Systemic biomarker associated with poor outcome after futile reperfusion.

BACKGROUND: Successful recanalization does not lead to complete tissue reperfusion in a considerable percentage of ischemic stroke patients. This study aimed to identify biomarkers associated with futile recanalization. Leukoaraiosis predicts poor outcomes of this phenomenon. Soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK), which is associated with leukoaraiosis degrees, could be a potential biomarker. METHODS: This study includes two cohorts of ischemic stroke patients in a multicentre retrospective observational study. Effective reperfusion, defined as a reduction of ≥8 points in the National Institutes of Health Stroke Scale (NIHSS) within the first 24 h, was used as a clinical marker of effective reperfusion. RESULTS: In the first cohort study, female sex, age, and high NIHSS at admission (44.7% vs. 81.1%, 71.3 ± 13.7 vs. 81.1 ± 6.7; 16 [13, 21] vs. 23 [17, 28] respectively; p < .0001) were confirmed as predictors of futile recanalization. ROC curve analysis showed that leukocyte levels (sensitivity of 99%, specificity of 55%) and sTWEAK level (sensitivity of 92%, specificity of 88%) can discriminate between poor and good outcomes. Both biomarkers simultaneously are higher associated with outcome after effective reperfusion (OR: 2.17; CI 95% 1.63-4.19; p < .0001) than individually (leukocytes OR: 1.38; CI 95% 1.00-1.64, p = .042; sTWEAK OR: 1.00; C I95% 1.00-1.01, p = .019). These results were validated using a second cohort, where leukocytes and sTWEAK showed a sensitivity of 100% and specificity of 66.7% and 75% respectively. CONCLUSIONS: Leukocyte and sTWEAK could be biomarkers of reperfusion failure and subsequent poor outcomes. Further studies will be necessary to explore its role in reperfusion processes.

General anesthesia versus conscious sedation during endovascular treatment in posterior circulation large vessel occlusion: A systematic review and meta-analysis.

Purpose: The optimal anesthetic approach in the endovascular treatment (EVT) of patients with posterior circulation large vessel occlusion (PC-LVO) strokes is not clear. Little data has been published and no randomized clinical trials have been conducted so far. We aimed to perform an updated meta-analysis to compare clinical and procedural outcomes between conscious sedation (CS) and general anesthesia (GA). Methods: We reviewed the literature of the studies reporting CS and GA in patients with endovascularly-treated PC-LVO. The primary outcome was the functional outcome at 3 months measured using the modified Rankin Scale (mRS). A good functional outcome was defined as having a mRS 0-2. Secondary outcomes were mortality at 3 months, final successful recanalization (modified Thrombolysis in Cerebral Infarction (mTICI) scale from 2b to 3) and complete recanalization (mTICI of 3) and times from stroke onset to EVT completion. Random-effects models were completed to pool the outcomes and the I 2 value was calculated to assess heterogeneity. Findings: Eight studies with a total of 1351 patients were included. The pooled results reveal that CS use was associated with higher rates of good outcome (OR 2.41, 95% CI 1.58-3.64, I 2 = 49.67%) and with lower mortality at 3 months (OR 0.48, 95% CI 0.28-0.82, I 2 =57.11%). No significant differences were observed in the final reperfusion rates, procedural duration, and time from stroke onset to EVT completion. Conclusion: In this meta-analysis, GA was associated with significantly lower rates of functional independence at 3 months in patients with PC-LVO strokes.

Clinical Parameters and Epigenetic Biomarkers of Plaque Vulnerability in Patients with Carotid Stenosis.

Atheromatous disease is the first cause of death and dependency in developed countries and carotid artery atherosclerosis is one of the main causes of severe ischaemic strokes. Current management strategies are mainly based on the degree of stenosis and patient selection has limited accuracy. This information could be complemented by the identification of biomarkers of plaque vulnerability, which would permit patients at greater and lesser risk of stroke to be distinguished, thus enabling a better selection of patients for surgical or intensive medical treatment. Although several circulating protein-based biomarkers with significance for both the diagnosis of carotid artery disease and its prognosis have been identified, at present, none have been clinically implemented. This review focuses especially on the most relevant clinical parameters to take into account in routine clinical practice and summarises the most up-to-date data on epigenetic biomarkers of carotid atherosclerosis and plaque vulnerability.

Progressive Lacunar Strokes: A Predictive Score.

BACKGROUND AND PURPOSE: Progressive lacunar syndromes (PLS) occur in up to 20-30% of patients with lacunar strokes, increasing the risk of long term dependency. Our aim is to develop a predictive score to identify patients at high risk of presenting PLS. METHODS: We derived a risk score for PLS in a cohort of consecutive patients (n=187) presenting with one of the five classic lacunar syndromes (LS) and absence of vascular occlusion, perfusion deficit or symptomatic stenosis. A risk score was developed using the coefficients from the logistic regression model, and receiver operating characteristic (ROC) analysis was conducted to assess the prognostic value of the risk score. Sensitivity, specificity and accuracy were estimated for each total point score. RESULTS: Out of 187 patients included in our sample, 52 (27.8%) presented PLS. Previous history of diabetes mellitus (1 point), diastolic blood pressure at admission (2 points), clinical deficits consistent with a pure motor syndrome (1 point) and asymptomatic intracranial atheromatosis or stenosis in non-symptomatic territory (1 point) were independent predictors for PLS. The estimated area under the ROC curve for this model was 0.77 (95% CI,0.68 - 0.84). CONCLUSION: This score could be a useful tool in routine clinical practice to predict the occurrence of PLS, allowing the identification of those patients with LS who are at high risk of long term dependency due to early neurological worsening, and who would benefit the most from an intensive treatment.

Cav-1 Protein Levels in Serum and Infarcted Brain Correlate with Hemorrhagic Volume in a Mouse Model of Thromboembolic Stroke, Independently of rt-PA Administration.

Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) is currently the only FDA-approved drug for acute ischemic stroke. However, its administration is still limited due to the associated increased risk of hemorrhagic transformation (HT). rt-PA may exacerbate blood-brain barrier (BBB) injury by several mechanisms that have not been fully elucidated. Caveolin-1 (Cav-1), a major structural protein of caveolae, has been linked to the endothelial barrier function. The effects of rt-PA on Cav-1 expression remain largely unknown. Here, Cav-1 protein expression after ischemic conditions, with or without rt-PA administration, was analyzed in a murine thromboembolic middle cerebral artery occlusion (MCAO) and in brain microvascular endothelial bEnd.3 cells subjected to oxygen/glucose deprivation (OGD). Our results show that Cav-1 is overexpressed in endothelial cells of infarcted area and in bEnd.3 cell line after ischemia but there is disagreement regarding rt-PA effects on Cav-1 expression between both experimental models. Delayed rt-PA administration significantly reduced Cav-1 total levels from 24 to 72 h after reoxygenation and increased pCav-1/Cav-1 at 72 h in the bEnd.3 cells while it did not modify Cav-1 immunoreactivity in the infarcted area at 24 h post-MCAO. Importantly, tissue Cav-1 positively correlated with Cav-1 serum levels at 24 h post-MCAO and negatively correlated with the volume of hemorrhage after infarction, the latter supporting a protective role of Cav-1 in cerebral ischemia. In addition, the negative association between baseline serum Cav-1 levels and hemorrhagic volume points to a potential usefulness of baseline serum Cav-1 levels to predict hemorrhagic volume, independently of rt-PA administration.