 10%–30% after intra-arterial thrombolysis25, 26.
13
ACCEPTED MANUSCRIPT The rate of stenosis of the occluded artery was 83.33% (30/36) among the ABAO patients in our series, and 25 (69.4%) of these patients underwent angioplasty. The stenosis rate in our study is higher than the rates reported in previous studies. Many
RI PT
studies27-30 have reported the use of balloon PTA and intracranial stenting during the process of thrombolysis or thrombectomy in patients with vascular stenosis. These measures yielded recanalization rates of 70%–94%, which are higher than the rates
SC
achieved with intravenous or intra-arterial thrombolysis alone27-30. In our study, the rate of successful recanalization was 94.44% (34/36), which is comparable to that obtained
M AN U
in other series8-12, 21. In our study, when stenosis led to partial recanalization, balloon PTA and/or permanent intracranial stent implantation was performed an additional measure if there was inadequate distal perfusion, or if new thrombus formation or reocclusion was noted at the site of residual stenosis. Our previous experience has
TE D
shown that the combined use of mechanical thrombectomy with angioplasty and stent placement for ABAO with severe underlying intracranial atherosclerotic stenosis is technically feasible and safe14.
EP
The mean thrombectomy time with the SolitaireTM device in our series was lower (no statistically significant) than that obtained with the MERCITM device (105 min vs.
AC C
139 min); in addition, the mean retrieval times were lower with former than with the latter (1.7 times vs. 3 times)12. The high angioplasty rate made our thrombectomy procedure more time consuming. Therefore, the procedure time in our series involving the Solitaire device was greater than that reported in a recent study of thrombectomy in the posterior circulation (105 min vs. 61 min)12. Our results showed that SolitaireTM thrombectomy could effectively restore blood flow after ABAO and improve clinical outcomes. The rates of favorable outcomes (30%
14
ACCEPTED MANUSCRIPT vs. 20%–24%) and mortality (30% vs. 50%–56%) were better (no statistically significant) in our study than in previously reported studies of intravenous or intra-arterial thrombolysis2, 31. All these results indicated the technical feasibility and
RI PT
applicability of mechanical thrombectomy using stent retrieval to treat ABAO. However, despite the high rate of successful recanalization, the rate of favorable clinical outcomes was limited.
SC
In addition to successful recanalization, certain factors have been reported to predict clinical outcomes. In our study, we evaluated other predictors of clinical
M AN U
outcomes. Considering the high stenosis rate in our series, we recorded the rate of residual stenosis of the responsible artery after thrombectomy. Inconsistent with previous studies, we found that a higher residual stenosis rate was associated with poor clinical outcomes at 90 days (P = 0.021). It was more difficult to perform stent
TE D
thrombectomy in ABAO patients with severe arterial stenosis. Sometimes, the stent could not be passed through the stenosed artery without using balloon PTA. We also found that a higher residual stenosis rate was associated with angioplasty (P = 0.015).
residual
EP
This is because angioplasty was performed for ABAO patients with severe stenosis, and stenosis
was
common
even
after
angioplasty.
The
mean
AC C
puncture-to-recanalization time was longer (no statistically significant) in patients who underwent angioplasty than in those who did not undergo angioplasty (111 min vs. 91 min). We found that the residual stenosis rate was also associated with the puncture-to-recanalization time (P = 0.017). Taken together, our study included more atherosclerotic ABAO patients, and most of them required balloon PTA and/or stent placement for angioplasty, which might have caused additional complications, increased the operation time, and affected the clinical outcomes. Moreover, the degree of residual
15
ACCEPTED MANUSCRIPT stenosis might be related to the perfusion of the ischemic territory, and milder stenosis might be associated with better distal perfusion and better outcomes25,
26
. Thus, a
decrease in residual stenosis and in thrombectomy time was beneficial in ABAO
RI PT
patients. Besides the residual stenosis rate, pre-thrombectomy unconsciousness (P = 0.017), low pre-thrombectomy GCS score (P = 0.006), and high post-thrombectomy NIHSS
SC
score (P < 0.001) were associated with poor clinical outcomes. These three parameters were key factors reflecting the clinical status of the patients. Further analysis showed
M AN U
that pre-thrombectomy unconsciousness was associated with low pre-thrombectomy GCS scores (P < 0.001) and high post-thrombectomy NIHSS score (P < 0.001). Thus, we concluded that it is reasonable to predict clinical outcomes on the basis of consciousness status and neurological scores.
TE D
Another important factor affecting clinical outcome was the onset-to-recanalization time. Early recanalization has been significantly associated with better clinical outcomes 15, 32. The positive effect of early recanalization in the MR CLEAN trial was
EP
time-dependent, with the adjusted common OR decreasing from 3.0 (95% CI: 1.6–5.6) at an onset-to-recanalization time of 3.5 h, to 1.5 (95% CI: 1.1–2.2) at 6 h15. The
AC C
treatment effect was not statistically significant anymore when reperfusion was achieved after 6 h and 19 m. The benefit of thrombectomy was also shown to be time-dependent in the IMS III trial, where an increased time to reperfusion was associated with a decreased probability of a good functional outcome (adjusted relative risk for every 30-min delay: 0.88, 95% CI: 0.80–0.98)33. We found that a cutoff onset-to-recanalization time of 10.5 h was related with poor outcomes. Patients in whom the onset-to-recanalization time was more than 10.5 h had a higher rate of poor
16
ACCEPTED MANUSCRIPT outcomes (57.7%) than patients who underwent early recanalization (<10.5 h; 10%). Recently, Mourand et al.12 reported an association between elevated baseline glucose (P = 0.008) and poor outcomes (mRS score > 2). We found that patients with high baseline
RI PT
glucose (P = 0.070) and diabetes (P = 0.069) tended to have poor outcomes. This may be because patients with diabetes tended to have higher baseline glucose levels after ABAO (P = 0.064), and glucose control is important in AIS patients.
SC
The risk factors of mortality were also analyzed using our data. We found that age ≥ 60 years (P = 0.028), low pre-thrombectomy GCS score (P = 0.007), and high
M AN U
post-thrombectomy NIHSS score (P < 0.001) were associated with mortality. Baseline glycemia (P = 0.074), door-to-puncture time (P = 0.068), pre-thrombectomy mRS score (P = 0.059), and post-thrombectomy SICH (P = 0.057) tended to be associated with mortality. Thus, age and neurological scores could help predict mortality; however,
TE D
these factors are unmodifiable. The most important modifiable risk factors were those related to thrombectomy. We further found that successful recanalization without SICH was significantly associated with survival (P = 0.018). Thus, a high recanalization rate
EP
with low SICH was the objective of thrombectomy. With regard to hemorrhagic complications, the rate of SICH related to the
AC C
procedure was acceptable at 16.67% (6/36). However, this rate was higher than those reported with intravenous or intra-arterial thrombolysis alone2, 31, 34 but was comparable to those obtained with other interventions3, 35, 36. In our study, four of the patients with SICH died, and the other 2 had severe neurological dysfunction. One of these patients had been previously treated with intravenous thrombolysis, and in 2 patients, the hemorrhage was related to the manipulation during mechanical thrombectomy. Difficulty in retrieving the Solitaire stent was encountered in 1 patient, in whom the
17
ACCEPTED MANUSCRIPT stent was released in position. However, the stenosis was too severe for recanalization with the Solitaire stent, and a balloon expandable stent was deployed for angioplasty, which led to successful recanalization.
RI PT
In 2 patients, basilar artery reocclusion occurred after recanalization. In 1 patient, reocclusion occurred 4 days after the Solitaire thrombectomy and stent angioplasty because of incompliance with the dual antiplatelet therapy. Emergency angiography was
SC
performed in this patient, and the basilar artery was successfully recanalized again by using intra-arterial thrombolysis combined with balloon PTA. In the other patient,
M AN U
reocclusion occurred 2 months after SolitaireTM thrombectomy because of 50% residual stenosis; in this patient, repeat recanalization was performed using stent angioplasty. In our series, we found a high rate of recanalization and favorable outcomes in ABAO patients treated with Solitaire stent thrombectomy, even though there were
TE D
hemorrhagic and ischemic complications. There are certain limitations to our study, which focused on a very specific population. The number of patients in our study was relatively small, and the study had limited statistical power despite the fact that this is
EP
one of the largest stent retrieval series in Asian ABAO patients. In future, we intend to undertake a randomized controlled trial on this topic to better evaluate the effects of
AC C
endovascular thrombectomy in ABAO patients.
Conclusion
Solitaire thrombectomy resulted in a high recanalization rate in ABAO patients,
with favorable clinical outcomes in approximately one-third of patients. Intracranial stenosis was the main cause of ABAO, and angioplasty was commonly performed during mechanical thrombectomy for better recanalization and prognosis. The technical
18
ACCEPTED MANUSCRIPT outcomes of patients with ABAO can be improved by avoiding hemorrhagic complications and decreasing the residual stenosis rate. Early recanalization and relatively good pre-thrombectomy status predict favorable outcomes. More, large,
predictive factors for clinical outcomes. References
5.
6.
7.
8.
9. 10.
11.
12. 13.
14.
15. 16.
SC
M AN U
4.
TE D
3.
EP
2.
Schonewille WJ, Algra A, Serena J. Outcome in patients with basilar artery occlusion treated conventionally Journal of neurology, neurosurgery, and psychiatry. 2005; 76: 1238-1241. Lindsberg PJ, Mattle HP Therapy of basilar artery occlusion: a systematic analysis comparing intra-arterial and intravenous thrombolysis Stroke; a journal of cerebral circulation. 2006; 37: 922-928. Eckert B, Kucinski T, Pfeiffer G. Endovascular therapy of acute vertebrobasilar occlusion: early treatment onset as the most important factor Cerebrovascular diseases. 2002; 14: 42-50. Lutsep HL, Rymer MM, Nesbit GM Vertebrobasilar revascularization rates and outcomes in the MERCI and multi-MERCI trials Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 2008; 17: 55-57. Costalat V, Machi P, Lobotesis K. Rescue, combined, and stand-alone thrombectomy in the management of large vessel occlusion stroke using the solitaire device: a prospective 50-patient single-center study: timing, safety, and efficacy Stroke; a journal of cerebral circulation. 2011; 42: 1929-1935. Roth C, Papanagiotou P, Behnke S. Stent-assisted mechanical recanalization for treatment of acute intracerebral artery occlusions Stroke; a journal of cerebral circulation. 2010; 41: 2559-2567. Castano C, Dorado L, Guerrero C. Mechanical thrombectomy with the Solitaire AB device in large artery occlusions of the anterior circulation: a pilot study Stroke; a journal of cerebral circulation. 2010; 41: 1836-1840. Andersson T, Kuntze Soderqvist A, Soderman M. Mechanical thrombectomy as the primary treatment for acute basilar artery occlusion: experience from 5 years of practice Journal of neurointerventional surgery. 2013; 5: 221-225. Roth C, Mielke A, Siekmann R. First experiences with a new device for mechanical thrombectomy in acute basilar artery occlusion Cerebrovascular diseases. 2011; 32: 28-34. Mordasini P, Brekenfeld C, Byrne JV. Technical feasibility and application of mechanical thrombectomy with the Solitaire FR Revascularization Device in acute basilar artery occlusion AJNR. American journal of neuroradiology. 2013; 34: 159-163. Espinosa de Rueda M, Parrilla G, Zamarro J. Treatment of acute vertebrobasilar occlusion using thrombectomy with stent retrievers: initial experience with 18 patients AJNR. American journal of neuroradiology. 2013; 34: 1044-1048. Mourand I, Machi P, Milhaud D. Mechanical thrombectomy with the Solitaire device in acute basilar artery occlusion Journal of neurointerventional surgery. 2014; 6: 200-204. Miao Z, Song L, Liebeskind DS. Outcomes of tailored angioplasty and/or stenting for symptomatic intracranial atherosclerosis: a prospective cohort study after SAMMPRIS Journal of neurointerventional surgery. 2015; 7: 331-335. Gao F, Lo WT, Sun X. Combined Use of Mechanical Thrombectomy with Angioplasty and Stenting for Acute Basilar Occlusions with Underlying Severe Intracranial Vertebrobasilar Stenosis: Preliminary Experience from a Single Chinese Center AJNR. American journal of neuroradiology. 2015 Berkhemer OA, Fransen PS, Beumer D. A randomized trial of intraarterial treatment for acute ischemic stroke The New England journal of medicine. 2015; 372: 11-20. Goyal M, Demchuk AM, Menon BK. Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke The New England journal of medicine. 2015
AC C
1.
RI PT
prospective, multicenter studies with the Solitaire device are needed to identify
19
ACCEPTED MANUSCRIPT
23. 24.
25. 26.
27.
28.
29.
30. 31. 32.
33.
34.
35.
36.
RI PT
22.
SC
21.
M AN U
20.
TE D
19.
EP
18.
Saver JL, Goyal M, Bonafe A. Stent-Retriever Thrombectomy after Intravenous t-PA vs. t-PA Alone in Stroke The New England journal of medicine. 2015 Campbell BC, Mitchell PJ, Kleinig TJ. Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection The New England journal of medicine. 2015 Jovin TG, Chamorro A, Cobo E. Thrombectomy within 8 Hours after Symptom Onset in Ischemic Stroke The New England journal of medicine. 2015 Powers WJ, Derdeyn CP, Biller J. 2015 AHA/ASA Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association Stroke; a journal of cerebral circulation. 2015 Mohlenbruch M, Stampfl S, Behrens L. Mechanical thrombectomy with stent retrievers in acute basilar artery occlusion AJNR. American journal of neuroradiology. 2014; 35: 959-964. Wang L, Shi W, Su Z. Endovascular treatment of severe acute basilar artery occlusion Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2015; 22: 195-198. Savastano L, Gemmete JJ, Pandey AS. Acute ischemic stroke in a child due to basilar artery occlusion treated successfully with a stent retriever Journal of neurointerventional surgery. 2015 Phan K, Phan S, Huo YR. Outcomes of endovascular treatment of basilar artery occlusion in the stent retriever era: a systematic review and meta-analysis Journal of neurointerventional surgery. 2015 Becker KJ, Monsein LH, Ulatowski J. Intraarterial thrombolysis in vertebrobasilar occlusion AJNR. American journal of neuroradiology. 1996; 17: 255-262. Zeumer H, Freitag HJ, Zanella F. Local intra-arterial fibrinolytic therapy in patients with stroke: urokinase versus recombinant tissue plasminogen activator (r-TPA) Neuroradiology. 1993; 35: 159-162. Jung S, Mono ML, Fischer U. Three-month and long-term outcomes and their predictors in acute basilar artery occlusion treated with intra-arterial thrombolysis Stroke; a journal of cerebral circulation. 2011; 42: 1946-1951. Kashiwagi J, Kiyosue H, Hori Y. Endovascular recanalization of acute intracranial vertebrobasilar artery occlusion using local fibrinolysis and additional balloon angioplasty Neuroradiology. 2010; 52: 361-370. Chandra RV, Law CP, Yan B. Glasgow coma scale does not predict outcome post-intra-arterial treatment for basilar artery thrombosis AJNR. American journal of neuroradiology. 2011; 32: 576-580. Yu YY, Niu L, Gao L. Intraarterial thrombolysis and stent placement for acute basilar artery occlusion Journal of vascular and interventional radiology : JVIR. 2010; 21: 1359-1363. Smith WS Intra-arterial thrombolytic therapy for acute basilar occlusion: pro Stroke; a journal of cerebral circulation. 2007; 38: 701-703. Qureshi AI, Abd-Allah F, Aleu A. Endovascular treatment for acute ischemic stroke patients: implications and interpretation of IMS III, MR RESCUE, and SYNTHESIS EXPANSION trials: A report from the Working Group of International Congress of Interventional Neurology Journal of vascular and interventional neurology. 2014; 7: 56-75. Khatri P, Yeatts SD, Mazighi M. Time to angiographic reperfusion and clinical outcome after acute ischaemic stroke: an analysis of data from the Interventional Management of Stroke (IMS III) phase 3 trial Lancet neurology. 2014; 13: 567-574. Lindsberg PJ, Soinne L, Tatlisumak T. Long-term outcome after intravenous thrombolysis of basilar artery occlusion JAMA : the journal of the American Medical Association. 2004; 292: 1862-1866. Nagel S, Schellinger PD, Hartmann M. Therapy of acute basilar artery occlusion: intraarterial thrombolysis alone vs bridging therapy Stroke; a journal of cerebral circulation. 2009; 40: 140-146. Raphaeli G, Eichel R, Ben-Hur T. Multimodal reperfusion therapy in patients with acute basilar artery occlusion Neurosurgery. 2009; 65: 548-552; discussion 552-543.
AC C
17.
20
ACCEPTED MANUSCRIPT
Table 1. Summary of Patient Characteristics Value 36 30(83.3) 58.6(8.10)
SC
RI PT
28(77.7) 23(63.9) 25(69.4) 12(33.3) 2(5.6) 4(11.1) 33(91.7) 9.80 (4.87) 149.00(135.25-173.75) 5(5-5) 25.50 (21.00-29.00) 8.00(5.00-9.75)
AC C
EP
TE D
M AN U
Characteristics Number of patients Male sex (%) Age (yr) , mean (SD) Past history, n (%) Smoke Drink Hypertension Diabetes Atrial fibrillation TIA Pre-thrombectomy unconsciousness, n (%) Baseline glycemia (mmol/l), mean (SD) Admission SBP (mmHg), median (IQR) Pretreatment mRS score, median (IQR) Pretreatment NIHSS score, median (IQR) Pretreatment GCS score, median (IQR) Stroke type, n (%) Atherosclerosis Cardioembolism Thrombogenesis Stenosis of occlusion artery, n (%)
1
33 (91.7) 2(5.6) 1(2.8) 30(83.3)
ACCEPTED MANUSCRIPT
Table 2. Summary of Treatment, and Outcome Value 274.50(112.25-605.00) 175.00(113.25-426.75) 90.00(60.00-125.00) 572.50(473.00-787.50)
GP IIb/IIIa inhibitor given, n (%)
13(36.1)
Angioplasty, n (%) Balloon PTA Stent PTA+Stent Retrieval times, median (IQR) TICI, n (%) 0 2b 3
25(69.4) 8(22.2) 5(13.9) 12(33.3) 2(1-2)
SC
2(5.6) 11(30.6)
RI PT
Characteristics Onset-to-door time, median (IQR) Door-to-puncture time, median (IQR) Puncture-to-recanalization time, median (IQR) Onset-to-recanalization, median (IQR) Combined tPA, n (%) IV tPA IA tPA
M AN U
2(5.6) 2(5.6) 32(88.9)
Stenosis rate post thrombectomy and angioplasty mean 26.0% median 20.0%
AC C
EP
TE D
Post-treatment NIHSS score, median (IQR) sICH, n (%) mRS at 90 days, n (%) 0 1 2 3 4 5 6 mRS 0-2 at 90 days, n (%) Mortality at 90 days, n (%)
2
23.50(12.25-27.00) 6(16.7) 5(13.9) 1 4 6 3 6 11 10(27.8) 11(30.6)
ACCEPTED MANUSCRIPT
Table 3. Risk factors for clinical outcome value 38.9%
n 12
Pre-thrombectomy Unconsciousness Baseline glycemia (mmol/l), mean (SD) Diabetes mellitus Pre-thrombectomy GCS score, median (IQR) Pre-thrombectomy mRS score, median (IQR) Angioplasty Residual stenosis (%), mean (SD) Puncture-to-recanalization time, median (IQR) Onset-to-recanalization time > 10.5 h Post-thrombectomy NIHSS score, median (IQR) sICH
33 36 12 36 36 25 36 34 16 36 6
91.7% 9.80 (4.87) 33.3% 8.00(5.00-9.75) 5.00(5.00-5.00) 69.4% 25.97(28.10) 90.00(60.00-125.00) 44.4% 23.50(12.25-27.00) 16.7%
26 26 11 26 26 19 26 26 15 26 6
100.0% 10.71(5.09) 42.3% 6.00(5.00-8.25) 5.00(5.00-5.00) 73.1% 31.35(29.91) 90.00(70.50-135.00) 57.7% 26.00(21.75-30.00) 23.1%
Favorable Outcome (mRS≤ ≤2) △ n value 4 40.0%
p Value*
Raw OR (95%CI)
0.519
1.29(0.29-5.66)
7 10 1 10 10 6 10 8 1 10 0
0.017* 0.070 0.069 0.006* 0.420 0.353 0.021* 0.358 0.022* <0.001* 0.118
M AN U
SC
RI PT
age≥60
n 16
Poor Outcome (mRS>2) △ value 46.2%
All patients
70.0% 7.43(3.43) 10.0% 9.50(7.25-12.50) 5.00(4.75-5.00) 60.0% 12(16.87) 87.00(53.50-127.50) 10.0% 8.50(5.25-12.5) 0.0%
#
/ (2.44-9.10) 1.29(0.96-1.73) 6.60(0.73-60.02) 0.68(0.50-0.93) 1.70(0.66-4.41) 1.81(0.39-8.39) 1.04(1.00-1.08) 1.00 12.27 (1.35-111.61) 1.51(1.12-2.03) 1.30(1.05-1.61)
AC C
EP
TE D
*p Values from Student t test or Wilcoxon rank sum test for continuous variables and the χ2 test or Fisher exact for categorical variables. # OR from logistic analysis. △ Percentage by group (poor and favorable outcome). GCS, Glasgow Coma Scale; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; sICH, symptomatic Intracranial Hemorrhage.
3
ACCEPTED MANUSCRIPT
Death △ Value 72.7% 100.0% 11.98(6.31) 45.5% 5.00(3.00-6.00) 5.00(5.00-5.00) 63.6% 28.64(33.02) 97.50(76.50-127.50) 30.00(26.00-35.00) 36.4% 90.9% 54.5%
SC
n 8 11 11 5 11 11 7 11 10 11 4 10 6
M AN U
age≥60 Pre-thrombectomy unconsciousness Baseline glycemia (mmol/l), mean (SD) Diabetes mellitus Pre-thrombectomy GCS score, median (IQR) Pre-thrombectomy mRS score, median (IQR) Angioplasty Residual stenosis (%), mean (SD) Puncture-to-Recanalization time, median (IQR) Post-thrombectomy NIHSS score, median (IQR) sICH Recanalization Recanalization without sICH
n 16 33 36 12 36 36 25 36 34 36 6 34 29
RI PT
Table 4. Risk factors for mortality All patients Value 38.9% 91.7% 9.80 (4.87) 33.3% 8.00(5.00-9.75) 5(5-5) 69.4% 25.97(28.10) 90.00(60.00-125.00) 23.50(12.25-27.00) 16.67% 94.4% 80.6%
n 8 22 25 7 25 25 18 25 24 25 2 24 23
Survival △ Value 32.0% 88.0% 8.84(5.95-11.12) 28.0% 8.00(6.00-10.50) 5.00(5.00-5.00) 72.0% 24.80(26.32) 90.00(60.00-135.00) 18.00(9.50-24.00) 8.0% 96.0% 92.0%
#
p Value*
Raw OR (95%CI)
0.028* 0.322 0.074 0.259 0.007* 0.059 0.449 0.712 0.857 <0.001* 0.057 0.524 0.018*
5.67(1.18-27.25) / (1.18-1.91) 1.14(0.98-1.33) 2.14(0.49-9.35) 0.65(0.46-0.92) / 0.68(0.15-3.07) 1.01(0.98-1.03) 1(0.99-1.01) 1.71(1.08-2.71) 6.57(0.99-43.78) 0.42(0.02-7.34) 0.10(0.02-0.68)
AC C
EP
TE D
*p Values from Student t test or Wilcoxon rank sum test for continuous variables and the χ2 test or Fisher exact for categorical variables. # OR from logistic analysis. △ Percentage by group (Death and survival). GCS, Glasgow Coma Scale; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; sICH, symptomatic Intracranial Hemorrhage.
4
AC C
EP
TE D
M AN U
SC
Abbreviations: ABAO=Acute basilar artery occlusion; BAO=basilar artery occlusion; CTA=Computed tomography angiography; DSA= Digital subtraction angiography; DWI=Diffusion Weighted Imaging; GCS= Glasgow coma scale; GFR=Glomerular Filtration Rate; IQR= Inter Quartile Range; IRB=Institutional Review Board; MRA=Magnetic resonance angiography; mRS= modified Rankin Scale; NIHSS=National Institutes of Health Stroke Scale; PTA=Percutaneous transluminal angioplasty; sICH= symptomatic intracranial hemorrhage; TICI= Thrombolysis in Cerebral Ischemia Scale;
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
Highlights: SolitaireTM thrombectomy resulted in a high recanalization rate for ABAO and the clinical outcome was favorable in about one-third of
RI PT
patients. Intracranial stenosis was main reason for ABAO and angioplasty was commonly performed during mechanical thrombectomy for a better recanalization and prognosis in China.
SC
The technical outcomes of patients with ABAO could be improved by avoiding hemorrhagic complications and decreasing residual stenosis
M AN U
rate.
Early recanalization and better pre-thrombectomy status predicts a
AC C
EP
TE D
better outcome.
S1878-8750(16)00229-1
DOI:
10.1016/j.wneu.2016.02.017
Reference:
WNEU 3711
To appear in:
World Neurosurgery
Received Date: 3 January 2016 Revised Date:
3 February 2016
Accepted Date: 4 February 2016
Please cite this article as: Huo X, Gao F, Sun X, Ma N, Song L, Mo D, Liu L, Wang B, Zhang X, Miao Z, Endovascular mechanical thrombectomy with the Solitaire device for the treatment of acute basilar artery occlusion, World Neurosurgery (2016), doi: 10.1016/j.wneu.2016.02.017. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title page
AC C
EP
TE D
M AN U
SC
RI PT
Dear editor, Here is our paper for consideration to be published on "World Neurosurgery". The further information about the paper is in the following: Title: Endovascular mechanical thrombectomy with the Solitaire device for the treatment of acute basilar artery occlusion The Authors: Xiaochuan Huo1, Ph.D; Feng Gao1, Ph.D; Xuan Sun1, Ph.D; Ning Ma1, Ph.D; Ligang Song1, Ph.D; Dapeng Mo1, Ph.D; Lian Liu1, Ph.D; Bo Wang1 Ph.D; Xuelei Zhang1, MD; Zhongrong Miao1, Ph.D. Author affiliations: 1. Department of interventional neurology, Beijing Tiantan Hospital, Capital Medical University. Address: No.6, Tiantan Xili, Chongwen district, Beijing Tiantan Hospital, Beijing 100050, P.R.China. Telephone and Fax: Tel: 86-010-67098851 Fax: 86-010-67098542 Email: Xiaochuan Huo ([email protected]) Corresponding author: Zhongrong Miao Affiliation: Department of interventional neurology, Beijing Tiantan Hospital, Capital Medical University. Address: No.6, Tiantan Xili, Chongwen district, Beijing Tiantan Hospital, Beijing, 100050, P.R.China. E-mail: [email protected] Tel: 86-010-67098851 Fax: 86-010-67098542 Key Words: Acute Basilar Artery Occlusion, Mechanical Thrombectomy, Solitaire Device Abbreviations: ABAO=Acute basilar artery occlusion; IRB=Institutional Review Board; CTA=computed tomography angiography; MRA=magnetic resonance angiography; BAO=basilar artery occlusion; DWI=; GFR=Glomerular Filtration Rate; NIHSS= National Institutes of Health Stroke Scale; PTA=percutaneous transluminal angioplasty; DSA= Digital subtraction angiography; IQR= Inter Quartile Range; TICI= Thrombolysis in Cerebral Ischemia Scale; mRS= modified Rankin Scale; GCS= Glasgow coma scale; sICH= symptomatic intracranial hemorrhage;
Word count: 3,975 words
1
ACCEPTED MANUSCRIPT Endovascular mechanical thrombectomy with the Solitaire device for the treatment of acute basilar artery occlusion
RI PT
ABSTRACT Objective: To determine the safety and efficacy of endovascular treatment with the Solitaire device for acute basilar artery occlusion (ABAO) and identify factors affecting
SC
clinical outcomes.
Methods: We enrolled 36 consecutive ABAO patients (aged 58.6 ± 8.10 years) who
M AN U
underwent mechanical thrombectomy with the Solitaire device. We analyzed baseline characteristics, mechanical thrombectomy results, and factors predicting clinical outcomes, which were assessed at 90 days.
Results: The median pre-thrombectomy National Institutes of Health Stroke Scale score
was
25.50
(interquartile
range:
21.00–29.00);
the
median
TE D
(NIHSS)
pre-thrombectomy Glasgow coma scale (GCS) score was 8.00 (5.00–9.75). Thirty patients (83.3%) had atherosclerotic stenosis of the occluded artery, and 25 underwent
EP
angioplasty (69.4%). Recanalization was successful (Thrombolysis in Cerebral Infarction grade: 2b–3) in 34 patients (94.4%). Six symptomatic intracranial
AC C
hemorrhages (16.67%) occurred. Favorable outcomes (modified Rankin scale [mRS] score: 0–2) were achieved in 27.8% patients (10/36). The overall mortality rate was 30.6% (11/36) at 90 days. On univariate analysis, low pre-thrombectomy GCS and high post-thrombectomy NIHSS scores were associated with poor outcomes (mRS score >2) and mortality. Pre-thrombectomy unconsciousness, onset-to-recanalization time > 10.5 h, and severe stenosis were associated with poor outcomes. Age ≥ 60 years was associated with mortality.
2
ACCEPTED MANUSCRIPT Conclusions: Endovascular treatment with the Solitaire device yielded high recanalization rates in ABAO patients and favorable clinical outcomes in approximately one-third of patients. Intracranial stenosis was the main cause of occlusion. Angioplasty
RI PT
was commonly performed during mechanical thrombectomy to improve recanalization and prognosis. Early recanalization and better pre-thrombectomy status predicted better
SC
outcomes.
ABBREVIATIONS
M AN U
ABAO, acute basilar artery occlusion; NIHSS, National Institutes of Health Stroke Scale; GCS, Glasgow coma scale; mRS, modified Rankin scale; TICI, Thrombolysis in
AC C
EP
TE D
Cerebral Infarction.
3
ACCEPTED MANUSCRIPT INTRODUCTION Acute basilar artery occlusion (ABAO) carries a poor prognosis; it is associated with a mortality rate of approximately 90% and leads to severe neurological dysfunction
RI PT
in more than 65% of survivors1. Early recanalization is the main factor contributing to a relatively good prognosis in ABAO patients2-4. Endovascular mechanical thrombectomy increases recanalization rates and may thus improve patient outcomes4-6. Since
SC
September 2014, a series of randomized controlled trials have consistently reported that endovascular mechanical thrombectomy is clearly beneficial in selected cases of acute
M AN U
ischemic stroke (AIS)6-10. The SolitaireTM stent (ev3, Irvine, California) is one of the most promising devices for recanalization. This self-expanding and fully retrievable nitinol stent yields recanalization rates of up to 90% in patients with acute cerebral artery occlusion5-7. Recent studies8-12 have confirmed the effectiveness of the Solitaire
TE D
stent for mechanical thrombectomy in patients with AIS involving the anterior cerebral circulation. However, studies focusing on the safety and effectiveness of mechanical thrombectomy for AIS involving the posterior circulation are limited. In addition, the
EP
pathogenetic basis of AIS in the Asian population is mainly atherosclerotic stenosis, and studies on the safety and efficacy of the Solitaire device for treating ABAO in the
AC C
Chinese population are rare. The objective of this study is to determine the safety and efficacy of the Solitaire device for the endovascular treatment of ABAO in Chinese patients and to identify the factors related to the clinical outcome.
MATERIALS AND METHODS Patients This study involved 36 ABAO patients who had undergone endovascular treatment
4
ACCEPTED MANUSCRIPT with stent retrievers in Beijing Tiantan Hospital between March 2012 and March 2015. Patients fulfilling the following criteria were enrolled for endovascular treatment in this prospective study: (1) ABAO confirmed using computed tomography angiography
RI PT
(CTA) or magnetic resonance angiography (MRA); (2) mechanical thrombectomy with the Solitaire device; (3) AIS caused by atherosclerosis of a large artery, cardiac embolism, or thrombogenesis; (4) age ≥ 18 years; and (5) at least one indication for
SC
mechanical thrombectomy as judged by the Interventional Neurology Department of Beijing Tiantan Hospital.
M AN U
The indications for mechanical thrombectomy were as follows: (1) clinically diagnosed AIS causing evaluable neurological dysfunction (language, motor, and/or cognitive dysfunction; gaze palsy; defect in the field of vision; and/or visual neglect); (2) basilar artery occlusion or severe stenosis on cerebral vascular evaluation; (3) potential
TE D
benefit of endovascular treatment as determined using radiological imaging and clinical examination; and (4) provision of informed consent by the patient or the patient’s legally authorized representative after receiving information about data collection.
EP
The exclusion criteria for this study were as follows: (1) intracranial hemorrhage (ICH) on imaging examination; (2) large ischemic core (early ischemic changes
AC C
in >2/3rds of the area of the pons or midbrain) on baseline non-contrast computed tomography (CT) or diffusion-weighted imaging; (3) contrast allergy; (4) history of ICH, subarachnoid hemorrhage, arteriovenous malformation, or tumor; (5) severe disability (modified Rankin score [mRS] > 3); and (6) renal failure as indicated by serum creatinine > 2.0 mg/dl (177 µmol/l) or glomerular filtration rate < 30 ml/(min*1.73 m2).
Baseline data collection
5
ACCEPTED MANUSCRIPT Stroke neurologists assessed all the patients on admission, and recorded the National Institutes of Health Stroke Scale (NIHSS) scores. Multimodal magnetic resonance (MR) imaging (including diffusion-weighted imaging and MRA) was
RI PT
performed on admission unless contraindicated, in which case cerebral CT and CTA studies were performed. The baseline demographics, NIHSS and mRS scores on admission,
symptom-to-door
time,
door-to-puncture
time,
and
SC
puncture-to-recanalization time were documented. For patients with unknown symptom onset time, the last known time of normal health was taken as the symptom onset time.
Revascularization therapy
M AN U
The mRS score on day 90 of follow-up was also recorded.
All patients underwent revascularization therapy under general anesthesia. A 6F
TE D
guiding catheter was advanced into the V2 segment of the vertebral artery via transfemoral access. Intravenous heparin was administered to achieve an activated clotting time of 250–300 s. A microcatheter (Rebar microcatheter; Covidien, California,
EP
USA) was carefully navigated through the basilar occlusion over a 0.014-inch microwire (Transend; Stryker, Kalamazoo, Michigan) under fluoroscopic guidance.
AC C
Angiographic runs via the microcatheter were performed to confirm its location in the target artery with the catheter tip distal to the thrombus. The Solitaire AB device (ev3, Irvine, California) was used for mechanical thrombectomy. After advancement of the Solitaire device via the microcatheter to the occluded segment, the stent retriever was unsheathed and allowed to fully expand through the thrombus. The device thus served as a transient endovascular bypass to restore flow across the occluded segment. Then, angiography was performed to assess the distal vessel flow. Subsequently, the fully
6
ACCEPTED MANUSCRIPT deployed Solitaire device was partially resheathed. The device was gently pulled back as a single unit together with the delivery microcatheter for thrombectomy. If the procedure failed or if recanalization was insufficient the first time, further retrievals
Natick,
Scientific
Place,
RI PT
would be attempted. Balloon angioplasty (GatewayTM, Boston
MA) and stent placement would be considered if there was underlying severe
vertebrobasilar stenosis (more than 70%) causing inadequate distal perfusion, or if new
SC
thrombus formation or reocclusion was noted at the site of residual stenosis on repeat angiography up to 30 min after the thrombectomy. Once the decision to proceed to stent
M AN U
placement was made, loading doses of aspirin (300 mg) and clopidogrel (300 mg) were administered via a nasogastric tube in patients who had not previously taken antiplatelets. Pantoprazole was given for gastric protection. Stent placement was done with either the balloon-mounted Apollo stent (MicroPort Medical [Shanghai], Shanghai,
TE D
China) or the self-expanding Wingspan stent (manufactured by Stryker for Boston Scientific, Natick, Massachusetts).
These stents have an advantage over the Solitaire AB device because they provide a
EP
stronger radial force to overcome the underlying stenosis. Device selection depends on the vessel characteristics and lesion morphology, as previously described13,
14
. For
AC C
patients with tortuous arterial access and anticipated difficulty in stent passage, only percutaneous transluminal angioplasty (PTA) was performed. If patients were noted to have acute thrombosis over the stent or significant residual thrombosis impeding forward blood flow, glycoprotein IIb/IIIa inhibitor infusion (tirofiban) would be given. Follow-up CT was performed immediately postoperatively to exclude intracerebral hemorrhage. Transcranial Doppler, CTA, MRA, or digital subtraction angiography was performed within 24 h after the intervention to assess the patency of the basilar artery.
7
ACCEPTED MANUSCRIPT Patients were maintained on dual antiplatelet therapy with aspirin (100 mg) and clopidogrel (75 mg) for 3 months, followed by single antiplatelet therapy life-long for atherosclerotic stenosis. Patients were followed up at 90 days via clinic visits or via
RI PT
phone calls, if they could not attend follow-up. Follow-up CTA was arranged.
Outcome measures
SC
The primary outcome measure was the successful reperfusion rate, which was defined as a TICI grade of 2b or 3 after endovascular treatment. The other outcome
M AN U
measures recorded were intraoperative complications, including vessel perforation, arterial dissection, and symptomatic intracerebral hemorrhage (SICH), and other in-hospital neurologic complications. SICH was defined as a CT-documented hemorrhage that was temporally related to deterioration in the patient’s clinical
TE D
condition as judged by the clinical investigator. SICH attributable to the study medications was defined as a symptomatic hemorrhage that occurred within 36 h of treatment onset. The clinical outcomes evaluated were the functional outcome and
EP
vascular-related mortality at 90 days. A good functional outcome was defined as an
AC C
mRS score of 0–2.
Statistical analysis
Descriptive analysis included frequencies and percentages for categorical variables
and mean and SD or median (interquartile range [IQR]; 25%–75%) for continuous variables. Patients with favorable outcomes were compared with those with poor outcomes. The Student t-test or Wilcoxon rank test was used for continuous variables, and the χ2 test or Fisher exact test was used for categorical variables. Predictors of
8
ACCEPTED MANUSCRIPT prognosis were identified by univariate logistic regression. SPSS 17.0 (SPSS Inc.,
Chicago, Illinois) was used for statistical analyses.
RI PT
RESULTS Population data
Thirty-six consecutive patients with ABAO were treated with stent-assisted
SC
mechanical recanalization in our center. There were 15 male patients and 21 female patients. The mean age of the patients was 61 ± 17 years. The pre-thrombectomy
M AN U
clinical status was poor, with median NIHSS scores of 25.50 (IQR: 21.00–29.00) and median GCS scores of 8.00 (IQR: 5.00–9.75). The median time between symptom onset and admission to our emergency room was 274.50 min (IQR: 112.25–605.00 min). All patients were reported to have been symptom-free within the previous 24 h by their
TE D
family. The infarct etiology was atherothrombotic in 33 patients (91.67%), cardioembolic in 2 patients (5.56%), thrombogenesis in 1 patients (6%). A summary of
EP
the patients’ clinical and radiological characteristics has been presented in Table 1.
Treatment results
AC C
Of the 36 patients, 2 (5.56%) underwent intravenous recombinant tissue plasminogen activator thrombolysis before mechanical thrombectomy, and another 2 patients underwent intra-arterial thrombolysis during thrombectomy. The median number of thrombectomy device passes was 2 (IQR: 1–2). The median NIHSS score after thrombectomy was 23.50 (IQR: 12.25–27.00). In 2 patients, because of severe arterial stenosis, the Solitaire stent was released after balloon PTA without retrieval. The recanalization failed in 2 patients because of severe stenosis of the basilar artery and
9
ACCEPTED MANUSCRIPT repeated occlusion after balloon and stent angioplasty. Atherosclerotic stenosis of the basilar artery was found during thrombectomy in 30 patients (83.33%), and angioplasty was performed in 25 of these patients: balloon PTA
RI PT
alone, 8 patients; permanent intracranial stent placement alone, 5 patients; and balloon PTA combined with permanent stenting, 12 patients. Recanalization was successful in 34 patients (94.4%) with TICI grades ≥ 2b; furthermore, 88.9% of these patients
SC
achieved TICI grade 3. The median time between symptom onset and recanalization was 572.50 min (IQR: 473.00–787.50 min). The median door-to-puncture time was 175
Procedure-related complications
M AN U
min (IQR: 113.25–426.75 min; Table 2).
Six cases of SICH (16.67%) related to the acute therapy occurred in the
TE D
perioperative period. During thrombectomy, difficulty in retrieving the Solitaire stent was encountered in 1 patient, and the stent was released.
EP
Clinical outcomes
All the patients were followed up. The mortality rate was 30.56% (11/36) on day 90
AC C
of follow-up. Favorable outcomes (mRS scores: 0–2) were achieved in 10 patients, which represented 27.8% of all patients and 40.0% of the survivors (recanalization was successful in all 10 of these patients).
Predictive factors for clinical outcomes On univariate analysis, poor outcomes (mRS score > 2) were associated with pre-thrombectomy unconsciousness (P = 0.017, 95% confidence interval [CI]:
10
ACCEPTED MANUSCRIPT 2.44–9.10), pre-thrombectomy GCS score (P = 0.006, odds ratio [OR]: 0.68, 95% CI: 0.50–0.930), onset-to-recanalization time > 10.5 h (P = 0.022, OR: 12.27, 95% CI: 1.35–111.61), residual stenosis (P = 0.021, OR: 1.04, 95% CI: 1.00–1.08), and
RI PT
post-thrombectomy NIHSS score (P < 0.001, OR: 1.51, 95% CI: 1.12–2.03). Hyperglycemica (P = 0.070) and diabetes mellitus (P = 0.069) tended to be associated with poor clinical outcome, but the association did not reach statistical significance.
SC
Further analysis showed that pre-thrombectomy unconsciousness was associated with pre-thrombectomy GCS score (P < 0.001) and post-thrombectomy NIHSS score (P <
M AN U
0.001). Residual stenosis was associated with angioplasty (P = 0.015) and puncture-to-recanalization time (P = 0.017; Table 3).
We further calculated the cutoff value of the pre-thrombectomy GCS score and post-thrombectomy NIHSS score for predicting a poor outcome, by using the χ2 test or
TE D
Fisher exact test. A pre-thrombectomy GCS score of less than 8 and post-thrombectomy NIHSS score of greater than 28 predicted a poor clinical outcome.
EP
Predictive factors for mortality
On univariate analysis, mortality (death) was associated with age ≥ 60 years (P =
AC C
0.028, OR: 5.67, 95% CI: 1.18–27.25), pre-thrombectomy GCS score (P = 0.007, OR: 0.65, 95% CI: 0.46–0.92), post-thrombectomy NIHSS score (P < 0.001, OR: 1.71, 95% CI: 1.08–2.71), and recanalization without SICH (P = 0.018, OR: 0.10, 95% CI: 0.02–0.68). Baseline glycemia (P = 0.074), door-to-puncture time (P = 0.068), pre-thrombectomy mRS score (P = 0.059), and post-thrombectomy SICH (P = 0.057) tended to be associated with mortality, but did not reach statistical significance (Table 4).
11
ACCEPTED MANUSCRIPT We further calculated the cutoff value of pre-thrombectomy GCS scores and post-thrombectomy NIHSS scores for predicting mortality, by using the χ2 test or Fisher exact test. A pre-thrombectomy GCS score of less than 6 and post-thrombectomy
RI PT
NIHSS score of greater than 12 predicted high mortality.
DISCUSSION
SC
Endovascular therapy with a stent retriever is now recommended as the first choice of treatment in selected patients with large-artery occlusion involving the anterior
M AN U
cerebral circulation15-20. However, few randomized controlled trials have focused on the safety and effectiveness of mechanical thrombectomy for the posterior circulation, and only a few small-sample studies on mechanical thrombectomy have focused on ABAO 8-12, 21-23
. Roth et al.9 analyzed 12 patients with ABAO treated using Penumbra (a device
TE D
for aspiration thrombectomy) and intravenous thrombolysis. Andersson et al.8 examined 28 cases of ABAO treated using different clot retrievers and supplemental therapies such as intra-arterial thrombolysis and balloon angioplasty. Mordasini et al.10 treated 14
EP
ABAO patients with the Solitaire FR device. All 14 of these patients successfully underwent recanalization (TICI grades: 2b–3), and the mean number of passes was 1.3.
AC C
There was no symptomatic intracranial hemorrhage. At the 3-month follow-up, 28.6% patients (4/14) had achieved good functional outcomes (mRS scores: 0–2), and the total mortality was 35.7% (5/14). Espinosa et al.11 evaluated 18 patients with vertebrobasilar occlusion treated with a stent retriever, and reported that recanalization was successful in 94.4% patients (17/18; TICI grades: 2b–3). In addition, 50% of these patients (9/17) had good functional outcomes (mRS scores: 0–2). No symptomatic intracranial hemorrhage occurred, and the mortality rate was 22.2% (5/17). In a recent study,
12
ACCEPTED MANUSCRIPT Mourand et al.12 evaluated 31 ABAO patients treated with the Solitaire device within 24 h after symptom onset. Recanalization was successful in 23 of these patients (74%; TICI grades, 2b–3), and favorable outcomes (mRS scores: 0–2) were achieved in 35% of the
RI PT
patients (11/31). The total mortality rate was 32% (10/31). Mohlenbruch et al.21 evaluated 24 ABAO patients treated with the Solitaire FR or Revive SE device (Codman, US). Recanalization was successful in 18 of these patients (75%; TICI grades:
SC
2b–3), with a mortality of 29% (7/24) during the first 3 months. Favorable clinical outcomes (mRS scores: 0–2) were obtained in 8 patients (33%) after 3 months. Wang et
M AN U
al.22 studied 18 ABAO patients who underwent arterial interventional treatment with a recanalization rate of 94.4%. The average number of passes was 1.5, and the total mortality rate was 27.8% (5/18). Good prognoses were achieved in 38.9% patients. A recent study has also reported successful stent retrieval in children with ABAO23.
TE D
Recently a systematic review and meta-analysis found that Stent retriever thrombectomy achieves a high rate of recanalization and functional independence while being relatively safe for patients with BAO24.
EP
Approximately 26%–36% of ABAO patients have associated atherosclerotic lesions10. However, the main cause of ABAO in our population was atherothrombotic
AC C
occlusion, which was present in 91.67% patients (33/36), and this percentage was significantly higher than those reported in other studies (16%–29.2%)12, 21. Thrombi originating from ulcerated atherosclerotic plaques are usually stickier than embolic thrombi, which make the former more difficult to retrieve10. When compared with complete recanalization, partial recanalization of vessels with atherothrombotic lesions is more likely to be associated with reocclusion after stent retrieval, with reported reocclusion rates of 10%–30% after intra-arterial thrombolysis25, 26.
13
ACCEPTED MANUSCRIPT The rate of stenosis of the occluded artery was 83.33% (30/36) among the ABAO patients in our series, and 25 (69.4%) of these patients underwent angioplasty. The stenosis rate in our study is higher than the rates reported in previous studies. Many
RI PT
studies27-30 have reported the use of balloon PTA and intracranial stenting during the process of thrombolysis or thrombectomy in patients with vascular stenosis. These measures yielded recanalization rates of 70%–94%, which are higher than the rates
SC
achieved with intravenous or intra-arterial thrombolysis alone27-30. In our study, the rate of successful recanalization was 94.44% (34/36), which is comparable to that obtained
M AN U
in other series8-12, 21. In our study, when stenosis led to partial recanalization, balloon PTA and/or permanent intracranial stent implantation was performed an additional measure if there was inadequate distal perfusion, or if new thrombus formation or reocclusion was noted at the site of residual stenosis. Our previous experience has
TE D
shown that the combined use of mechanical thrombectomy with angioplasty and stent placement for ABAO with severe underlying intracranial atherosclerotic stenosis is technically feasible and safe14.
EP
The mean thrombectomy time with the SolitaireTM device in our series was lower (no statistically significant) than that obtained with the MERCITM device (105 min vs.
AC C
139 min); in addition, the mean retrieval times were lower with former than with the latter (1.7 times vs. 3 times)12. The high angioplasty rate made our thrombectomy procedure more time consuming. Therefore, the procedure time in our series involving the Solitaire device was greater than that reported in a recent study of thrombectomy in the posterior circulation (105 min vs. 61 min)12. Our results showed that SolitaireTM thrombectomy could effectively restore blood flow after ABAO and improve clinical outcomes. The rates of favorable outcomes (30%
14
ACCEPTED MANUSCRIPT vs. 20%–24%) and mortality (30% vs. 50%–56%) were better (no statistically significant) in our study than in previously reported studies of intravenous or intra-arterial thrombolysis2, 31. All these results indicated the technical feasibility and
RI PT
applicability of mechanical thrombectomy using stent retrieval to treat ABAO. However, despite the high rate of successful recanalization, the rate of favorable clinical outcomes was limited.
SC
In addition to successful recanalization, certain factors have been reported to predict clinical outcomes. In our study, we evaluated other predictors of clinical
M AN U
outcomes. Considering the high stenosis rate in our series, we recorded the rate of residual stenosis of the responsible artery after thrombectomy. Inconsistent with previous studies, we found that a higher residual stenosis rate was associated with poor clinical outcomes at 90 days (P = 0.021). It was more difficult to perform stent
TE D
thrombectomy in ABAO patients with severe arterial stenosis. Sometimes, the stent could not be passed through the stenosed artery without using balloon PTA. We also found that a higher residual stenosis rate was associated with angioplasty (P = 0.015).
residual
EP
This is because angioplasty was performed for ABAO patients with severe stenosis, and stenosis
was
common
even
after
angioplasty.
The
mean
AC C
puncture-to-recanalization time was longer (no statistically significant) in patients who underwent angioplasty than in those who did not undergo angioplasty (111 min vs. 91 min). We found that the residual stenosis rate was also associated with the puncture-to-recanalization time (P = 0.017). Taken together, our study included more atherosclerotic ABAO patients, and most of them required balloon PTA and/or stent placement for angioplasty, which might have caused additional complications, increased the operation time, and affected the clinical outcomes. Moreover, the degree of residual
15
ACCEPTED MANUSCRIPT stenosis might be related to the perfusion of the ischemic territory, and milder stenosis might be associated with better distal perfusion and better outcomes25,
26
. Thus, a
decrease in residual stenosis and in thrombectomy time was beneficial in ABAO
RI PT
patients. Besides the residual stenosis rate, pre-thrombectomy unconsciousness (P = 0.017), low pre-thrombectomy GCS score (P = 0.006), and high post-thrombectomy NIHSS
SC
score (P < 0.001) were associated with poor clinical outcomes. These three parameters were key factors reflecting the clinical status of the patients. Further analysis showed
M AN U
that pre-thrombectomy unconsciousness was associated with low pre-thrombectomy GCS scores (P < 0.001) and high post-thrombectomy NIHSS score (P < 0.001). Thus, we concluded that it is reasonable to predict clinical outcomes on the basis of consciousness status and neurological scores.
TE D
Another important factor affecting clinical outcome was the onset-to-recanalization time. Early recanalization has been significantly associated with better clinical outcomes 15, 32. The positive effect of early recanalization in the MR CLEAN trial was
EP
time-dependent, with the adjusted common OR decreasing from 3.0 (95% CI: 1.6–5.6) at an onset-to-recanalization time of 3.5 h, to 1.5 (95% CI: 1.1–2.2) at 6 h15. The
AC C
treatment effect was not statistically significant anymore when reperfusion was achieved after 6 h and 19 m. The benefit of thrombectomy was also shown to be time-dependent in the IMS III trial, where an increased time to reperfusion was associated with a decreased probability of a good functional outcome (adjusted relative risk for every 30-min delay: 0.88, 95% CI: 0.80–0.98)33. We found that a cutoff onset-to-recanalization time of 10.5 h was related with poor outcomes. Patients in whom the onset-to-recanalization time was more than 10.5 h had a higher rate of poor
16
ACCEPTED MANUSCRIPT outcomes (57.7%) than patients who underwent early recanalization (<10.5 h; 10%). Recently, Mourand et al.12 reported an association between elevated baseline glucose (P = 0.008) and poor outcomes (mRS score > 2). We found that patients with high baseline
RI PT
glucose (P = 0.070) and diabetes (P = 0.069) tended to have poor outcomes. This may be because patients with diabetes tended to have higher baseline glucose levels after ABAO (P = 0.064), and glucose control is important in AIS patients.
SC
The risk factors of mortality were also analyzed using our data. We found that age ≥ 60 years (P = 0.028), low pre-thrombectomy GCS score (P = 0.007), and high
M AN U
post-thrombectomy NIHSS score (P < 0.001) were associated with mortality. Baseline glycemia (P = 0.074), door-to-puncture time (P = 0.068), pre-thrombectomy mRS score (P = 0.059), and post-thrombectomy SICH (P = 0.057) tended to be associated with mortality. Thus, age and neurological scores could help predict mortality; however,
TE D
these factors are unmodifiable. The most important modifiable risk factors were those related to thrombectomy. We further found that successful recanalization without SICH was significantly associated with survival (P = 0.018). Thus, a high recanalization rate
EP
with low SICH was the objective of thrombectomy. With regard to hemorrhagic complications, the rate of SICH related to the
AC C
procedure was acceptable at 16.67% (6/36). However, this rate was higher than those reported with intravenous or intra-arterial thrombolysis alone2, 31, 34 but was comparable to those obtained with other interventions3, 35, 36. In our study, four of the patients with SICH died, and the other 2 had severe neurological dysfunction. One of these patients had been previously treated with intravenous thrombolysis, and in 2 patients, the hemorrhage was related to the manipulation during mechanical thrombectomy. Difficulty in retrieving the Solitaire stent was encountered in 1 patient, in whom the
17
ACCEPTED MANUSCRIPT stent was released in position. However, the stenosis was too severe for recanalization with the Solitaire stent, and a balloon expandable stent was deployed for angioplasty, which led to successful recanalization.
RI PT
In 2 patients, basilar artery reocclusion occurred after recanalization. In 1 patient, reocclusion occurred 4 days after the Solitaire thrombectomy and stent angioplasty because of incompliance with the dual antiplatelet therapy. Emergency angiography was
SC
performed in this patient, and the basilar artery was successfully recanalized again by using intra-arterial thrombolysis combined with balloon PTA. In the other patient,
M AN U
reocclusion occurred 2 months after SolitaireTM thrombectomy because of 50% residual stenosis; in this patient, repeat recanalization was performed using stent angioplasty. In our series, we found a high rate of recanalization and favorable outcomes in ABAO patients treated with Solitaire stent thrombectomy, even though there were
TE D
hemorrhagic and ischemic complications. There are certain limitations to our study, which focused on a very specific population. The number of patients in our study was relatively small, and the study had limited statistical power despite the fact that this is
EP
one of the largest stent retrieval series in Asian ABAO patients. In future, we intend to undertake a randomized controlled trial on this topic to better evaluate the effects of
AC C
endovascular thrombectomy in ABAO patients.
Conclusion
Solitaire thrombectomy resulted in a high recanalization rate in ABAO patients,
with favorable clinical outcomes in approximately one-third of patients. Intracranial stenosis was the main cause of ABAO, and angioplasty was commonly performed during mechanical thrombectomy for better recanalization and prognosis. The technical
18
ACCEPTED MANUSCRIPT outcomes of patients with ABAO can be improved by avoiding hemorrhagic complications and decreasing the residual stenosis rate. Early recanalization and relatively good pre-thrombectomy status predict favorable outcomes. More, large,
predictive factors for clinical outcomes. References
5.
6.
7.
8.
9. 10.
11.
12. 13.
14.
15. 16.
SC
M AN U
4.
TE D
3.
EP
2.
Schonewille WJ, Algra A, Serena J. Outcome in patients with basilar artery occlusion treated conventionally Journal of neurology, neurosurgery, and psychiatry. 2005; 76: 1238-1241. Lindsberg PJ, Mattle HP Therapy of basilar artery occlusion: a systematic analysis comparing intra-arterial and intravenous thrombolysis Stroke; a journal of cerebral circulation. 2006; 37: 922-928. Eckert B, Kucinski T, Pfeiffer G. Endovascular therapy of acute vertebrobasilar occlusion: early treatment onset as the most important factor Cerebrovascular diseases. 2002; 14: 42-50. Lutsep HL, Rymer MM, Nesbit GM Vertebrobasilar revascularization rates and outcomes in the MERCI and multi-MERCI trials Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 2008; 17: 55-57. Costalat V, Machi P, Lobotesis K. Rescue, combined, and stand-alone thrombectomy in the management of large vessel occlusion stroke using the solitaire device: a prospective 50-patient single-center study: timing, safety, and efficacy Stroke; a journal of cerebral circulation. 2011; 42: 1929-1935. Roth C, Papanagiotou P, Behnke S. Stent-assisted mechanical recanalization for treatment of acute intracerebral artery occlusions Stroke; a journal of cerebral circulation. 2010; 41: 2559-2567. Castano C, Dorado L, Guerrero C. Mechanical thrombectomy with the Solitaire AB device in large artery occlusions of the anterior circulation: a pilot study Stroke; a journal of cerebral circulation. 2010; 41: 1836-1840. Andersson T, Kuntze Soderqvist A, Soderman M. Mechanical thrombectomy as the primary treatment for acute basilar artery occlusion: experience from 5 years of practice Journal of neurointerventional surgery. 2013; 5: 221-225. Roth C, Mielke A, Siekmann R. First experiences with a new device for mechanical thrombectomy in acute basilar artery occlusion Cerebrovascular diseases. 2011; 32: 28-34. Mordasini P, Brekenfeld C, Byrne JV. Technical feasibility and application of mechanical thrombectomy with the Solitaire FR Revascularization Device in acute basilar artery occlusion AJNR. American journal of neuroradiology. 2013; 34: 159-163. Espinosa de Rueda M, Parrilla G, Zamarro J. Treatment of acute vertebrobasilar occlusion using thrombectomy with stent retrievers: initial experience with 18 patients AJNR. American journal of neuroradiology. 2013; 34: 1044-1048. Mourand I, Machi P, Milhaud D. Mechanical thrombectomy with the Solitaire device in acute basilar artery occlusion Journal of neurointerventional surgery. 2014; 6: 200-204. Miao Z, Song L, Liebeskind DS. Outcomes of tailored angioplasty and/or stenting for symptomatic intracranial atherosclerosis: a prospective cohort study after SAMMPRIS Journal of neurointerventional surgery. 2015; 7: 331-335. Gao F, Lo WT, Sun X. Combined Use of Mechanical Thrombectomy with Angioplasty and Stenting for Acute Basilar Occlusions with Underlying Severe Intracranial Vertebrobasilar Stenosis: Preliminary Experience from a Single Chinese Center AJNR. American journal of neuroradiology. 2015 Berkhemer OA, Fransen PS, Beumer D. A randomized trial of intraarterial treatment for acute ischemic stroke The New England journal of medicine. 2015; 372: 11-20. Goyal M, Demchuk AM, Menon BK. Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke The New England journal of medicine. 2015
AC C
1.
RI PT
prospective, multicenter studies with the Solitaire device are needed to identify
19
ACCEPTED MANUSCRIPT
23. 24.
25. 26.
27.
28.
29.
30. 31. 32.
33.
34.
35.
36.
RI PT
22.
SC
21.
M AN U
20.
TE D
19.
EP
18.
Saver JL, Goyal M, Bonafe A. Stent-Retriever Thrombectomy after Intravenous t-PA vs. t-PA Alone in Stroke The New England journal of medicine. 2015 Campbell BC, Mitchell PJ, Kleinig TJ. Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection The New England journal of medicine. 2015 Jovin TG, Chamorro A, Cobo E. Thrombectomy within 8 Hours after Symptom Onset in Ischemic Stroke The New England journal of medicine. 2015 Powers WJ, Derdeyn CP, Biller J. 2015 AHA/ASA Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association Stroke; a journal of cerebral circulation. 2015 Mohlenbruch M, Stampfl S, Behrens L. Mechanical thrombectomy with stent retrievers in acute basilar artery occlusion AJNR. American journal of neuroradiology. 2014; 35: 959-964. Wang L, Shi W, Su Z. Endovascular treatment of severe acute basilar artery occlusion Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2015; 22: 195-198. Savastano L, Gemmete JJ, Pandey AS. Acute ischemic stroke in a child due to basilar artery occlusion treated successfully with a stent retriever Journal of neurointerventional surgery. 2015 Phan K, Phan S, Huo YR. Outcomes of endovascular treatment of basilar artery occlusion in the stent retriever era: a systematic review and meta-analysis Journal of neurointerventional surgery. 2015 Becker KJ, Monsein LH, Ulatowski J. Intraarterial thrombolysis in vertebrobasilar occlusion AJNR. American journal of neuroradiology. 1996; 17: 255-262. Zeumer H, Freitag HJ, Zanella F. Local intra-arterial fibrinolytic therapy in patients with stroke: urokinase versus recombinant tissue plasminogen activator (r-TPA) Neuroradiology. 1993; 35: 159-162. Jung S, Mono ML, Fischer U. Three-month and long-term outcomes and their predictors in acute basilar artery occlusion treated with intra-arterial thrombolysis Stroke; a journal of cerebral circulation. 2011; 42: 1946-1951. Kashiwagi J, Kiyosue H, Hori Y. Endovascular recanalization of acute intracranial vertebrobasilar artery occlusion using local fibrinolysis and additional balloon angioplasty Neuroradiology. 2010; 52: 361-370. Chandra RV, Law CP, Yan B. Glasgow coma scale does not predict outcome post-intra-arterial treatment for basilar artery thrombosis AJNR. American journal of neuroradiology. 2011; 32: 576-580. Yu YY, Niu L, Gao L. Intraarterial thrombolysis and stent placement for acute basilar artery occlusion Journal of vascular and interventional radiology : JVIR. 2010; 21: 1359-1363. Smith WS Intra-arterial thrombolytic therapy for acute basilar occlusion: pro Stroke; a journal of cerebral circulation. 2007; 38: 701-703. Qureshi AI, Abd-Allah F, Aleu A. Endovascular treatment for acute ischemic stroke patients: implications and interpretation of IMS III, MR RESCUE, and SYNTHESIS EXPANSION trials: A report from the Working Group of International Congress of Interventional Neurology Journal of vascular and interventional neurology. 2014; 7: 56-75. Khatri P, Yeatts SD, Mazighi M. Time to angiographic reperfusion and clinical outcome after acute ischaemic stroke: an analysis of data from the Interventional Management of Stroke (IMS III) phase 3 trial Lancet neurology. 2014; 13: 567-574. Lindsberg PJ, Soinne L, Tatlisumak T. Long-term outcome after intravenous thrombolysis of basilar artery occlusion JAMA : the journal of the American Medical Association. 2004; 292: 1862-1866. Nagel S, Schellinger PD, Hartmann M. Therapy of acute basilar artery occlusion: intraarterial thrombolysis alone vs bridging therapy Stroke; a journal of cerebral circulation. 2009; 40: 140-146. Raphaeli G, Eichel R, Ben-Hur T. Multimodal reperfusion therapy in patients with acute basilar artery occlusion Neurosurgery. 2009; 65: 548-552; discussion 552-543.
AC C
17.
20
ACCEPTED MANUSCRIPT
Table 1. Summary of Patient Characteristics Value 36 30(83.3) 58.6(8.10)
SC
RI PT
28(77.7) 23(63.9) 25(69.4) 12(33.3) 2(5.6) 4(11.1) 33(91.7) 9.80 (4.87) 149.00(135.25-173.75) 5(5-5) 25.50 (21.00-29.00) 8.00(5.00-9.75)
AC C
EP
TE D
M AN U
Characteristics Number of patients Male sex (%) Age (yr) , mean (SD) Past history, n (%) Smoke Drink Hypertension Diabetes Atrial fibrillation TIA Pre-thrombectomy unconsciousness, n (%) Baseline glycemia (mmol/l), mean (SD) Admission SBP (mmHg), median (IQR) Pretreatment mRS score, median (IQR) Pretreatment NIHSS score, median (IQR) Pretreatment GCS score, median (IQR) Stroke type, n (%) Atherosclerosis Cardioembolism Thrombogenesis Stenosis of occlusion artery, n (%)
1
33 (91.7) 2(5.6) 1(2.8) 30(83.3)
ACCEPTED MANUSCRIPT
Table 2. Summary of Treatment, and Outcome Value 274.50(112.25-605.00) 175.00(113.25-426.75) 90.00(60.00-125.00) 572.50(473.00-787.50)
GP IIb/IIIa inhibitor given, n (%)
13(36.1)
Angioplasty, n (%) Balloon PTA Stent PTA+Stent Retrieval times, median (IQR) TICI, n (%) 0 2b 3
25(69.4) 8(22.2) 5(13.9) 12(33.3) 2(1-2)
SC
2(5.6) 11(30.6)
RI PT
Characteristics Onset-to-door time, median (IQR) Door-to-puncture time, median (IQR) Puncture-to-recanalization time, median (IQR) Onset-to-recanalization, median (IQR) Combined tPA, n (%) IV tPA IA tPA
M AN U
2(5.6) 2(5.6) 32(88.9)
Stenosis rate post thrombectomy and angioplasty mean 26.0% median 20.0%
AC C
EP
TE D
Post-treatment NIHSS score, median (IQR) sICH, n (%) mRS at 90 days, n (%) 0 1 2 3 4 5 6 mRS 0-2 at 90 days, n (%) Mortality at 90 days, n (%)
2
23.50(12.25-27.00) 6(16.7) 5(13.9) 1 4 6 3 6 11 10(27.8) 11(30.6)
ACCEPTED MANUSCRIPT
Table 3. Risk factors for clinical outcome value 38.9%
n 12
Pre-thrombectomy Unconsciousness Baseline glycemia (mmol/l), mean (SD) Diabetes mellitus Pre-thrombectomy GCS score, median (IQR) Pre-thrombectomy mRS score, median (IQR) Angioplasty Residual stenosis (%), mean (SD) Puncture-to-recanalization time, median (IQR) Onset-to-recanalization time > 10.5 h Post-thrombectomy NIHSS score, median (IQR) sICH
33 36 12 36 36 25 36 34 16 36 6
91.7% 9.80 (4.87) 33.3% 8.00(5.00-9.75) 5.00(5.00-5.00) 69.4% 25.97(28.10) 90.00(60.00-125.00) 44.4% 23.50(12.25-27.00) 16.7%
26 26 11 26 26 19 26 26 15 26 6
100.0% 10.71(5.09) 42.3% 6.00(5.00-8.25) 5.00(5.00-5.00) 73.1% 31.35(29.91) 90.00(70.50-135.00) 57.7% 26.00(21.75-30.00) 23.1%
Favorable Outcome (mRS≤ ≤2) △ n value 4 40.0%
p Value*
Raw OR (95%CI)
0.519
1.29(0.29-5.66)
7 10 1 10 10 6 10 8 1 10 0
0.017* 0.070 0.069 0.006* 0.420 0.353 0.021* 0.358 0.022* <0.001* 0.118
M AN U
SC
RI PT
age≥60
n 16
Poor Outcome (mRS>2) △ value 46.2%
All patients
70.0% 7.43(3.43) 10.0% 9.50(7.25-12.50) 5.00(4.75-5.00) 60.0% 12(16.87) 87.00(53.50-127.50) 10.0% 8.50(5.25-12.5) 0.0%
#
/ (2.44-9.10) 1.29(0.96-1.73) 6.60(0.73-60.02) 0.68(0.50-0.93) 1.70(0.66-4.41) 1.81(0.39-8.39) 1.04(1.00-1.08) 1.00 12.27 (1.35-111.61) 1.51(1.12-2.03) 1.30(1.05-1.61)
AC C
EP
TE D
*p Values from Student t test or Wilcoxon rank sum test for continuous variables and the χ2 test or Fisher exact for categorical variables. # OR from logistic analysis. △ Percentage by group (poor and favorable outcome). GCS, Glasgow Coma Scale; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; sICH, symptomatic Intracranial Hemorrhage.
3
ACCEPTED MANUSCRIPT
Death △ Value 72.7% 100.0% 11.98(6.31) 45.5% 5.00(3.00-6.00) 5.00(5.00-5.00) 63.6% 28.64(33.02) 97.50(76.50-127.50) 30.00(26.00-35.00) 36.4% 90.9% 54.5%
SC
n 8 11 11 5 11 11 7 11 10 11 4 10 6
M AN U
age≥60 Pre-thrombectomy unconsciousness Baseline glycemia (mmol/l), mean (SD) Diabetes mellitus Pre-thrombectomy GCS score, median (IQR) Pre-thrombectomy mRS score, median (IQR) Angioplasty Residual stenosis (%), mean (SD) Puncture-to-Recanalization time, median (IQR) Post-thrombectomy NIHSS score, median (IQR) sICH Recanalization Recanalization without sICH
n 16 33 36 12 36 36 25 36 34 36 6 34 29
RI PT
Table 4. Risk factors for mortality All patients Value 38.9% 91.7% 9.80 (4.87) 33.3% 8.00(5.00-9.75) 5(5-5) 69.4% 25.97(28.10) 90.00(60.00-125.00) 23.50(12.25-27.00) 16.67% 94.4% 80.6%
n 8 22 25 7 25 25 18 25 24 25 2 24 23
Survival △ Value 32.0% 88.0% 8.84(5.95-11.12) 28.0% 8.00(6.00-10.50) 5.00(5.00-5.00) 72.0% 24.80(26.32) 90.00(60.00-135.00) 18.00(9.50-24.00) 8.0% 96.0% 92.0%
#
p Value*
Raw OR (95%CI)
0.028* 0.322 0.074 0.259 0.007* 0.059 0.449 0.712 0.857 <0.001* 0.057 0.524 0.018*
5.67(1.18-27.25) / (1.18-1.91) 1.14(0.98-1.33) 2.14(0.49-9.35) 0.65(0.46-0.92) / 0.68(0.15-3.07) 1.01(0.98-1.03) 1(0.99-1.01) 1.71(1.08-2.71) 6.57(0.99-43.78) 0.42(0.02-7.34) 0.10(0.02-0.68)
AC C
EP
TE D
*p Values from Student t test or Wilcoxon rank sum test for continuous variables and the χ2 test or Fisher exact for categorical variables. # OR from logistic analysis. △ Percentage by group (Death and survival). GCS, Glasgow Coma Scale; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; sICH, symptomatic Intracranial Hemorrhage.
4
AC C
EP
TE D
M AN U
SC
Abbreviations: ABAO=Acute basilar artery occlusion; BAO=basilar artery occlusion; CTA=Computed tomography angiography; DSA= Digital subtraction angiography; DWI=Diffusion Weighted Imaging; GCS= Glasgow coma scale; GFR=Glomerular Filtration Rate; IQR= Inter Quartile Range; IRB=Institutional Review Board; MRA=Magnetic resonance angiography; mRS= modified Rankin Scale; NIHSS=National Institutes of Health Stroke Scale; PTA=Percutaneous transluminal angioplasty; sICH= symptomatic intracranial hemorrhage; TICI= Thrombolysis in Cerebral Ischemia Scale;
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
Highlights: SolitaireTM thrombectomy resulted in a high recanalization rate for ABAO and the clinical outcome was favorable in about one-third of
RI PT
patients. Intracranial stenosis was main reason for ABAO and angioplasty was commonly performed during mechanical thrombectomy for a better recanalization and prognosis in China.
SC
The technical outcomes of patients with ABAO could be improved by avoiding hemorrhagic complications and decreasing residual stenosis
M AN U
rate.
Early recanalization and better pre-thrombectomy status predicts a
AC C
EP
TE D
better outcome.