Infarct in new territory after endovascular stroke treatment: A diffusion-weighted imaging study.

Data on infarcts in new territory (INT) in patients undergoing endovascular stroke treatment for acute large-vessel occlusions are sparse. Aim of this study was to assess the prevalence, risk factors, and clinical relevance of INT. For this purpose, all patients in a single-center prospective registry who underwent endovascular stroke treatment and received pre- and post-interventional diffusion-weighted imaging were included (N = 259). Using an established scoring system, INT were classified according to size (I-III, ≤2 mm, >2 mm ≤20 mm, >20 mm) and likelihood of being related to the intervention (A, high likelihood; B, low likelihood). Additionally, a new type of infarct, that occurred in a territory distal to the occlusion, but was initially not hypoperfused, was defined as an infarct in initially not hypoperfused territory (IINHT). A total of 180 INT and 38 IINHT were observed in 32.8% (N = 85/259) of patients. In most patients, INT were angiographically occult (90.2%), and 13 patients had INT/IINHT larger than 2 cm (type III). Absence of protection during stent-retrieval and a cardio-embolic stroke origin were associated with higher incidence of INT/IINHT, whereas pretreatment with IV tPA showed no association, even when different bolus timing was considered. INT/IINHT were associated with lower rates of functional independence with increasing size type after adjusting for confounders (adjusted Odds Ratio per size group increase 0.63, 95% confidence interval 0.46-0.86). In conclusion, INT and IINHT are not rare, are associated with poor outcome with increasing size, and they may serve as a surrogate endpoint for safety evaluation of new devices and endovascular techniques. Further research on associated factors is warranted.

Endovascular treatment of tandem occlusions in vertebrobasilar stroke: technical aspects and outcome compared with isolated basilar artery occlusion.

BACKGROUND AND PURPOSE: Acute basilar artery occlusion (BAO) is a devastating disease with a high rate of mortality and morbidity, and early recanalization is crucial to achieve a good prognosis. The best treatment strategy for BAO combined with a proximal stenosis (tandem occlusion) is not yet clear. Our study aimed to evaluate whether and how vertebrobasilar tandem occlusions can be treated effectively and safely compared with isolated BAO. MATERIALS AND METHODS: Fifty-two patients with acute vertebrobasilar occlusive stroke treated with mechanical thrombectomy were identified in a prospective database from March 2010 to September 2016. We retrospectively analysed the clinical, technical, and functional outcomes of the patients. RESULTS: Of the 52 patients, 15 presented with a tandem occlusion, 14 with a single intracranial occlusion due to an underlying stenosis, and 23 with a single embolic BAO. Successful recanalization was achieved in all of the patients with tandem occlusions (modified Thrombolysis in Cranial Infarction 2b/3) and in 35 of 37 patients with a single BAO (with and without stenosis). A favourable outcome was achieved (modified Rankin Scale ≤2) in 8 of the 15 patients with a tandem occlusion compared with 4 of the 14 patients with a single BAO with underlying stenosis and 5 of the 23 patients with isolated embolic BAO (p=0.18). CONCLUSIONS: We suggest that endovascular treatment of vertebrobasilar tandem occlusions is safe and feasible, with a high rate of good outcome.

Stent Retriever Thrombectomy with Mindframe Capture LP in Isolated M2 Occlusions.

BACKGROUND AND PURPOSE: Mechanical thrombectomy is an effective recanalization technique in acute ischemic stroke patients with large vessel occlusions; however, it is unclear to what extent stent retriever thrombectomy may be applicable to occlusions of smaller peripheral cerebral vessels. The outcome of patients with isolated M2 occlusions treated with the Mindframe Capture low profile (LP) stent retriever was reviewed. MATERIAL AND METHODS: A retrospective review of prospectively collected data on all consecutive patients treated for isolated M2 occlusions between June 2013 and December 2017 using the Mindframe Capture LP was performed. Technical aspects of the recanalization procedure, recanalization rate, complication rate, and clinical outcome were analyzed. RESULTS: Mechanical thrombectomy with the Mindframe Capture LP was performed in 38 patients (median age 79 years) with an isolated M2 occlusion. The median National Institutes of Health Stroke Scale (NIHSS) score on admission was 7.5 (interquartile range, IQR 5-12) and successful reperfusion modified Thrombolysis in Cerebral Infarction (mTICI 2b or 3) was achieved in 28 patients (74%). A compensated/adjusted modified Rankin Scale (mRS) 0-2 at 3 months was observed in 65% when taking pre-stroke disability into account. Symptomatic intracranial hemorrhage (sICH) occurred in 1 patient (2.6%). Asymptomatic intracranial hemorrhage (aICH) was noted in 8 patients (21%) and a small subarachnoid hemorrhage (SAH) in the immediate vicinity of the target vessel was apparent in 8 patients (21%). CONCLUSION: The Mindframe Capture LP is a technically effective thrombectomy device for the treatment of isolated M2 occlusions. The lower profile of the device is advantageous when targeting peripheral intracranial occlusions.

Safety and Efficacy of Intra-arterial Urokinase After Failed, Unsuccessful, or Incomplete Mechanical Thrombectomy in Anterior Circulation Large-Vessel Occlusion Stroke.

Importance: Achieving complete reperfusion is a key determinant of good outcome in patients treated with mechanical thrombectomy (MT). However, data on treatments geared toward improving reperfusion after incomplete MT are sparse. Objective: To determine whether administration of intra-arterial urokinase is safe and improves reperfusion after failed or incomplete MT. Design, Setting, and Participants: This observational cohort study included a consecutive sample of patients treated with second-generation MT from January 1, 2010, through August 4, 2017. Data were collected from the prospective registry of a tertiary care stroke center. Of 1274 patients screened, 69 refused to participate, and 993 met the observational studies inclusion criteria of a large vessel occlusion in the anterior circulation. Data were analyzed from September 1, 2017, through September 20, 2019. Intervention: One hundred patients received intra-arterial urokinase after failed or incomplete MT using manual microcatheter injections. Main Outcomes and Measures: Primary safety outcome was the occurrence of symptomatic intracranial hemorrhage (sICH) according to the Prolyse in Acute Cerebral Thromboembolism II criteria. Secondary end points included 90-day mortality and 90-day functional independence (defined as modified Rankin Scale score of ≤2). Efficacy was evaluated angiographically, applying the Thrombolysis in Cerebral Infarction (TICI) scale. Results: After exclusion of patients with posterior circulation strokes and those treated with intra-arterial thrombolytics only, 993 patients were included in the final analyses (median age, 74.6 [interquartile range, 62.6-82.2] years; 505 [50.9%] women). Additional intra-arterial urokinase was administered in 100 patients (10.1%). The most common reason for administering intra-arterial urokinase was incomplete reperfusion (TICI<3) after MT (53 [53.0%]). After adjusting for baseline characteristics underlying case selection, intra-arterial urokinase was not associated with an increased risk of sICH (adjusted odds ratio [aOR], 0.81; 95% CI, 0.31-2.13) or 90-day mortality (aOR, 0.78; 95% CI, 0.43-1.40). Among 53 cases of partial or near-complete reperfusion and treated with intra-arterial urokinase, 32 (60.4%) had early reperfusion improvement, and 18 of 53 (34.0%) had an improvement in TICI grade. Correspondingly, patients treated with intra-arterial urokinase had higher rates of functional independence after adjusting for the selection bias favoring a priori poor TICI grades in the intra-arterial urokinase group (aOR, 1.93; 95% CI, 1.11-3.37). Conclusions and Relevance: In selected patients, adjunctive treatment with intra-arterial urokinase during or after MT was safe and improved angiographic reperfusion. Systemic evaluation of this approach in a multicenter prospective registry or a randomized clinical trial seems warranted.

Stent-Retriever Thrombectomy and Rescue Treatment of M1 Occlusions Due to Underlying Intracranial Atherosclerotic Stenosis: Cohort Analysis and Review of the Literature.

BACKGROUND AND PURPOSE: Data on the management of large vessel occlusion in patients with anterior circulation acute ischemic stroke (AIS) due to underlying intracranial stenosis are scarce. The aim of this retrospective study was to compare endovascular treatment and outcome in AIS patients with and without underlying stenosis of the M1 segment. MATERIALS AND METHODS: A total of 533 acute stroke patients with an isolated M1 occlusion who underwent mechanical thrombectomy between 02/2010 and 08/2017 were included. Underlying intracranial atherosclerotic stenosis (ICAS) was present in 10 patients (1.9%), whereas 523 patients (98.1%) had an embolic occlusion without stenosis. RESULTS: There was no difference in age, admission National Institutes of Health Stroke Scale, risk factors, Alberta stroke program early CT score or collaterals between the groups. Procedure time (155 vs 40 min, P = 0.001) was significantly longer in the ICAS group where rescue stent-angioplasty was performed in all patients. There was no statistical difference in final modified thrombolysis in cerebral infarction score between both groups (70 vs 88%, P = 0.115). Favorable outcome (modified Rankin Scale ≤ 2) at 90 days was less frequent in patients with ICAS than in the embolic group (0 vs 49.4%, P = 0.004). The mortality rate tended to be higher in the ICAS group (44.4 vs 19.4%, P = 0.082). CONCLUSION: In patients with AIS, rescue therapy with stent placement to treat underlying ICAS of the M1 segment is technically feasible; however, in our study, a significantly lower rate of favorable outcome was observed in these patients compared to those with thromboembolic M1 occlusions. LEVEL OF EVIDENCE: Level 3, non-randomized controlled study.

Predictors of Unexpected Early Reocclusion After Successful Mechanical Thrombectomy in Acute Ischemic Stroke Patients.

Background and Purpose- Sustained successful reperfusion is an important prognostic factor for good clinical outcome in acute ischemic stroke. We aimed to identify the prevalence, clinical impact, and predictors of early reocclusion after initially successful thrombectomies within a prospective cohort. Methods- A total of 711 stroke patients with successful reperfusion (modified Thrombolysis in Cerebral Infarction, 2b/3) followed with magnetic resonance or computed tomographic angiography at 24 to 48 hours were included. Multivariable logistic regression analysis was used to evaluate associated factors and clinical impact. Results are displayed as adjusted odds ratio (aOR) and 95% CI. Improvement in accuracy of additional imaging findings on angiography control runs after the intervention was evaluated by area under the curve. Results- Early reocclusion was observed in 16 of 711 successfully reperfused patients (2.3%; 95% CI, 1.1-3.3; median delay: 20 hours). Suggestive predictors were higher platelets on admission (aOR, 1.01; 95% CI, 1.01-1.02), prestroke functional dependence (aOR, 7.12; 95% CI, 1.49-34.03), and stroke of undetermined or other specified pathogenesis in the TOAST classification (aOR, 7.19; 95% CI, 1.10-47.05 and aOR, 36.50; 95% CI, 4.47-298.11, respectively). When implementing residual embolic fragments or stenosis at the thrombectomy site into the logistic regression model, discrimination between patients with and without reocclusion improved significantly (area under the curve, 0.955 versus 0.854; P=0.023). Early reocclusion was an independent predictor of unfavorable outcome at 90 days (aOR for modified Rankin Scale ≤2, 0.13; 95% CI, 0.03-0.57). Conclusions- Early reocclusion within 48 hours after successful mechanical thrombectomy is rare but associated with poor outcome. Patients with high platelets on admission and residual embolic fragments or stenosis at the thrombectomy site are at high risk for reocclusion, which may be prevented or corrected after carefully re-evaluating the last angiographic run.

Association of anemia and hemoglobin decrease during acute stroke treatment with infarct growth and clinical outcome.

BACKGROUND AND PURPOSE: Anemia is associated with worse outcome in stroke, but the impact of anemia with intravenous thrombolysis or endovascular therapy has hardly been delineated. The aim of this study was to analyze the role of anemia on infarct evolution and outcome after acute stroke treatment. METHODS: 1158 patients from Bern and 321 from Los Angeles were included. Baseline data and 3 months outcome assessed with the modified Rankin Scale were recorded prospectively. Baseline DWI lesion volumes were measured in 345 patients and both baseline and final infarct volumes in 180 patients using CT or MRI. Multivariable and linear regression analysis were used to determine predictors of outcome and infarct growth. RESULTS: 712 patients underwent endovascular treatment and 446 intravenous thrombolysis. Lower hemoglobin at baseline, at 24h, and nadir until day 5 predicted poor outcome (OR 1.150-1.279) and higher mortality (OR 1.131-1.237) independently of treatment. Decrease of hemoglobin after hospital arrival, mainly induced by hemodilution, predicted poor outcome and had a linear association with final infarct volumes and the amount and velocity of infarct growth. Infarcts of patients with newly observed anemia were twice as large as infarcts with normal hemoglobin levels. CONCLUSION: Anemia at hospital admission and any hemoglobin decrease during acute stroke treatment affect outcome negatively, probably by enlarging and accelerating infarct growth. Our results indicate that hemodilution has an adverse effect on penumbral evolution. Whether hemoglobin decrease in acute stroke could be avoided and whether this would improve outcome would need to be studied prospectively.

Rates and Quality of Preinterventional Reperfusion in Patients With Direct Access to Endovascular Treatment.

Background and Purpose- Preinterventional reperfusion before endovascular treatment (ET) is a benefit of bridging with intravenous tPA (tissue-type plasminogen activator). However, detailed data on reperfusion quality and rates of obviating ET in a cohort of patients with immediate access to ET is lacking. Purpose of this analysis was to evaluate prevalence and quality of preinterventional reperfusion in mothership patients. Methods- All mothership patients (n=627) from a prospective registry subjected to angiography with an intention to perform ET were reviewed. Preinterventional change of occlusion site (COS) was categorized into COS with Thrombolysis in Cerebral Infarction (TICI) 0/1, COS with TICI ≥2a, COS with TICI ≥2b, and COS with perfusion worsening. Predictors and clinical relevance were evaluated using multivariable logistic regression and results are displayed as adjusted odds ratios (aOR) and corresponding 95% confidence intervals (95% CI). Results- Prevalence of COS in all patients was 10.7% (95% CI, 8.3%-13.1%), subdividing into 2.7% COS with TICI 0/1, 6.2% COS with ≥TICI 2a (including 2.9% with TICI ≥2b), and 1.8% COS with perfusion worsening. Factors related to COS with ≥TICI 2a were intravenous tPA (aOR, 11.98; 95% CI, 4.5-31.6), cardiogenic thrombus origin (aOR, 2.3; 95% CI, 1.1-4.6), and thrombus length (aOR per 1 mm increase 0.926; 95% CI, 0.87-0.99). Additional ET was performed despite COS with ≥TICI 2a in 51.3%. COS with ≥TICI 2a showed a tendency for favorable outcomes (modified Rankin Scale, ≤2; aOR, 2.65; 95% CI, 0.98-7.17). Rates of COS with ≥TICI 2a were particularly low in internal carotid artery and proximal M1 occlusions (2.2%; 95% CI, 0.9%-5%), where intravenous tPA was associated with perfusion worsening (aOR, 4.33; 95% CI, 1.12-16.80). Conclusions- Prevalence of preinterventional reperfusion is non-negligible in patients with direct access to ET and is clearly favored by intravenous tPA treatment. However, it is often incomplete and often requires additional ET. Preinterventional reperfusion of internal carotid artery and proximal M1 occlusions is rare and usually of low quality, where intravenous tPA may also promote perfusion worsening.

Multivessel Occlusion in Patients Subjected to Thrombectomy: Prevalence, Associated Factors, and Clinical Implications.

BACKGROUND AND PURPOSE: Patients with embolic large-vessel occlusion may present with additional coincidental acute occlusions within or distant from the involved territory, referred to as multivessel occlusion (MVO). Purpose of this study was to assess prevalence of MVO, associated factors, and clinical relevance in patients undergoing endovascular stroke treatment. METHODS: Image data of consecutive endovascular candidates (n=720) with direct access to angiography were extracted from a prospective registry. Prevalence of MVO was assessed with multimodal magnetic resonance imaging/computed tomography and confirmed by intra-arterial angiography. Explorative analysis of associated factors and clinical relevance was evaluated using multivariable logistic regression including variables with P<0.15 in univariate comparison. Good functional outcome was defined as modified Rankin Scale score ≤2 at day 90. RESULTS: MVO was present in 10.7% of patients (95% confidence interval [CI], 6.4%-13.0%). Two, 3, and 4 concomitant occlusions were found in 80.5%, 16.9%, and 2.6% of MVO cases, respectively. Detection rate on initial radiological report was 54.5%. Downstream MVO was present in around one third of MVO (n=27/77, 35.1%), whereas all other MVO (n=50/77, 64.9%) occurred in different territories. Independent factors related to MVO were statin treatment (adjusted odds ratio [aOR], 0.477; 95% CI, 0.276-0.827), higher systolic blood pressure (aOR per mm Hg increase, 1.014; 95% CI, 1.005-1.023), and primary occlusion site M2 (aOR, 1.870; 95% CI, 1.103-3.170). MVO was related to lower rates of successful reperfusion (aOR, 0.549; 95% CI, 0.316-0.953) and lower rates of good functional outcome (aOR, 0.437; 95% CI, 0.207-0.923). CONCLUSIONS: Every tenth patient subjected to angiography for endovascular stroke treatment experienced MVO in our series, and only half were prospectively identified on preinterventional diagnostic imaging. Patients with MVO had higher baseline systolic blood pressure and were less often medicated with statins, an observation that warrants external validation and evaluation regarding causality. Occurrence of MVO has implication for treatment decisions, negatively affects endovascular treatment success, and is predictive of worse clinical outcome.

Impact of smoking on stroke outcome after endovascular treatment.

BACKGROUND: Recent studies suggest a paradoxical association between smoking status and clinical outcome after intravenous thrombolysis (IVT). Little is known about relationship between smoking and stroke outcome after endovascular treatment (EVT). METHODS: We analyzed data of all stroke patients treated with EVT at the tertiary stroke centre of Berne between January 2005 and December 2015. Using uni- and multivariate modeling, we assessed whether smoking was independently associated with excellent clinical outcome (modified Rankin Scale (mRS) 0-1) and mortality at 3 months. In addition, we also measured the occurrence of symptomatic intracranial hemorrhage (sICH) and recanalization. RESULTS: Of 935 patients, 204 (21.8%) were smokers. They were younger (60.5 vs. 70.1 years of age, p<0.001), more often male (60.8% vs. 52.5%, p = 0.036), had less often from hypertension (56.4% vs. 69.6%, p<0.001) and were less often treated with antithrombotics (35.3% vs. 47.7%, p = 0.004) as compared to nonsmokers. In univariate analyses, smokers had higher rates of excellent clinical outcome (39.1% vs. 23.1%, p<0.001) and arterial recanalization (85.6% vs. 79.4%, p = 0.048), whereas mortality was lower (15.6% vs. 25%, p = 0.006) and frequency of sICH similar (4.4% vs. 4.1%, p = 0.86). After correcting for confounders, smoking still independently predicted excellent clinical outcome (OR 1.758, 95% CI 1.206-2.562; p<0.001). CONCLUSION: Smoking in stroke patients may be a predictor of excellent clinical outcome after EVT. However, these data must not be misinterpreted as beneficial effect of smoking due to the observational study design. In view of deleterious effects of cigarette smoking on cardiovascular health, cessation of smoking should still be strongly recommended for stroke prevention.

Systematic review and meta-analysis on outcome differences among patients with TICI2b versus TICI3 reperfusions: success revisited.

OBJECTIVE: A reperfusion quality of thrombolysis in cerebral infarction (TICI)≥2b has been set as the therapeutic angiography target for interventions in patients with acute ischaemic stroke. This study addresses whether the distinction between TICI2b and TICI3 reperfusions shows a clinically relevant difference on functional outcome. METHODS: A systematic literature review and meta-analysis was carried out and presented in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria to test the primary hypothesis that TICI2b and TICI3 reperfusions are associated with different rates of modified Rankin Scale (mRS) ≤2 at day 90. Secondary endpoints included rates of haemorrhagic transformations, mortality and excellent functional outcome (mRS ≤1). Summary estimates of ORs (sOR) with 95% CI were calculated using the inverse variance heterogeneity model accounting for multiple true effect sizes. RESULTS: Fourteen studies on 2379 successfully reperfused patients were included (1131 TICI3, 1248 TICI2b). TICI3 reperfusions were associated with higher rates of functional independence (1.74, 95% CI 1.44 to 2.10) and excellent functional outcomes (2.01, 95% CI 1.60 to 2.53), also after including adjusted estimates. The safety profile of patients with TICI3 was superior, as demonstrated by lower rates of mortality (sOR 0.59, 95% CI 0.37 to 0.92) and symptomatic intracranial haemorrhages (sOR 0.42, 95% CI 0.25 to 0.71). CONCLUSION: TICI3 reperfusions are associated with superior outcome and better safety profiles than TICI2b reperfusions. This effect seems to be independent of time and collaterals. As reperfusion quality is the most important modifiable predictor of patients' outcome, a more conservative definition of successful therapy and further evaluation of treatment approaches geared towards achieving TICI3 reperfusions are desirable.

Safety of the Solitaire 4 × 40 mm Stent Retriever in the Treatment of Ischemic Stroke.

PURPOSE: Stent retrievers apply mechanical force to the intracranial vasculature. Our aim was to evaluate the safety and efficacy of the long Solitaire 4 × 40 mm stent retriever for large vessel occlusion in stroke patients. METHODS: We conducted a retrospective analysis of all patients treated for acute ischemic large vessel occlusion stroke with the Solitaire 2 FR 4 × 40 device between May and October 2016 at our institution. Patient-specific data at baseline and at discharge were documented. Reperfusion was graded with the thrombolysis in cerebral infarction (TICI) classification. Postinterventional angiograms and follow-up cross-sectional imaging were used to evaluate complications. RESULTS: TICI 2b/3 recanalization was achieved in 20 of 23 patients (87.0%), in 17 patients with the first retriever pass. NIHSS improved from a mean score at presentation of 16 (range 4-36) to 11 (range 0-41) at discharge. Mean mRS score at discharge was 3 (range 0-6) and 3 (range 0-6) at 90 days post-treatment. No infarcts in other territories were observed. One patient showed a (reversible) vasospasm in the postinterventional angiogram and another a small contrast extravasation in follow-up imaging. CONCLUSION: The Solitaire 2 FR 4 × 40 stent retriever is a safe and efficient device for large vessel occlusion acute ischemic stroke with a high recanalization rate and a low peri- and postinterventional complication rate together with a good clinical outcome. Despite potentially higher friction and shearing forces, no increased incidence of visible damage to the vessel wall was observed.

Direct Mechanical Intervention Versus Bridging Therapy in Stroke Patients Eligible for Intravenous Thrombolysis: A Pooled Analysis of 2 Registries.

BACKGROUND AND PURPOSE: Randomized controlled trials have shown that mechanical thrombectomy (MT) plus best medical treatment improves outcome in stroke patients with large-vessel occlusion in the anterior circulation. Whether direct MT is equally effective as bridging thrombolysis (intravenous thrombolysis plus MT) in intravenous thrombolysis eligible patients remains unclear. METHODS: We compared clinical and radiological outcomes at 3 months in 249 bridging patients with 111 patients receiving direct MT for large-vessel occlusion anterior circulation stroke from 2 prospective registries (study period Essen: June 2012 to August 2013, Bern February 2009 to August 2014). We matched all patients from the direct MT group who would have qualified for intravenous thrombolysis with controls from the bridging group, using multivariate and propensity score methods. Subgroup analyses for internal carotid artery occlusions were performed. RESULTS: Baseline characteristics did not differ between the direct MT group and bridging cohort, except for higher rates of coronary heart disease (P=0.029) and shorter intervals from onset to endovascular therapy (P<0.001) in the MT group. Functional outcome, mortality, and intracerebral hemorrhage did not differ, neither in univariate nor after multivariate and propensity score matching. However, in patients with internal carotid artery occlusion, mortality in the direct cohort was significantly lower. CONCLUSIONS: In this matched-pair analysis, there was no difference in outcome in patients with large-vessel occlusion anterior circulation stroke treated with direct MT compared with those treated with bridging thrombolysis; however, mortality in patients with internal carotid artery occlusion treated with direct MT was significantly lower than after bridging thrombolysis. Randomized trials comparing direct MT with bridging therapy are needed.