Effectiveness of Thrombectomy in Stroke According to Baseline Prognostic Factors: Inverse Probability of Treatment Weighting Analysis of a Population-Based Registry

Background and Purpose In real-world practice, the benefit of mechanical thrombectomy (MT) is uncertain in stroke patients with very favorable or poor prognostic profiles at baseline. We studied the effectiveness of MT versus medical treatment stratifying by different baseline prognostic factors. Methods Retrospective analysis of 2,588 patients with an ischemic stroke due to large vessel occlusion nested in the population-based registry of stroke code activations in Catalonia from January 2017 to June 2019. The effect of MT on good functional outcome (modified Rankin Score ≤2) and survival at 3 months was studied using inverse probability of treatment weighting (IPTW) analysis in three pre-defined baseline prognostic groups: poor (if pre-stroke disability, age >85 years, National Institutes of Health Stroke Scale [NIHSS] >25, time from onset >6 hours, Alberta Stroke Program Early CT Score <6, proximal vertebrobasilar occlusion, supratherapeutic international normalized ratio >3), good (if NIHSS <6 or distal occlusion, in the absence of poor prognostic factors), or reference (not meeting other groups’ criteria). Results Patients receiving MT (n=1,996, 77%) were younger, had less pre-stroke disability, and received systemic thrombolysis less frequently. These differences were balanced after the IPTW stratified by prognosis. MT was associated with good functional outcome in the reference (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.0 to 4.4), and especially in the poor baseline prognostic stratum (OR, 3.9; 95% CI, 2.6 to 5.9), but not in the good prognostic stratum. MT was associated with survival only in the poor prognostic stratum (OR, 2.6; 95% CI, 2.0 to 3.3).Conclusions Despite their worse overall outcomes, the impact of thrombectomy over medical management was more substantial in patients with poorer baseline prognostic factors than patients with good prognostic factors.

Impact of Multiphase Computed Tomography Angiography for Endovascular Treatment Decision-Making on Outcomes in Patients with Acute Ischemic Stroke

Background and Purpose Various imaging paradigms are used for endovascular treatment (EVT) decision-making and outcome estimation in acute ischemic stroke (AIS). We aim to compare how these imaging paradigms perform for EVT patient selection and outcome estimation. Methods Prospective multi-center cohort study of patients with AIS symptoms with multi-phase computed tomography angiography (mCTA) and computed tomography perfusion (CTP) baseline imaging. mCTA-based EVT-eligibility was defined as presence of large vessel occlusion (LVO) and moderate-to-good collaterals on mCTA. CTP-based eligibility was defined as presence of LVO, ischemic core (defined on relative cerebral blood flow, absolute cerebral blood flow, and cerebral blood volume maps) <70 mL, mismatch-ratio >1.8, absolute mismatch >15 mL. EVT-eligibility and adjusted rates of good outcome (modified Rankin Scale 0–2) based on these imaging paradigms were compared.Results Of 289/464 patients with LVO, 263 (91%) were EVT-eligible by mCTA-criteria versus 63 (22%), 19 (7%) and 103 (36%) by rCBF, aCBF, and CBV-CTP-criteria. CTP and mCTA-criteria were discordant in 40% to 53%. Estimated outcomes were best in patients who met both mCTA and CTP eligibility-criteria and were treated with EVT (62% to 87% good outcome). Patients eligible for EVT by mCTA-criteria and not by CTP-criteria receiving EVT achieved good outcome rates of 53% to 57%. Few patients met CTP-criteria and not mCTA-criteria for EVT.Conclusions Simpler imaging selection criteria that rely on little else than detection of the occluded blood vessel may be more sensitive and less specific, thus resulting in more patients being offered EVT and arguably benefiting from it.

Thrombolysis Improves Reperfusion and the Clinical Outcome in Tandem Occlusion Stroke Related to Cervical Dissection: TITAN and ETIS Pooled Analysis

Background and Purpose Despite the widespread adoption of mechanical thrombectomy (MT) for the treatment of large vessel occlusion stroke (LVOS) in the anterior circulation, the optimal strategy for the treatment tandem occlusion related to cervical internal carotid artery (ICA) dissection is still debated. This individual patient pooled analysis investigated the safety and efficacy of prior intravenous thrombolysis (IVT) in anterior circulation tandem occlusion related to cervical ICA dissection treated with MT.Methods We performed a retrospective analysis of two merged prospective multicenter international real-world observational registries: Endovascular Treatment in Ischemic Stroke (ETIS) and Thrombectomy In TANdem occlusions (TITAN) registries. Data from MT performed in the treatment of tandem LVOS related to cervical ICA dissection between January 2012 and December 2019 at 24 comprehensive stroke centers were analyzed. The primary endpoint was a favorable outcome defined as 90-day modified Rankin Scale (mRS) score of 0–2.Results The study included 144 patients with tandem occlusion LVOS due to cervical ICA dissection, of whom 94 (65.3%) received IVT before MT. Prior IVT was significantly associated with a better clinical outcome considering the mRS shift analysis (common odds ratio, 2.59; 95% confidence interval [CI], 1.35 to 4.93; P=0.004 for a 1-point improvement) and excellent outcome (90-day mRS 0–1) (adjusted odds ratio [aOR], 4.23; 95% CI, 1.60 to 11.18). IVT was also associated with a higher rate of intracranial successful reperfusion (83.0% vs. 64.0%; aOR, 2.70; 95% CI, 1.21 to 6.03) and a lower rate of symptomatic intracranial hemorrhage (4.3% vs. 14.8%; aOR, 0.21; 95% CI, 0.05 to 0.80).Conclusions Prior IVT before MT for the treatment of tandem occlusion related to cervical ICA dissection was safe and associated with an improved 90-day functional outcome.

Post-Stroke Cognitive Impairment: Pathophysiological Insights into Brain Disconnectome from Advanced Neuroimaging Analysis Techniques

The neurological symptoms of stroke have traditionally provided the foundation for functional mapping of the brain. However, there are many unresolved aspects in our understanding of cerebral activity, especially regarding high-level cognitive functions. This review provides a comprehensive look at the pathophysiology of post-stroke cognitive impairment in light of recent findings from advanced imaging techniques. Combining network neuroscience and clinical neurology, our research focuses on how changes in brain networks correlate with post-stroke cognitive prognosis. More specifically, we first discuss the general consequences of stroke lesions due to damage of canonical resting-state large-scale networks or changes in the composition of the entire brain. We also review emerging methods, such as lesion-network mapping and gradient analysis, used to study the aforementioned events caused by stroke lesions. Lastly, we examine other patient vulnerabilities, such as superimposed amyloid pathology and blood-brain barrier leakage, which potentially lead to different outcomes for the brain network compositions even in the presence of similar stroke lesions. This knowledge will allow a better understanding of the pathophysiology of post-stroke cognitive impairment and provide a theoretical basis for the development of new treatments, such as neuromodulation.

Hemodynamics of Leptomeningeal Collaterals after Large Vessel Occlusion and Blood Pressure Management with Endovascular Treatment

Endovascular therapy (EVT) is an effective treatment for ischemic stroke due to large vessel occlusion (LVO). Unlike intravenous thrombolysis, EVT enables visualization of the restoration of blood flow, also known as successful reperfusion in real time. However, until successful reperfusion is achieved, the survival of the ischemic brain is mainly dependent on blood flow from the leptomeningeal collaterals (LMC). It plays a critical role in maintaining tissue perfusion after LVO via pre-existing channels between the arborizing pial small arteries or arterioles overlying the cerebral hemispheres. In the ischemic territory where the physiologic cerebral autoregulation is impaired and the pial arteries are maximally dilated within their capacity, the direction and amount of LMC perfusion rely on the systemic perfusion, which can be estimated by measuring blood pressure (BP). After the EVT procedure, treatment focuses on mitigating the risk of hemorrhagic transformation, potentially via BP reduction. Thus, BP management may be a key component of acute care for patients with LVO stroke. However, the guidelines on BP management during and after EVT are limited, mostly due to the scarcity of high-level evidence on this issue. In this review, we aim to summarize the anatomical and physiological characteristics of LMC to maintain cerebral perfusion after acute LVO, along with a landscape summary of the literature on BP management in endovascular treatment. The objective of this review is to describe the mechanistic association between systemic BP and collateral perfusion after LVO and thus provide clinical and research perspectives on this topic.

Mechanical Thrombectomy in Patients with a Large Ischemic Volume at Presentation: Systematic Review and Meta-Analysis

The benefits of mechanical thrombectomy (MT) for patients with acute ischemic stroke (AIS) and a large ischemic core (LIC) at presentation are uncertain. We aimed to obtain up-to-date aggregate estimates of the outcomes following MT in patients with volumetrically assessed LIC. We conducted a Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-conformed, PROSPERO-registered, systematic review and meta-analysis of studies that included patients with AIS and a baseline LIC treated with MT, reported ischemic core volume quantitatively, and included patients with a LIC defined as a core volume ≥50 mL. The search was restricted to studies published between January 2015 and June 2020. Random-effects-meta-analysis was used to assess the effect of MT on 90-day unfavorable outcome (i.e., modified Rankin Scale [mRS] 3–6), mortality, and symptomatic intracranial hemorrhage (sICH) occurrence. Sensitivity analyses were performed for imaging-modality (computed tomography-perfusion or magnetic resonance-diffusion weighted imaging) and LIC-definition (≥50 or ≥70 mL). We analyzed 10 studies (954 patients), including six (682 patients) with a control group, allowing to compare 332 patients with MT to 350 who received best-medical-management alone. Overall, after MT the rate of patients with mRS 3–6 at 90 days was 74% (99% confidence interval [CI], 67 to 84; Z-value=7.04; I2=92.3%) and the rate of 90-day mortality was 36% (99% CI, 33 to 40; Z-value=–7.07; I2=74.5). Receiving MT was associated with a significant decrease in mRS 3–6 odds ratio (OR) 0.19 (99% CI, 0.11 to 0.33; P<0.01; Z-value=–5.92; I2=62.56) and in mortality OR 0.60 (99% CI, 0.34 to 1.06; P=0.02; Z-value=–2.30; I2=58.72). Treatment group did not influence the proportion of patients experiencing sICH, OR 0.96 (99% CI, 0.2 to 1.49; P=0.54; Z-value=–0.63; I2=64.74). Neither imaging modality for core assessment, nor LIC definition influenced the aggregated outcomes. Using aggregate estimates, MT appeared to decrease the risk of unfavorable functional outcome in patients with a LIC assessed volumetrically at baseline.

Stroke Etiology and Outcomes after Endovascular Thrombectomy: Results from the SITS Registry and a Meta-Analysis

Background and Purpose The influence of stroke etiology on outcomes after endovascular thrombectomy (EVT) is not well understood. We aimed to investigate whether stroke etiology subgrouped as large artery atherosclerosis (LAA) and cardiac embolism (CE) influences outcomes in large artery occlusion (LAO) treated by EVT.Methods We included EVT treated LAO stroke patients registered in the Safe Implementation of Treatment in Stroke (SITS) thrombectomy register between January 1, 2014 and September 3, 2019. Primary outcome was successful reperfusion (modified Treatment in Cerebral Infarction 2b-3). Secondary outcomes were symptomatic intracranial hemorrhage (SICH), 3-month functional independence (modified Ranking Scale 0–2) and death. Multivariable logistic regression models were used for comparisons. In addition, a meta-analysis of aggregate data from the current literature was conducted (PROSPERO, ID 167447).Results Of 7,543 patients, 1,903 (25.2%) had LAA, 3,214 (42.6%) CE, and 2,426 (32.2%) unknown, other, or multiple etiologies. LAA patients were younger (66 vs. 74, P<0.001) and had lower National Institutes of Health Stroke Scale score at baseline (15 vs. 16, P<0.001) than CE patients. Multivariable analyses showed that LAA patients had lower odds of successful reperfusion (odds ratio [OR], 0.70; 95% confidence interval [CI], 0.57 to 0.86) and functional independence (OR, 0.74; 95% CI, 0.63 to 0.85), higher risk of death (OR, 1.44; 95% CI, 1.21 to 1.71), but no difference in SICH (OR, 1.09; 95% CI, 0.71 to 1.66) compared to CE patients. The systematic review found 25 studies matching the criteria. The meta-analysis did not find any difference between etiologies. Conclusions From the SITS thrombectomy register, we observed a lower chance of reperfusion and worse outcomes after thrombectomy in patients with LAA compared to CE etiology, despite more favorable baseline characteristics. In contrast, the meta-analysis did not find any difference between etiologies with aggregate data.