Impact of Strategy on Clinical Outcome in Large Vessel Occlusion Stroke Successfully Reperfused: ETIS Registry Results.

BACKGROUND AND PURPOSE: Approximately half of the patients with acute ischemic stroke due to anterior circulation large vessel occlusion do not achieve functional independence despite successful reperfusion. We aimed to determine influence of reperfusion strategy (bridging therapy, intravenous thrombolysis alone, or mechanical thrombectomy alone) on clinical outcomes in this population. METHODS: From ongoing, prospective, multicenter, observational Endovascular Treatment in Ischemic Stroke registry in France, all patients with anterior circulation large vessel occlusion who achieved successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b-3) following reperfusion therapy were included. Primary end point was favorable outcome, defined as 90-day modified Rankin Scale score ≤2. Patient groups were compared using those treated with bridging therapy as reference. Differences in baseline characteristics were reduced after propensity score-matching, with a maximum absolute standardized difference of 14% for occlusion site. RESULTS: Among 1872 patients included, 970 (51.8%) received bridging therapy, 128 (6.8%) received intravenous thrombolysis alone, and the remaining 774 (41.4%) received MT alone. The rate of favorable outcome was comparable between groups. Excellent outcome (90-day modified Rankin Scale score 0-1) was achieved more frequently in the bridging therapy group compared with the MT alone (odds ratio after propensity score-matching, 0.70 [95% CI, 0.50-0.96]). Regarding safety outcomes, hemorrhagic complications were similar between the groups, but 90-day mortality was significantly higher in the MT alone group compared with the bridging therapy group (odds ratio, 1.60 [95% CI, 1.09-2.37]). CONCLUSIONS: This real-world observational study of patients with anterior circulation large vessel occlusion demonstrated a similar rate of favorable outcome following successful reperfusion with different therapeutic strategies. However, our results suggest that bridging therapy compared with MT alone is significantly associated with excellent clinical outcome and lower mortality. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03776877.

Does Src Kinase Mediated Vasoconstriction Impair Penumbral Reperfusion?

Despite successful recanalization, a significant number of patients with ischemic stroke experience impaired local brain tissue reperfusion with adverse clinical outcome. The cause and mechanism of this multifactorial complication are yet to be understood. At the current moment, major attention is given to dysfunction in blood-brain barrier and capillary blood flow but contribution of exaggerated constriction of cerebral arterioles has also been suggested. In the brain, arterioles significantly contribute to vascular resistance and thus control of perfusion. Accordingly, pathological changes in arteriolar wall function can, therefore, limit sufficient reperfusion in ischemic stroke, but this has not yet received sufficient attention. Although an increased vascular tone after reperfusion has been demonstrated in several studies, the mechanism behind it remains to be characterized. Importantly, the majority of conventional mechanisms controlling vascular contraction failed to explain elevated cerebrovascular tone after reperfusion. We propose here that the Na,K-ATPase-dependent Src kinase activation are the key mechanisms responsible for elevation of cerebrovascular tone after reperfusion. The Na,K-ATPase, which is essential to control intracellular ion homeostasis, also executes numerous signaling functions. Under hypoxic conditions, the Na,K-ATPase is endocytosed from the membrane of vascular smooth muscle cells. This initiates the Src kinase signaling pathway that sensitizes the contractile machinery to intracellular Ca2+ resulting in hypercontractility of vascular smooth muscle cells and, thus, elevated cerebrovascular tone that can contribute to impaired reperfusion after stroke. This mechanism integrates with cerebral edema that was suggested to underlie impaired reperfusion and is further supported by several studies, which are discussed in this article. However, final demonstration of the molecular mechanism behind Src kinase-associated arteriolar hypercontractility in stroke remains to be done.

What predicts poor outcome after successful thrombectomy in late time windows?

BACKGROUND: Thrombectomy for acute ischemic stroke treatment leads to improved outcomes, but many patients do not achieve a good outcome despite successful reperfusion. We determined predictors of poor outcome after successful thrombectomy (TICI 2b-3) with an emphasis on modifiable factors. METHODS: Patients from the randomized DEFUSE 3 trial who underwent thrombectomy with TICI 2b-3 revascularization were included. Primary outcome was a poor outcome at 90 days (modified Rankin Scale score 3-6). RESULTS: 70 patients were included. Poor outcome patients were older (73.5 vs 66.5 years; P=0.01), more likely to be female (68% vs 39%; P=0.02), had higher NIHSS scores (20 vs 13; P<0.001), and had poor cerebral perfusion collaterals (hypoperfusion intensity ratio) (median 0.45 vs 0.38; P=0.03). Following thrombectomy, poor outcome patients had larger 24 hour' core infarctions (median 59.5 vs 29.9 mL; P=0.01), more core infarction growth (median 33.6 vs 13.4 mL; P<0.001), and more mild (65% vs 50%; P=0.02) and severe (18% vs 0%; P=0.01) reperfusion hemorrhage. In a logistic regression analysis, the presence of any reperfusion hemorrhage (OR 3.3 [95% CI, 1.67 to 5]; P=0.001), age (OR 1.1 [95% CI, 1.03 to 1.11], P=0.004), higher NIHSS (OR 1.25 [95% CI, 1.07 to 1.41], P=0.002), and time from imaging to femoral artery puncture (OR 5 [95% CI, 1.16 to 16.67], P=0.03) independently predicted poor outcomes. CONCLUSIONS: In late time windows, both mild and severe reperfusion hemorrhage were associated with poor outcomes. Older age, higher NIHSS, and increased time from imaging to arterial puncture were also associated with poor outcomes despite successful revascularization. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02586415.

Predictors of poor clinical outcome despite complete reperfusion in acute ischemic stroke patients.

BACKGROUND: In patients suffering from acute ischemic stroke from large vessel occlusion (LVO), mechanical thrombectomy (MT) often leads to successful reperfusion. Only approximately half of these patients have a favorable clinical outcome. Our aim was to determine the prognostic factors associated with poor clinical outcome following complete reperfusion. METHODS: Patients treated with MT for LVO from a prospective single-center stroke registry between July 2015 and April 2019 were screened. Complete reperfusion was defined as Thrombolysis in Cerebral Infarction (TICI) grade 3. A modified Rankin scale at 90 days (mRS90) of 3-6 was defined as 'poor outcome'. A logistic regression analysis was performed with poor outcome as a dependent variable, and baseline clinical data, comorbidities, stroke severity, collateral status, and treatment information as independent variables. RESULTS: 123 patients with complete reperfusion (TICI 3) were included in this study. Poor clinical outcome was observed in 67 (54.5%) of these patients. Multivariable logistic regression analysis identified greater age (adjusted OR 1.10, 95% CI 1.04 to 1.17; p=0.001), higher admission National Institutes of Health Stroke Scale (NIHSS) (OR 1.14, 95% CI 1.02 to 1.28; p=0.024), and lower Alberta Stroke Program Early CT Score (ASPECTS) (OR 0.6, 95% CI 0.4 to 0.84; p=0.007) as independent predictors of poor outcome. Poor outcome was independent of collateral score. CONCLUSION: Poor clinical outcome is observed in a large proportion of acute ischemic stroke patients treated with MT, despite complete reperfusion. In this study, futile recanalization was shown to occur independently of collateral status, but was associated with increasing age and stroke severity.

Leukoaraiosis and acute ischemic stroke: 90-day clinical outcome following endovascular recanalization, with proposed "L-ASPECTS".

BACKGROUND: To assess if leukoaraiosis severity is associated with outcome in patients with acute ischemic stroke (AIS) following endovascular thrombectomy, and to propose a leukoaraiosis-related modification to the ASPECTS score. METHODS: A retrospective review was completed of AIS patients that underwent mechanical thrombectomy for anterior circulation large vessel occlusion. The primary outcome measure was 90-day mRS. A proposed Leukoaraiosis-ASPECTS ("L-ASPECTS") was calculated by subtracting from the traditional ASPECT based on leukoaraiosis severity (1 point subtracted if mild, 2 if moderate, 3 if severe). L-ASEPCTS score performance was validated using a consecutive cohort of 75 AIS LVO patients. RESULTS: 174 patients were included in this retrospective analysis: average age: 68.0±9.1. 28 (16.1%) had no leukoaraiosis, 66 (37.9%) had mild, 62 (35.6%) had moderate, and 18 (10.3%) had severe. Leukoaraiosis severity was associated with worse 90-day mRS among all patients (P=0.0005). Both L-ASPECTS and ASPECTS were associated with poor outcomes, but the area under the curve (AUC) was higher with L-ASPECTS (P<0.0001 and AUC=0.7 for L-ASPECTS; P=0.04 and AUC=0.59 for ASPECTS). In the validation cohort, the AUC for L-ASPECTS was 0.79 while the AUC for ASPECTS was 0.70. Of patients that had successful reperfusion (mTICI 2b/3), the AUC for traditional ASPECTS in predicting good functional outcome was 0.80: AUC for L-ASPECTS was 0.89. CONCLUSIONS: Leukoaraiosis severity on pre-mechanical thrombectomy NCCT is associated with worse 90-day outcome in patients with AIS following endovascular recanalization, and is an independent risk factor for worse outcomes. A proposed L-ASPECTS score had stronger association with outcome than the traditional ASPECTS score.

Filling the gaps on stroke research: Focus on inflammation and immunity.

For the last two decades, researchers have placed hopes in a new era in which a combination of reperfusion and neuroprotection would revolutionize the treatment of stroke. Nevertheless, despite the thousands of papers available in the literature showing positive results in preclinical stroke models, randomized clinical trials have failed to show efficacy. It seems clear now that the existing data obtained in preclinical research have depicted an incomplete picture of stroke pathophysiology. In order to ameliorate bench-to-bed translation, in this review we first describe the main actors on stroke inflammatory and immune responses based on the available preclinical data, highlighting the fact that the link between leukocyte infiltration, lesion volume and neurological outcome remains unclear. We then describe what is known on neuroinflammation and immune responses in stroke patients, and summarize the results of the clinical trials on immunomodulatory drugs. In order to understand the gap between clinical trials and preclinical results on stroke, we discuss in detail the experimental results that served as the basis for the summarized clinical trials on immunomodulatory drugs, focusing on (i) experimental stroke models, (ii) the timing and selection of outcome measuring, (iii) alternative entry routes for leukocytes into the ischemic region, and (iv) factors affecting stroke outcome such as gender differences, ageing, comorbidities like hypertension and diabetes, obesity, tobacco, alcohol consumption and previous infections like Covid-19. We can do better for stroke treatment, especially when targeting inflammation following stroke. We need to re-think the design of stroke experimental setups, notably by (i) using clinically relevant models of stroke, (ii) including both radiological and neurological outcomes, (iii) performing long-term follow-up studies, (iv) conducting large-scale preclinical stroke trials, and (v) including stroke comorbidities in preclinical research.

Mechanical thrombectomy in patients with acute cancer-related stroke: is the stent retriever alone effective?

BACKGROUND: The optimal first-line mechanical thrombectomy (MT) method in cancer-related stroke (CRS) patients with emergent large vessel occlusion (ELVO) remains largely unknown. The aim of this study is to evaluate the efficacy and safety between contact aspiration (CA) first-line thrombectomy and stent retriever (SR) first-line thrombectomy in CRS patients. METHODS: Sixty-two CRS patients with ELVO, who underwent MT between January 2013 and October 2019 at our institution, were retrospectively analyzed. Patients were divided into two groups based on the first-line MT method and compared: the CA group (n=28), which included those who received CA alone or combined CA with SR, and the SR group (n=34), which included those who received conventional SR alone. RESULTS: Overall, reperfusion was successful in 75.8% (47/62) of CRS patients, and a good clinical outcome at 90 days was observed in 17.7%. The CA group showed a higher rate of successful reperfusion (89.3% vs 64.7%, P=0.025) shorter procedure time (22 vs 42 min; P=0.029), higher rate of first pass effect (35.7% vs 11.8%, P=0.025), and lower number of passes (1 vs 3, P=0.023) when compared with the SR group. The procedural and hemorrhagic complication rates were similar between the CA and SR groups. The first-line contact aspiration (OR 11.624, 95% CI 1.041 to 129.752; P=0.046) was an independent predictor of successful reperfusion. CONCLUSIONS: Among patients with CRS, CA - whether alone or in combination with SR - as first-line MT seems to provide more rapid and successful reperfusion when compared with SR.

Follow-up neutrophil-lymphocyte ratio after stroke thrombectomy is an independent biomarker of clinical outcome.

BACKGROUND: Admission neutrophil-lymphocyte ratio (NLR) is significantly correlated to clinical outcomes in acute ischemic stroke (AIS). We investigated follow-up NLR and temporal changes in NLR after endovascular thrombectomy (EVT) with respect to successful revascularization, clinical outcomes, symptomatic intracranial hemorrhage (sICH) and mortality. METHODS: Retrospective analysis of EVT for anterior circulation emergent LVO was performed with both admission (NLR1) and 3-7 day follow-up NLR (NLR2) laboratory data. Patient demographics, National Institutes of Health Stroke Scale (NIHSS) presentations, reperfusion efficacy (modified Thrombolysis in Cerebral Infarction (mTICI) score), sICH, and clinical outcomes (modified Rankin Scale (mRS)) at 90 days were studied. Univariate analyses correlated NLR1, NLR2, and temporal change in NLR (NLR2-NLR1) with successful reperfusion (mTICI ≥2b), favorable outcomes (mRS ≤2), sICH, and mortality. Multivariable logistic regression model evaluated the independent effects of NLR2 on favorable outcomes. RESULTS: 142 AIS patients with median NIHSS 17 underwent EVT within 24 hours, and met NLR laboratory inclusion criteria. Lower follow-up NLR2 and less temporal change in NLR over 3-7 days, but not admission NLR1, inversely correlated with successful reperfusion (p<0.05) and favorable clinical outcomes (p<0.001). Higher follow-up NLR2 and greater temporal change in NLR was significantly associated with sICH and mortality (p≤0.05). In multivariable logistic regression, lower follow-up NLR2 remained a predictor of favorable outcomes (OR 0.785, p=0.001), independent of age or successful reperfusion. CONCLUSIONS: Follow-up NLR is a readily available and modifiable biomarker that correlates with the degree of reperfusion after mechanical stroke thrombectomy. Lower follow-up NLR2 at 3-7 days is associated with successful reperfusion and an independent predictor of favorable clinical outcomes, with reduced risk for sICH and mortality.

Trends in Reperfusion Therapy for In-Hospital Ischemic Stroke in the Endovascular Therapy Era.

Importance: A significant proportion of acute ischemic strokes occur while patients are hospitalized. Limited contemporary data exist on the utilization rates of intravenous thrombolysis or endovascular therapy for in-hospital stroke. Objective: To use a national registry to examine temporal trends in the use of intravenous and endovascular reperfusion therapies for treatment of in-hospital stroke. Design, Setting, and Participants: This retrospective cohort study analyzed data from 267 956 patients who underwent reperfusion therapy for stroke with in-hospital or out-of-hospital onset reported in the Get With the Guidelines-Stroke national registry from January 2008 to September 2018. Exposures: In-hospital onset vs out-of-hospital onset of stroke symptoms. Main Outcomes and Measures: Temporal trends in the use of reperfusion therapy, process measures of quality, and the association between functional outcomes and key patient characteristics, comorbidities, and treatments. Results: Of 67 493 patients with in-hospital stroke onset, this study observed increased rates of vascular risk factors (standardized mean difference >10%) but no significant differences in age or sex in patients undergoing intravenous thrombolysis only (mean [interquartile range {IQR}] age, 72 [80-62] y; 53.2% female) or those undergoing endovascular therapy (mean [IQR] age, 69 [59-79] y; 49.8% female). Of these patients, 10 481 (15.5%) received intravenous thrombolysis and 2494 (3.7%) underwent endovascular therapy. Compared with 2008, in 2018 the proportion of in-hospital stroke among all stroke hospital discharges was higher (3.5% vs 2.7%; P < .001), as was use of intravenous thrombolysis (19.1% vs 9.1%; P < .001) and endovascular therapy (6.4% vs 2.5%; P < .001) in patients with in-hospital stroke, with a significant increase in endovascular therapy in mid-2015 (P < .001). Compared with patients who received intravenous thrombolysis for out-of-hospital stroke onset, those with in-hospital onset were associated with longer median (IQR) times from stroke recognition to cranial imaging (33 [18-60] vs 16 [9-26] minutes; P < .001) and to thrombolysis bolus (81 [52-125] vs 60 [45-84] minutes; P < .001). In adjusted analyses, patients with in-hospital stroke onset who were treated with intravenous thrombolysis were less likely to ambulate independently at discharge (adjusted odds ratio, 0.78; 95% CI, 0.74-0.82; P < .001) and were more likely to die or to be discharged to hospice (adjusted odds ratio, 1.39; 95% CI, 1.29-1.50; P < .001) than patients with out-of-hospital onset who also received intravenous thrombolysis treatment. Comparisons among patients treated with endovascular therapy yielded similar findings. Conclusions and Relevance: In this cohort study, in-hospital stroke onset was increasingly reported and treated with reperfusion therapy. Compared with out-of-hospital stroke onset, in-hospital onset was associated with longer delays to reperfusion and worse functional outcomes, highlighting opportunities to further care for patients with in-hospital stroke onset.

Trends in Endovascular Reperfusion Therapy for Acute Stroke after Introduction of Mechanical Thrombectomy Devices: Japanese Registry of NeuroEndovascular Therapy (JR-NET)3.

In Japan, the era of thrombectomy for acute stroke started when the Merci retriever was approved in 2010 and the Penumbra system in 2011. New-generation Penumbra catheters (MAX series) and stent retrievers were introduced in 2013 and 2014, respectively. The aim of this study was to clarify the general status and trends in endovascular reperfusion therapy for stroke in Japan from 2010 to 2014. We extracted a total of 3705 patients (72.1 ± 12.2 years, 1482 women) from a nationwide study of patients receiving any neuroendovascular treatment, the Japanese Registry of NeuroEndovascular Therapy 3. Reperfusion therapy resulted in a successful reperfusion rate of 59%, and 31% of patients achieved a favorable outcome at 30 days of onset. The frequency of Merci-including procedures increased to 52% in the first half of 2011, but conversely decreased to 1% in the second half of 2014. The frequency of Penumbra-including procedures increased from 18% in the second half of 2011 to 67% in the first half of 2014, decreasing to 38% in the second half of 2014. The reperfusion rate and 30-day clinical outcomes remained almost unchanged until June 2013, and started to improve thereafter, coincident with the introduction and spread of newer-generation devices. The rate of successful reperfusion reached 71-76%, and 36-38% of patients achieved a favorable outcome in 2014. After multivariate adjustment for preprocedure variables, the calendar period from 2013 to 2014 was significantly associated with improvement in reperfusion rates and clinical outcomes.

Onset to reperfusion time as a determinant of outcomes across a wide range of ASPECTS in endovascular thrombectomy: pooled analysis of the SWIFT, SWIFT PRIME, and STAR studies.

BACKGROUND: The time-benefit relationship of endovascular thrombectomy (EVT) according to the size of the core infarct has been incompletely explored in prior studies. We investigated whether established infarct core size on baseline imaging modifies the relationship between onset-to-reperfusion time (OTR) and functional outcomes in patients with acute ischemic stroke treated with EVT. METHODS: We analyzed a database containing individual patient data pooled from three prospective Solitaire stent retriever studies. The inclusion criteria were treatment with a Solitaire device and achievement of substantial reperfusion (modified Thrombolysis in Cerebral Infarction 2b-3). Main analyses were performed in patients with baseline Alberta Stroke Program Early CT Scores (ASPECTSs) of 7-10. RESULTS: Among the 305 patients (mean age 67±13 years, 58% women), the proportions of patients in different categories of pretreatment infarct extent were: small (ASPECTS 9-10) 52.0%, moderate (ASPECTS 7-8) 37.1%, and large (ASPECTS 0-6) 7.6%. The mean OTR was 297±95 min. At 3 months, 60.1% of the patients achieved a good outcome. For OTRs of 2-8 hours, the rates of good outcomes at all time points were higher with higher baseline ASPECTS but declined with similar steepness. Both baseline ASPECTS (OR 1.23 (95% CI 1.04 to 1.45)) and OTR (every 30 min delay, OR 0.80 (95% CI 0.73 to 0.88)) were independently associated with a good 3-month outcome. No interaction between OTR and baseline ASPECTS was observed. CONCLUSIONS: Although patients with higher baseline ASPECTS are more likely to have good clinical outcomes at all OTR intervals after 2 hours, this benefit consistently declines with time, even in patients with a small infarct core, reinforcing the need to treat all patients as quickly as possible.

Effect of time from onset to endovascular therapy on outcomes: the National Acute Stroke Israeli (NASIS)-REVASC registry.

BACKGROUND: Endovascular therapy (EVT) is currently the most effective treatment for emergent large vessel occlusion (ELVO) stroke. Earlier treatment is associated with a better clinical outcome. Our aim was to examine the association between onset-to-EVT (OTE) time and clinical outcomes using real-world nationwide data from the National Acute Stroke ISraeli (NASIS)-REVASC registry. METHODS: Stroke patients undergoing EVT within the Endovascular Capable Centres (ECCs) in Israel between January 2014 and March 2016 were prospectively included. Several clinical and radiological outcomes were evaluated. The association between OTE time and outcomes was analyzed with logistic regression models using time as a continuous variable and then by OTE groups of <2, 2-4, 4-6, and >6 hours. RESULTS: 299 patients with acute stroke were included in the analysis. OTE time was significantly associated with favorable outcomes. ORs for each hour of delay in EVT were 0.84 (95% CI 0.71 to 0.99) for significant early recovery, 0.80 (95% CI 0.68 to 0.94) for discharge to home, 0.80 (95% CI 0.66 to 0.95) for freedom from disability at discharge, and 0.78 (95% CI 0.67 to 0.91) for excellent reperfusion (Thrombolysis in Cerebral Ischemia 3). The <2 OTE group was significantly associated with better outcomes than the ≥2 OTE group including significant early recovery (OR 3.3, 95% CI 1.2 to 9.1), discharge to home (OR 3.32, 95% CI 1.3 to 8.5), and excellent reperfusion (OR 4.6, 95% CI 1.3 to 29.5). The same trend was observed for freedom from disability at discharge and 3 months (OR 2.08, 95% CI 0.7 to 5.7 and OR 2.57, 95% CI 0.8 to 8.3, respectively). Only 1% of transferred patients achieved an OTE time of <2 hours. CONCLUSIONS: Nationwide real-life registry data indicate that benefit from EVT is strongly associated with OTE time and is most prominent within the 'two golden hours' from stroke onset. This time goal may not be applicable in inter-hospital transfer patients.

Incidence of early poststroke seizures during reperfusion therapies in patients with acute ischemic stroke: An observational prospective study: (TESI study: "Trombolisi/Trombectomia e crisi Epilettiche precoci nello Stroke Ischemico").

INTRODUCTION: The aim of this study was to prospectively investigate the occurrence of early poststroke seizures (within 7 days of stroke) in patients undergoing reperfusion therapies (intravenous rtPA [recombinant tissue plasminogen activator] and/or endovascular thrombectomy) in comparison to those not undergoing these procedures. METHODS: Patients aged ≥18 years with acute ischemic stroke admitted in five Italian centers were prospectively recruited. Clinical data, details on stroke type and etiology, stroke treatment, and radiological data were collected. The frequency of early poststroke seizures was assessed, and predictive factors for their occurrence were evaluated. RESULTS: Five hundred and sixteen patients (262 in the reperfusion therapies group) were included. Stroke severity on admission and at discharge was higher among patients undergoing reperfusion therapies. Ten patients (3.8%) undergoing reperfusion therapies and 6 (2.3%) of those not receiving these treatments experienced early poststroke seizures (p = 0.45). There were no differences in any of the baseline characteristics between patients experiencing and those not experiencing early seizures. CONCLUSION: The incidence of early poststroke seizures was overall rare, and no significant differences emerged between patients receiving and those not receiving reperfusion therapies. This article is part of the Special Issue "Seizures and Stroke".

Blood pressure reduction and outcome after endovascular therapy with successful reperfusion: a multicenter study.

BACKGROUND: Elevated systolic blood pressure (SBP) after mechanical thrombectomy (MT) correlates with worse outcome. However, the association between SBP reduction (SBPr) and outcome after successful reperfusion with MT is not well established. OBJECTIVE: To investigate the association between SBPr in the first 24 hours after successful reperfusion and the functional and safety outcomes of MT. METHODS: A multicenter retrospective study, which included 10 comprehensive stroke centers, was carried out. Patients with acute ischemic stroke and anterior circulation large vessel occlusions who achieved successful reperfusion via MT were included. SBPr was calculated using the formula 100×([admission SBP-mean SBP]/admission SBP). Poor outcome was defined as a modified Rankin Scale (mRS) score of 3-6 at 90 days. Safety endpoints included symptomatic intracerebral hemorrhage, mortality, and requirement for hemicraniectomy during admission. A generalized mixed linear model was used to study the association between SBPr and outcomes. RESULTS: A total of 1361 patients were included in the final analysis. SBPr as a continuous variable was inversely associated with poor outcome (OR=0.97; 95% CI 0.95 to 0.98; p<0.001) but not with the safety outcomes. Subanalysis based on reperfusion status showed that SBPr was associated with lower odds of poor outcome only in patients with complete reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI 3)) but not in patients with incomplete reperfusion (mTICI 2b). When SBPr was divided into categories (<1%, 1%-10%, 11%-20%, >20%), the rate of poor outcome was highest in the first group. CONCLUSION: SBPr in the first 24 hours after successful reperfusion was inversely associated with poor outcome. No association between SBPr and safety outcome was found.

Reperfusion therapies and poststroke seizures.

Seizures are not only a frequent complication of stroke but have been associated with an unfavorable functional and vital outcome of patients who have had stroke. Facing a new paradigm of acute standard stroke care, acute symptomatic seizures in this clinical setting deserve to be rethought. Reperfusion therapies, the gold standard treatment for acute ischemic stroke, improve long-term survival and outcome of patients who have had stroke and have been associated both with clinical seizures and the occurrence of epileptiform activity in the electroencephalogram (EEG). This narrative review describes the different physiopathological mechanisms underlying the possible association between reperfusion therapies and seizures, both acute symptomatic seizures and unprovoked seizures, and the current evidence regarding the risk of poststroke seizures in treated patients. It also identifies the gaps in our knowledge to foster future studies in this field. By different mechanisms, reperfusions therapies may have opposing effects on the risk of poststroke seizures. There is a need for a better definition of the specific physiopathology of seizures in clinical practice, as many factors can be recognized. Additionally, most of the current clinical evidence refers to acute symptomatic seizures and not to unprovoked seizures or poststroke epilepsy, and our analysis does not support the existence of a strong association between thrombolysis and poststroke seizures. So far, the impact of reperfusion therapies on the frequency of poststroke seizures is unclear. To study this effect, many clinical challenges must be overcome, including a better and clear operational definition of seizures and stroke characteristics, the standard of stroke and epilepsy care and EEG monitoring, and the degree of reperfusion success. Prospective, high quality, larger, and longer follow-up multicentric studies are urgently needed. Additionally, stroke registries can also prove useful in better elucidate whether there is an association between reperfusion therapies and seizures. This article is part of the Special Issue "Seizures & Stroke".

Exploring Reperfusion Following Endovascular Thrombectomy.

Background and Purpose- Cerebral perfusion in acute ischemic stroke patients is often assessed before endovascular thrombectomy (EVT), but rarely after. Perfusion data obtained following EVT may provide additional prognostic information. We developed a tool to quantitatively derive perfusion measurements from digital subtraction angiography (DSA) data and examined perfusion in patients following EVT. Methods- Source DSA images from acute anterior circulation stroke patients undergoing EVT were retrospectively assessed. Following deconvolution, maps of mean transit time (MTT) were generated from post-EVT DSA source data. Thrombolysis in Cerebral Infarction grades and MTT in patients with and without hemorrhagic transformation (HT) at 24 hours were compared. Receiver operating characteristic modeling was used to classify the presence/absence of HT at 24 hours by MTT. Results- Perfusion maps were generated in 50 patients using DSA acquisitions that were a median (interquartile range) of 9 (8-10) seconds in duration. The median post-EVT MTT within the affected territory was 2.6 (2.2-3.3) seconds. HT was observed on follow-up computed tomography in 16 (32%) patients. Thrombolysis in Cerebral Infarction grades did not differ in patients with HT from those without (P=0.575). Post-EVT MTT maps demonstrated focal areas of hyperperfusion (n=8) or persisting hypoperfusion (n=3) corresponding to the regions where HT later developed. The relationship between MTT and HT was U-shaped; HT occurred in patients at both the lowest and highest extremes of MTT. An MTT threshold <2 or >4 seconds was 81% sensitive and 94% specific for classifying the presence of HT at follow-up. Conclusions- Perfusion measurements can be obtained using DSA perfusion with minimal changes to current stroke protocols. Perfusion imaging post-recanalization may have additional clinical utility beyond visual assessment of source angiographic images alone.

Acute ischaemic stroke: challenges for the intensivist.

PURPOSE: To provide an update about the rapidly developing changes in the critical care management of acute ischaemic stroke patients. METHODS: A narrative review was conducted in five general areas of acute ischaemic stroke management: reperfusion strategies, anesthesia for endovascular thrombectomy, intensive care unit management, intracranial complications, and ethical considerations. RESULTS: The introduction of effective reperfusion strategies, including IV thrombolysis and endovascular thrombectomy, has revolutionized the management of acute ischaemic stroke and transformed outcomes for patients. Acute therapeutic efforts are targeted to restoring blood flow to the ischaemic penumbra before irreversible tissue injury has occurred. To optimize patient outcomes, secondary insults, such as hypotension, hyperthermia, or hyperglycaemia, that can extend the penumbral area must also be prevented or corrected. The ICU management of acute ischaemic stroke patients, therefore, focuses on the optimization of systemic physiological homeostasis, management of intracranial complications, and neurological and haemodynamic monitoring after reperfusion therapies. Meticulous blood pressure management is of central importance in improving outcomes, particularly in patients that have undergone reperfusion therapies. CONCLUSIONS: While consensus guidelines are available to guide clinical decision making after acute ischaemic stroke, there is limited high-quality evidence for many of the recommended interventions. However, a bundle of medical, endovascular, and surgical strategies, when applied in a timely and consistent manner, can improve long-term stroke outcomes.

Mothership versus drip and ship for thrombectomy in patients who had an acute stroke: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of mechanical thrombectomy (MT) in acute ischemic stroke due to large vessel occlusion is time-dependent. While only stroke centers with endovascular capabilities perform MT, many patients who had a stroke initially present to the closest primary stroke centers capable of administering earlier intravenous thrombolysis, and then require to be transferred to a comprehensive stroke center for MT. PURPOSE: To compare the outcomes of this care pathway (drip and ship (DS)) with that whereby patients are directly transferred to a comprehensive stroke center (mothership (MS)). METHODS: We performed a systematic review and meta-analysis of published studies using several electronic databases to determine whether successful reperfusion (modified Thrombolysis In Cerebral Infarction ≥2b), functional independence at 90 days (modified Rankin Scale score ≤2), symptomatic intracranial hemorrhage, and 90-day mortality differed between those who underwent MT with the DS or the MS treatment pathway. Outcomes were meta-analyzed and the results expressed as adjusted relative risk (aRR) for the primary analysis and unadjusted relative risk (uRR) for secondary analysis. RESULTS: Eight studies including 2068 patients were selected, including one study reporting results fully adjusted for baseline characteristics. Patients undergoing MS had better functional independence than those undergoing DS (uRR=0.87, 95% CI 0.81 to 0.93; aRR=0.87, 95% CI 0.77 to 0.98). No difference was found between the treatment pathways in successful reperfusion (uRR=1.05, 95% CI 0.95 to 1.15; aRR=1.00, 95% CI 0.92 to 1.10), symptomatic intracranial hemorrhage (uRR=1.37, 95% CI 0.91 to 2.06; aRR, 1.53, 95% CI 0.79 to 2.98), and 90-day mortality (uRR=1.00, 95% CI 0.84 to 1.19; aRR=1.21, 95% CI 0.89 to 1.64). CONCLUSIONS: Patients who had an acute ischemic stroke admitted directly to a comprehensive stroke center (MS patients) with endovascular capacities may have better 90-day outcomes than those receiving DS treatment. However, major limitations of current evidence (ie, retrospective studies and selection bias) suggest a need for adequately powered studies. Multicenter randomized controlled trials are expected to answer this question.

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.

Admission hyperglycemia and outcomes in large vessel occlusion strokes treated with mechanical thrombectomy.

BACKGROUND AND PURPOSE: Higher admission serum glucose levels have been associated with poor outcomes in patients with acute ischemic stroke (AIS) treated with IV thrombolysis. We sought to evaluate the association of admission serum glucose with early outcomes of patients with emergent large vessel occlusion (ELVO) treated with mechanical thrombectomy (MT). METHODS: Consecutive AIS patients due to ELVO treated with MT in three tertiary stroke centers were evaluated. The following outcomes were documented using standard definitions: symptomatic intracranial hemorrhage (sICH), complete reperfusion, mortality, functional independence (modified Rankin Scale (mRS) score of 0-2), and functional improvement (shift in mRS score) at 3 months. The association of admission serum glucose and admission hyperglycemia (>140 mg/dL) with outcomes was evaluated using univariable and multivariable binary and ordinal logistic regression models. RESULTS: 231 AIS patients with ELVO (mean age 62±14 years, 51% men, median admission National Institute of Health Stroke Scale score 16 points (IQR 12-21), median admission serum glucose 125 mg/dL (IQR 104-162)) were treated with MT. Admission hyperglycemia was associated with a lower likelihood of functional improvement (common OR 0.53; 95% CI 0.31 to 0.97; p=0.027) and higher odds of 3 month mortality (OR 2.76; 95% CI 1.40 to 5.44; p=0.004) in multivariable analyses adjusting for potential confounders. A 10 mg/dL increase in admission blood glucose was associated with a higher likelihood of sICH (OR 1.07; 95% CI 1.01 to 1.13; p=0.033) and 3 month mortality (OR 1.07; 95% CI 1.02 to 1.12; p=0.004) in multivariable models. There was no association between admission serum glucose or hyperglycemia and complete reperfusion. CONCLUSIONS: Higher admission serum glucose and admission hyperglycemia are independent predictors of adverse outcomes in ELVO patients treated with MT.