Article Text
Abstract
Background Endovascular treatment of wake-up strokes (WUS) has been previously described, mostly with the use of pharmacological thrombolysis or first generation thrombectomy devices.
Objective To describe outcomes of WUS treated with modern endovascular therapy since the Food and Drug Administration approval of stent retrievers, and to identify predictors of good clinical outcome in this population of stroke patients.
Methods We performed a multicenter retrospective analysis of consecutive patients with WUS who underwent thrombectomy with stent retrievers Trevo (Stryker, Kalamazoo, Michigan, USA) and Solitaire FR (Covidien, Irvine, California, USA), or primary aspiration thrombectomy. We correlated favorable clinical outcomes with demographic, clinical, and technical characteristics.
Results 52 patients were included in this study; 46 (88%) cases were treated with stent retrievers and 6 (12%) were treated with primary aspiration thrombectomy alone. Successful recanalization (Thrombolysis in Cerebral Infarction (TICI) 2b/3) was achieved in 36 (69%) patients. Favorable clinical outcome at 3 months, defined as a modified Rankin Scale score of 0–2, was achieved in 25 (48%) patients. Duration of intervention <30 min and its success, defined as TICI 2b/3 recanalization, were strong predictors of favorable clinical outcome at 90 days (p<0.001 and p<0.0001, respectively).
Conclusions Our study indicates that endovascular treatment of WUS with stent retrievers and aspiration thrombectomy is safe and effective.
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Introduction
Stroke occurring during sleep with stroke symptoms discovered on awakening is reported in up to 25% of all acute ischemic strokes.1–3 Because of the unclear time of symptom onset, such strokes are typically ineligible for intravenous thrombolysis. With an estimated 795 000 people experiencing a new or recurrent stroke in the USA alone, discovery of alternative treatments for wake-up strokes (WUS) is critically important.4
Endovascular treatment of WUS has been previously described, with studies reporting various degrees of safety and efficacy, mostly with the use of pharmacological thrombolysis or first generation thrombectomy devices.5 Cases of true WUS and strokes with unknown time of symptom onset not related to sleep are often reported together in such series, limiting our ability to accurately estimate the value of catheter based interventions for WUS.5 Also, in light of recent data of improved radiographic and clinical outcomes with modern reperfusion therapies, including stent retriever and primary aspiration thrombectomy over earlier generation therapies, there is a need to evaluate clinical outcomes of WUS treated with endovascular approaches reflective of current practices.6–8
The goal of our study was to describe outcomes of WUS treated with endovascular therapy since the Food and Drug Administration (FDA) approval of stent retrievers, and to identify predictors of good clinical outcome in this population of stroke patients.
Methods
The study was approved by the local institutional review boards at each of the participating centers for retrospective data collection and review. Each participating center retrospectively collected data on consecutive patients with ‘wake-up’ acute ischemic stroke who underwent thrombectomy since the FDA approval of the stent retrievers Trevo (Stryker, Kalamazoo, Michigan, USA) and Solitaire FR (Covidien, Irvine, California, USA). Cases treated with primary aspiration thrombectomy alone using large bore aspiration catheters (Penumbra Inc, Alameda, California, USA) were also included. WUS was defined as stroke occurring during sleep and stroke symptoms discovered on awakening.9 ,10 Patients who received intravenous thrombolysis were excluded from the analysis.
All participating centers had a similar imaging protocol, consisting of non-contrast brain CT followed by CT perfusion (CTP) imaging in combination with craniocervical CT angiography for all patients with suspected acute ischemic stroke, as previously described in detail.11 ,12 Briefly, patients with a third or more of the middle cerebral artery territory infarcted or with ≤50% penumbra were not considered candidates for endovascular treatment.
The following data were collected: demographics, admission National Institutes of Health Stroke Scale (NIHSS) score, time of last known normal before going to sleep, time of symptom discovery on awakening, time of CTP imaging, time of femoral artery puncture, vessels occluded, procedure duration, and procedural technical details. Successful recanalization was defined as a Thrombolysis in Cerebral Infarction (TICI) score of 2b-3. Functional neurologic outcomes were quantified using the modified Rankin Scale (mRS) score at 90 days. Favorable outcome was defined as an mRS score of ≤2. Non-contrast head CT imaging obtained 24–36 h after the intervention was used to assess for hemorrhagic transformation. Intracranial hemorrhage (ICH) was classified as symptomatic if it was associated with worsening of NIHSS score. CT images and angiographic studies to assess ICH and recanalization rates were reviewed by local investigators at each participating site and were not adjudicated by a central core laboratory.
Statistical analysis for each outcome variable analyzed in the present study was performed with SAS statistical software (SAS Institute, Cary, North Carolina, USA). Univariate analysis comparing demographic and clinical factors, treatment details, and outcome was performed using Fisher's exact test for categorical data and a two tailed t test for continuous data. For all statistical analyses, p<0.05 was considered statistically significant.
Results
A total of 52 patients with WUS treated with endovascular therapy since the FDA approval of stent retrievers were identified for inclusion in this study. Stent retriever thrombectomy with the Trevo and Solitaire FR was performed in 46 (88%) cases, and the remaining 6 (12%) cases were treated with primary aspiration thrombectomy alone. Strokes within the anterior circulation were seen in 46 (88%) cases. Successful recanalization (TICI 2b/3) was achieved in 36 (69%) patients. Favorable clinical outcome at 3 months, defined as mRS score 0–2, was achieved in 25 (48%) patients.
Demographic, clinical, and procedural characteristics of the patients with favorable and poor clinical outcomes are shown in table 1. Mean admission NIHSS score was significantly higher in patients with poor outcomes compared with patients with a favorable outcome (17.4±5.1 and 12.7±4.3, respectively; p<0.001). Atrial fibrillation was more frequently seen in patients with poor versus favorable outcomes (52% and 20%, respectively; p=0.02). There was no statistically significant difference in other demographic characteristics or the location of occlusion between the two groups (table 1).
TICI 2b-3 recanalization was achieved more frequently in patients with a favorable outcome (92% of those cases) than in those with a poor outcome (48%; p<0.001). Mean timings of last known normal, symptom onset to femoral artery puncture, and procedure duration were similar between the two groups (table 1). While odds for favorable outcomes showed a trend towards shorter timing of symptom onset, symptom discovery, and CT perfusion to femoral artery puncture, only duration of intervention <30 min was strongly predictive of a favorable outcome (p<0.0001) (table 2).
Discussion
In this multicenter study, we have reported on the clinical outcomes of patients with WUS treated with modern endovascular thrombectomy technologies. The majority of cases presented in our series were treated with stent retriever thrombectomy (88%), and the remaining 12% were treated with primary aspiration alone, using modern large bore aspiration catheters. While experience with the endovascular treatment of WUS has been reported previously, those studies mainly described cases treated with early generation therapies, such as intra-arterial pharmacological thrombolysis, mechanical thrombectomy with the Merci retriever, or intracranial stenting, which limits their relevance to modern clinical practice.5 ,13–15
Another limitation of previously published studies is the lack of a clear distinction between true WUS versus strokes with unwitnessed/unknown times of onset not related to sleep. These studies group and report the outcomes of these two distinct populations of patients together.13 ,16 According to one hypothesis, most WUS occur in the early morning hours, and therefore the time of last known normal becomes less relevant when evaluating such patients for reperfusion strategies.17–19
Nearly half (48%) of the patients in our series achieved a favorable clinical outcome at 90 days, which is higher than the average 28–40% range described in previous studies.5 ,14 ,16 Use of stent retrievers as the primary thrombectomy approach is one possible explanation for such high rates of good outcomes reported in our study. The advantage of stent retriever thrombectomy over early generation devices in achieving higher recanalization rates and improved clinical outcomes was convincingly shown in the TREVO 2 (Trevo versus Merci retrievers for thrombectomy revascularization of large vessel occlusions in acute ischemic stroke) and SWIFT (Solitaire With the Intention for Thrombectomy) trials.6 ,7 However, Stampfl et al recently reported their experience with stent retriever thrombectomy using Solitaire or Revive (Codman Neurovascular, Raynham, Massachusetts, USA) for WUS, and reported only 11% rate of mRS 0–2 at 90 days whereas the rate of symptomatic ICH was 21%. Such an unusually low rate of clinical success with stent retrievers could be explained by limited rates of effective recanalization (only 53% of patients achieved TICI 2b/3 recanalization) and a small sample size (n=19).
Primary aspiration thrombectomy with large bore catheters has not been evaluated in randomized trials but preliminary experience with these catheters also shows their high technical success rate.8 ,20 In our series, 12% of patients were treated with primary aspiration alone. We decided to include patients treated with those devices in our series because such a treatment approach is currently commonly utilized in modern clinical practice.
In all patients included in our series, CTP was used to evaluate the extent of salvageable brain tissue versus ischemic core. Such an imaging selection protocol could be one possible explanation for why outcomes reported in our study were similar between patients who's femoral artery puncture occurred within 8 h from time last known normal versus beyond 8 h. Turk et al11 showed that using CTP based patient selection, comparable clinical outcomes could be achieved in patients treated with intra-arterial therapy within 8 h and those treated >8 h from stroke symptom onset.
However, it is yet to be determined if CT or MR based perfusion is superior to non-contrast CT in evaluating and selecting patients for intra-arterial revascularization. Some studies suggest that advanced modality imaging with CT perfusion or MRI, when compared with non-contrast CT, may result in delays in treatment without reducing hemorrhage rates or improving clinical outcomes.21 Non-contrast CT alone using the Alberta Stroke Program Early CT Score is an alternative strategy for patient selection for intra-arterial therapies that is used by some institutions.21–23
Our study indicates that endovascular treatment of WUS with stent retrievers and aspiration thrombectomy is safe and effective. Although randomized clinical trials are considered the gold standard in evaluating emerging technologies, such as intra-arterial stroke therapies over standard medical therapies, in light of the results of the MR CLEAN (Multi center Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands) trial, which clearly demonstrated the advantage of stent retrievers over medical therapy alone for the treatment of acute stroke, it is uncertain if such randomized trials will be conducted in the future. The DAWN (Trevo and Medical Management Versus Medical Management Alone in Wake Up and Late Presenting Strokes; ClinicalTrials.gov identifier NCT02142283) and POSITIVE (PerfusiOn imaging Selection of Ischemic sTroke PatIents for endoVascular ThErapy; ClinicalTrials.gov identifier NCT01852201) trials are both designed to include patients with WUS. However, with loss of clinical equipoise between the currently existing stroke treatment efficacies and halt of other endovascular trials, such as ESCAPE (Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke) and SWIFT PRIME, the future of WUS trials is unclear.
Conclusion
Our study indicates that endovascular treatment of WUS with stent retrievers and aspiration thrombectomy is safe and effective, and can be safely performed, even in cases when treatment is initiated beyond 8 h of last known normal. Duration of intervention <30 min and its success, defined as TICI 2b-3 recanalization, are strong predictors of favorable clinical outcome at 90 days.
References
Footnotes
Contributors MM, SS, AHS, and EIL are responsible for concepts and design. All authors contributed intellectually. All authors acquired, analyzed, and interpreted the data. The manuscript was prepared by MM and SS. All authors reviewed and made critical revisions to the manuscript.
Competing interests PK: consultant for Stryker Neurovascular, Covidien, and Microvention. EIL: shareholder/ownership interests in Intratech Medical Ltd, Mynx/Access Closure, and Blockade Medical LLC; principal investigator for Covidien US SWIFT PRIME Trials; and other financial support from Abbott for carotid training for physicians. KML: consultant for Stryker. MM: educational grant from Toshiba. AHS: research grants (not related to the present study) from National Institutes of Health (co-investigator: NINDS 1R01NS064592-01A1 and NIBIB 5 RO1 EB002873-07), University at Buffalo (Research Development Award); financial interests in Hotspur, Intratech Medical, StimSox, Valor Medical, Blockade Medical, and Lazarus Effect; consultant for Codman and Shurtleff Inc, Concentric Medical, Covidien Vascular Therapies, GuidePoint Global Consulting, Penumbra, Stryker Neurovascular, and Pulsar Vascular; speakers’ bureaus for Codman and Shurtleff and Genentech; National Steering Committees for Penumbra 3D Separator Trial and Covidien SWIFT PRIME Trial; advisory board for Codman and Shurtleff and Covidien Vascular Therapies; honoraria from Abbott Vascular and Codman and Shurtleff Inc for training other neurointerventionists in carotid stenting and for training physicians in endovascular stenting for aneurysms; consultant/speakers’ bureau/honoraria from Snyder and Toshiba; and speakers’ bureau/honoraria from ev3/Covidien and The Stroke Group. AST: consultant for Stryker, Codman, Penumbra, and Microvention; research grants (not related to present study) from Stryker, Codman, Microvention, Penumbra, and Covidien; financial interests in Medina Medical, Lazarus Effect, Pulsar Vascular, and Blockade Medical. RDT: consultant for Blockade Medical, Covidien, Codman, Microvention, Penumbra, Pulsar Vascular, and Reverse Medical. EV: consultant for Stryker; patent holder—Cordis.
Ethics approval This study was approved by the local institutional review boards at each of the participating centers.
Provenance and peer review Not commissioned; externally peer reviewed.