Background and purpose The optimal treatment for patients with acute stroke refractory to stent-based thrombectomy (SBT) is unclear. This study aimed to report clinical outcomes of manual aspiration thrombectomy (MAT) for the treatment of acute ischemic stroke refractory to SBT.
Methods We retrospectively analyzed clinical and angiographic data of 30 patients who underwent MAT with a Penumbra reperfusion catheter because of refractory occlusion after SBT with a Solitaire stent as first-line endovascular therapy. Refractory occlusion was defined by a lack of successful revascularization (defined as Thrombolysis In Cerebral Infarction ≥2b) after five retrieval attempts. A good outcome was defined as a modified Rankin scale score of ≤2 at 3 months.
Results Successful revascularization was achieved in 83.3% (25/30) of the patients who underwent MAT after failed SBT. There was no arterial rupture or dissection or symptomatic intracranial hemorrhage. Two embolic occlusions in a new arterial territory and five subarachnoid hemorrhages occurred, neither of which caused neurological worsening. At the 3-month follow-up, 36.7% (11/30) of patients exhibited a good outcome. The mortality rate was 6.7% (2/30) at 3 months.
Conclusions This study suggests that MAT with the Penumbra reperfusion catheter can further increase the revascularization rate without serious complications in patients with acute stroke with refractory occlusions after SBT with a Solitaire stent.
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Mechanical thrombectomy with a stent-type thrombectomy device is increasingly used as first-line endovascular therapy for the treatment of acute ischemic stroke secondary to an intracranial large vessel occlusion. Randomized controlled trials and several case series have demonstrated the efficacy of stent-based thrombectomy (SBT) in the recanalization of occluded cerebral arteries.1–4 However, failure of SBT to achieve successful revascularization has been reported in 20–30% of treated cases.1–4 Rescue therapy for patients with an intracranial large vessel occlusion refractory to SBT include the use of an alternative mechanical device, intra-arterial thrombolysis, or mechanical clot disruption with a micro-guidewire.1–3 Manual aspiration thrombectomy (MAT) using a flexible aspiration catheter is another mechanical thrombectomy technique for treating acute ischemic stroke.5–7 Recent studies suggest that MAT with the newest generation of large-bore aspiration catheters is a promising technique that can reduce procedure times and provide superior cost-effective value, with primary revascularization rates similar to SBT.8 ,9 Applying a different thrombectomy technique such as MAT may be a solution for persistent arterial occlusions in cases of failed SBT, but this treatment strategy has not yet been studied systematically.
Since 2011 we have decided to perform SBT with a Solitaire stent (Covidien/ev3, Irvine, California, USA) as a first-line revascularization approach in all acute stroke interventions based on our preliminary experience, which showed better revascularization rates in patients receiving SBT than those receiving MAT with a Penumbra reperfusion catheter (Penumbra, Alameda, California, USA). MAT was attempted as a rescue approach if SBT failed. In addition, we thought that the clot may be kept intact for subsequent mechanical revascularization approaches when SBT failed, whereas MAT may break the clot into smaller pieces which makes it more difficult to use subsequent approaches such as SBT following failure of MAT. The aim of this study was to report clinical outcomes of MAT with a Penumbra reperfusion catheter in patients with acute stroke refractory to SBT with a Solitaire stent.
Materials and methods
From January 2011 to May 2013, 30 patients with acute ischemic stroke caused by intracranial large artery occlusion were treated with MAT using a Penumbra reperfusion catheter as second-line endovascular therapy after failure of the SBT. This retrospective study analyzed clinical and angiographic data from these 30 patients. During the same period, 163 consecutive patients were treated with SBT using the Solitaire stent as first-line endovascular therapy.
Upon admission, neurological assessments were performed by a stroke neurologist based on the National Institutes of Health Stroke Scale (NIHSS). All patients underwent a non-enhanced cranial CT scan and multimodal MRI before endovascular treatment. The inclusion criteria for endovascular therapy were: baseline NIHSS score ≥4; no intracerebral hemorrhage detected on the cranial CT or MRI; major arterial occlusion detected with MR angiography and catheter angiography; a target mismatch pattern on multimodal MRI based on visual estimation (time to peak map of perfusion imaging showing a lesion volume ≥30% larger than that detected with diffusion-weighted imaging (DWI)) for an anterior circulation stroke; infarct volume on the DWI or non-enhanced CT less than one-third of the middle cerebral artery (MCA) territory for anterior circulation stroke; and no bilateral diffuse pontine ischemia on the DWI for posterior circulation stroke.
Eligible patients who met the standard National Institute of Neurological Disorders and Stroke (NINDS) criteria for intravenous recombinant tissue plasminogen activator (rtPA) were initially treated with 0.9 mg/kg intravenous rtPA. Subsequent endovascular therapy was considered within 1 h of intravenous rtPA for patients with no neurological improvement, which was defined as an unchanged NIHSS score from baseline or a worsening neurological deficit.
All endovascular therapy was performed by one interventional neuroradiologist with 11 years of experience in neurovascular intervention. Cerebral angiography and endovascular therapy were performed under conscious sedation. In cases of agitation, an intravenous bolus of midazolam was given and repeated if necessary. The details of the technique for SBT with a Solitaire stent have been described previously.10 Refractory occlusion was defined by a lack of successful revascularization (defined as Thrombolysis In Cerebral Infarction (TICI) ≥2b) after five retrieval attempts.
When the refractory occlusion occurred, additional MAT was performed with a Penumbra reperfusion catheter. The details of the technique for MAT with a Penumbra reperfusion catheter have been described previously.5 A direct manual aspiration technique with a 50 mL syringe without a separator or vacuum pump was used in all patients. We used the 054 Penumbra aspiration catheter for occlusions in the distal intracranial internal carotid artery (ICA) or basilar artery or proximal M1 segment of the MCA, and the 041 catheter for occlusions in the distal M1 or M2 segment of the MCA or MCA bifurcation. When the additional MAT with a Penumbra reperfusion catheter was unsuccessful, low-dose intra-arterial urokinase infusion and clot disruption with a micro-guidewire was performed.
When the patient had a tandem occlusion at the proximal cervical portion of the ICA, carotid angioplasty and stenting were performed prior to intracranial mechanical thrombectomy. If an underlying atherosclerotic stenosis was revealed during the procedure, balloon angioplasty with or without stenting was performed after mechanical thrombectomy. All patients underwent non-enhanced CT scans immediately after and 24 h after endovascular therapy. The start of endovascular therapy was defined as the moment the needle punctured the common femoral artery. Revascularization status was assessed on the final angiogram and classified according to the TICI scale.11 Successful revascularization was defined as TICI grade 2b or 3. Angiographic images were assessed by two experienced neuroradiologists who were blinded to the procedure and decisions were made by consensus.
For all patients we analyzed the medical records to determine age, sex, vascular risk factors, stroke subtype according to TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification, baseline NIHSS score, use of intravenous rtPA, time to endovascular therapy, duration of the procedure, presence or absence of symptomatic intracranial hemorrhage, revascularization status, procedure-related vessel perforation and dissection, NIHSS score at discharge, and clinical outcome. Symptomatic intracranial hemorrhage was defined as any intracranial hemorrhage that caused neurological deterioration (increase of ≥4 points in the NIHSS score or a deterioration of 1 point in the level of consciousness on NIHSS).
Major complications were defined as the following events: any arterial perforation or dissection, symptomatic intracranial hemorrhage, periprocedural mortality, or any other complications causing neurological deterioration. Minor complications were defined as any asymptomatic intracranial hemorrhage within 24 h of the procedure or any other complications without causing neurological deterioration. Neurological evaluation was performed immediately after treatment by a stroke neurologist, then again 24 h and 3 months after treatment, when any change occurred in clinical symptoms, and before the patient was discharged. Clinical outcome was assessed by a stroke neurologist using the modified Rankin scale (mRS) during an outpatient visit 3 months after treatment. If patients were unable to attend the outpatient clinic, outcomes were obtained via telephone interview. A good clinical outcome was defined as an mRS score ≤2.
Statistical analyses were performed with SPSS software V.20.0 (SPSS, Chicago, Illinois, USA). The relationship between the characteristics and 3-month clinical outcome was determined by bivariate analysis. The χ2 test was used for categorical variables and the Mann–Whitney U test for continuous variables. A p value<0.05 was considered significant.
Of the 163 patients treated with mechanical thrombectomy during the study period, 98 patients had occlusions in the MCA, 41 in the ICA, and 24 in the basilar artery. SBT with a Solitaire stent failed to achieve successful revascularization in 21 (21.4%) patients with MCA occlusions, 20 (48.8%) patients with ICA occlusions, and 5 (20.8%) patients with basilar artery occlusions. Of those with MCA occlusions, 11 patients had occlusion in the MCA bifurcation, 6 in the proximal M1 segment, and 4 in the M2 segment. All five patients with basilar artery occlusion had occlusions in the tip of the basilar artery. Intravenous rtPA was administered in 50% (15/30) of patients before endovascular treatment.
Overall, successful revascularization (TICI 2b or 3) with a Solitaire stent alone was achieved in 71.8% (117/163) of patients. Of 46 patients who failed SBT, 30 patients (16 men and 14 women) received MAT with a Penumbra reperfusion catheter as second-line treatment. Sixteen patients did not receive MAT because of distal migration of thrombi (n=14) or device inaccessibility (n=2). The baseline characteristics of the patients according to clinical outcome are shown in table 1.
Successful revascularization was achieved in 83.3% (25/30) of patients and complete revascularization (TICI grade 3) occurred in 56.7% (17/30) of patients. The five patients without successful revascularization had ICA occlusions. Low-dose intra-arterial urokinase infusion and aggressive clot disruption was performed in these five patients, but successful revascularization did not occur. Three patients had underlying atherosclerotic stenosis in the intracranial ICA, and intracranial angioplasty was performed to treat the underlying stenosis without angioplasty-related complication. Carotid stenting was performed in one patient prior to the intracranial revascularization procedure in order to gain access to the target vessel.
At discharge, NIHSS scores were improved (decrease ≥4 points, median 7.5, range 0–16) in 18 patients (60%). At the 3-month follow-up, 11 patients (36.7%) exhibited a good clinical outcome (mRS 0–2). The median NIHSS score at admission tended to be lower in patients with a good outcome than in those with a poor outcome (11 vs 14, p=0.134). Successful recanalization tended to be associated with a good outcome; 44% (11/25) of patients with revascularization had a good outcome whereas none of the patients without revascularization had a good outcome (p=0.062). There was a good outcome in 46.7% (7/15) of patients who did not receive intravenous rtPA and in 26.7% (4/15) of those who received intravenous rtPA; this difference was not statistically significant. Other variables including age, sex, risk factors, stroke subtype, time to treatment, procedure time, and time to reperfusion were not significantly associated with a good outcome.
There were no major complications; no vessel perforation or dissection was observed and no patient experienced symptomatic intracranial hemorrhage during their hospital stay. Minor complications were observed in seven patients (23.3%); two embolic occlusions occurred in a new arterial territory which did not cause post-procedural neurological worsening and five patients developed subarachnoid hemorrhage (SAH) on the immediate post-treatment CT scan, but these patients exhibited no post-procedural neurological worsening or associated symptomatic parenchymal hemorrhage. The mortality rate was 6.7% (2/30) at 3 months. One patient with occlusion in the cavernous portion of the ICA who had no revascularization (TICI 0) died 58 days after stroke onset because of massive hemispheric infarction and one patient with MCA occlusion who had successful revascularization (TICI 2b) died 88 days after stroke onset because of aspiration pneumonia.
In our study, SBT with a Solitaire stent resulted in a primary rate of revascularization (TICI 2b or 3) of 71.8% (117/163). A recent prospective multicenter study reported a successful revascularization rate (TICI 2b or 3) of 79.2% (160/202).3 Thus, 20–30% of patients with acute stroke treated with SBT are expected to require second-line treatment for refractory occlusion after failed SBT.
The cause of refractory occlusion in patients receiving SBT is unclear. A large clot burden might be one of the main causes of refractory occlusion in our study; 49% of patients with an intracranial ICA occlusion had a refractory occlusion compared with 21% of those with an MCA occlusion. Other causes of a refractory occlusion after SBT might include the mobility of thrombi at arterial bifurcation sites (MCA bifurcation or tip of basilar artery) and arterial tortuosity. In this study, 52% (11/21) of patients with refractory occlusions in the MCA had occlusions in the MCA bifurcation site and 100% (5/5) of those with refractory occlusion in the basilar artery had occlusions in the tip of the basilar artery.
The present study demonstrates that MAT using the Penumbra reperfusion catheter is highly effective for the treatment of refractory occlusion after failed SBT. Successful revascularization (TICI grade 2b or 3) was achieved in 83% (25/30) of patients who were refractory to SBT in the present study, and 44% (11/25) of patients with revascularization had a good outcome. Adding MAT as a second-line treatment increased the overall revascularization rate to 87.1% (142/163) in our patient group. In a prospective multicenter single-arm study, Pereira et al3 reported that the primary revascularization rate with a Solitaire stent was 79.2% and the final revascularization rate after rescue therapy increased to 88.1%, which is similar to our results. In their study, rescue therapy consisted of intra-arterial thrombolysis and mechanical thrombectomy. The details of rescue mechanical thrombectomy were not described in their report.
Only a few studies have evaluated the combined use of different mechanical techniques for treating acute ischemic stroke.6 ,9 ,12 ,13 Jankowitz et al6 reported a series of 191 patients with acute stroke who were treated with a Merci retriever in conjunction with MAT using the Distal Access Catheter (Concentric Medical) or Penumbra aspiration catheter. In their study, mechanical thrombectomy with a Merci retriever and MAT were performed simultaneously using a triaxial system. Successful recanalization (TICI 2b or 3) was achieved in 71% of the patients and 54% had a good outcome (mRS 0–2). Lee et al12 reported a series of 10 patients with an acute ICA terminus occlusion who were treated with both SBT with a Solitaire stent and MAT with a Penumbra reperfusion catheter. One of the two thrombectomy techniques was selected as the first-line treatment at the operator's discretion; the rate of TICI 2b or 3 recanalization was 60%, no patients had a good outcome, and the mortality rate was 40%. Kang et al13 described the combined use of MAT and SBT in patients with acute anterior circulation stroke. In contrast to our study, they used MAT with a Penumbra reperfusion catheter as the first-line endovascular treatment and SBT with a Solitaire stent as the second-line endovascular treatment when three MAT attempts failed. The study reported a primary revascularization rate (TICI 2b or 3) of 53% (39/74) with MAT, which is considerably lower than that with SBT in the present study (72%). They reported a recanalization rate of 82.9% (29/35) and a good outcome was achieved in 62.9% (22/35) of patients who were treated with SBT following failed MAT.
Recently, Turk et al9 reported a series of 98 patients who were treated with a combination of MAT and SBT. In their study, MAT was a first approach and was performed using the newest generation of large-bore aspiration catheters (Penumbra MAX or ACE). Additional thrombectomy using stent retrievers was performed if MAT alone failed. Successful revascularization (TICI 2b or 3) with MAT alone was achieved in 78% of cases, which is similar to that achieved in recent SBT studies.1–4 The final successful revascularization rate was 95%. In their study, a good outcome (mRS 0–2) was achieved in only 18% of patients who required rescue SBT or were unsuccessful after MAT, and the mortality rate was 35%.
Rescue treatments other than MAT after failed SBT might include intra-arterial thrombolysis or mechanical clot disruption using a microwire or an angioplasty balloon. However, these therapies have been limited by an increased risk of intracranial hemorrhage and modest revascularization rates. With recent advancement of devices and approaches, both SBT and MAT are now becoming the main treatment options for acute stroke intervention.14
In our cohort of patients we found no variables that were associated with a good outcome at 3 months, except NIHSS score at discharge. Successful revascularization (TICI 2b or 3) tended to be associated with a good outcome at 3 months; 44% (11/25) of patients with revascularization had a good outcome whereas none of the patients without revascularization had a good outcome (p=0.062). The NIHSS score at admission tended to be lower in patients with a good outcome than in those with a poor outcome (11 vs 14, p=0.134). We did not perform logistic regression analysis because the sample size was small.
In our study, no symptomatic intracranial hemorrhage occurred during hospital stay and no arterial rupture or dissection related to mechanical devices occurred. Two embolic occlusions occurred in an ipsilateral anterior cerebral artery territory and five SAHs, neither of which caused post-procedural neurological worsening. None of the patients with SAH received intracranial angioplasty and angiographies obtained during the procedures in these patients revealed no contrast extravasation. Yoon et al10 reported that SAH was not uncommon after SBT with a Solitaire stent, but they seemed to be benign. They speculated that unidentified small arterial ruptures due to mechanical stretch during stent retrieval might have played a role in the development of SAH after SBT.10 In our study the mortality was 6.7% (2/30) at 3 months, which is among the lowest reported in the literature.1–3 ,6
This single-center retrospective study has the limitations inherent in this type of case series, including the small number of patients and its lack of a prospective study design. In addition, the small sample was further divided into subgroups with smaller numbers of patients, which precluded drawing strong conclusions from this study. Successful revascularization tended to be associated with a good outcome in our cohort of patients. However, this trend did not reach statistical significance. Finally, additional interventions including low-dose intra-arterial urokinase infusion and clot disruption with micro-guidewire, intracranial angioplasty, and carotid artery stenting might have affected the outcomes in our study.
In conclusion, the current study suggests that MAT with the Penumbra reperfusion catheter can further increase the revascularization rate without serious complications in patients with acute stroke with refractory occlusions after SBT. Future prospective randomized controlled studies are needed to determine the optimal role of this approach compared with other types of stroke therapy.
Contributors Concept and design: WY, GWJ, HKK. Acquisition of data: SKK, SMM, MSP. Analysis and interpretation of data: WY, SKK, SMM, MSP. Drafting the article: WY, SKK. Revising the article: WY, GWJ, HKK. Final approval: all authors.
Competing interests None.
Ethics approval Chonnam National University Hospital Institutional Review Board approved this retrospective analysis and waived informed consent based on the study design.
Provenance and peer review Not commissioned; externally peer reviewed.