Ischemic strokes in COVID-19: risk factors, obesity paradox, and distinction between trigger and causal association.

Background and purpose: Stroke has been described as a COVID-19 complication. However, its occurrence rate, risk factors, and causal relationships are still not well established. Methods: We describe the characteristics of confirmed COVID-19-related strokes among all cases of COVID-19 hospitalized in our health network, from November 1, 2020 to April 30, 2021. Risk factor analysis has been conducted for ischemic stroke (IS), which represents 92% of all confirmed cases of Covid-19-related strokes, and a "causal attribution to infection" classification is provided. Results: In all, 62/4105 hospitalized COVID-19 patients had an acute stroke (1.51%). Severe COVID-19 (OR 2.27-CI 1.06-4.77; p = 0.032), atrial fibrillation (OR 3.65-CI 1.63-7.98; p = 0.001), and ischemic heart disease (OR 4.590-CI 1.714-12.137; p = 0.002) proved to be independent risk factors for IS, while obesity was a protective factor (OR 0.90-CI 0.82-0.97; p = 0.012). COVID-19 had a causal role in 32.1% of IS cases, was a relevant cofactor in 28.6% of cases of IS, and was a possible trigger in 39.3% of events. Conclusion: Our stroke occurrence rate is consistent with other population-based reports (range 0.34-2.7%). Prespecified peculiar clinical and radiological features allow the distinction between "IS caused by COVID-19" and "IS triggered by COVID-19." Clinical history of vascular diseases and risk factors is crucial in determining the risk of IS in patients with COVID-19. However, the protective effect of a BMI > 30 kg/m2 seems to suggest an obesity paradox.

The use of alteplase, although safe, does not offer clear clinical advantages when mild stroke is non-disabling.

Introduction: It is unknown whether alteplase is effective and safe in patients with mild acute ischemic stroke (AIS). Determining whether symptoms are "disabling" or not is a crucial factor in the management of these patients. This study aimed to investigate the efficacy and safety of alteplase in patients with mild, non-disabling AIS. Methods: We included all consecutive patients admitted for AIS at our institution from January 2015 to May 2022 who presented a baseline NIHSS score of 0-5 and fit the criteria to receive intravenous thrombolysis. In order to select only subjects with non-disabling AIS, we excluded patients who scored more than 1 point in the following NIHSS single items: vision, language, neglect, and single limb. Patients who scored at least 1 point in the NIHSS consciousness item were excluded as well. This study is a retrospective analysis of a prospectively collected database. Results: After the application of the exclusion criteria, we included 319 patients, stratified into patients receiving and not receiving alteplase based on non-disabling symptoms. The two groups were comparable regarding demographic and clinical data. Rates of a 3-month favorable outcome, defined as a 3-month mRS score of 0-1, were similar, being 82.3% and 86.1% in the treated and untreated patients, respectively. Hemorrhagic complications and mortality occurred infrequently and were not affected by alteplase treatment. Discussion: This observational study suggests that the use of alteplase, although safe, is not associated with a better outcome in highly selected patients with non-disabling AIS.

Stress hyperglycemia as a modifiable predictor of futile recanalization in patients undergoing mechanical thrombectomy for acute ischemic stroke.

Introduction: Mechanical thrombectomy (MT) is the first line treatment in acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Approximately half of patients treated with MT does not have a favorable outcome 3 months after stroke. The aim of this study was to identify predictors of futile recanalization (FR) in patients with LVO treated with MT. Methods: A retrospective analysis of consecutive patients with acute ischemic stroke due to anterior circulation LVO who underwent MT. Patients with a TICI score of 2b or 3 were included. We distinguished two groups, FR and meaningful recanalization (MR), according to patients' disability three months after stroke (FR: mRS score > 2; MR: mRS score < 2). Results: We enrolled 238 patients (FR, n = 129, 54.2%; MR, n = 109, 45.8%). Age (OR 1.05, 95% CI 1.01-1.09, p = 0.012), female sex (OR 2.43, 95% CI 1.12-5.30, p = 0.025), stress hyperglycemia, as measured by the GAR index, (OR 1.17, 95% CI 1.06-1.29, p = 0.002), NIHSS at admission (OR 1.15, 95% CI 1.07-1.25, p = 0.001) and time from symptoms onset to MT (OR 1.01, 95% CI 1.00-1.01, p = 0.020) were independent predictors of FR. The AUC for the model combining age, female sex, GAR index, NIHSS at admission and time from symptoms onset to MT was 0.81 (95% CI 0.76-0.87; p < 0.001). The optimal GAR index cut-off score to predict FR was 17.9. Discussion: FR is common after MT. We recognized older age, female sex and baseline NIHSS as non-modifiable predictors of FR. On the other hand, time from symptoms onset to MT and stress hyperglycemia were modifiable pre- and post-MT factors, respectively. Any effort should be encouraged to reduce the impact of these modifiable predictors.

Failure of Therapeutic Anticoagulation in COVID-19 Patients With Acute Ischemic Stroke. A Retrospective Multicenter Study.

Background: Acute ischemic stroke (AIS) is a possible complication of coronavirus disease 2019 (COVID-19) infection. Although peculiar clinical features and underlying specific mechanisms of thrombogenesis have been suggested so far, there is no consensus on the appropriate vascular preventive drug regimen in patients with COVID-19. Aim and Methods: From a larger clinical series of consecutive acute ischemic strokes related to COVID-19 admitted to three cerebrovascular units in Northern Italy, herein, we describe the clinical features of a subgroup of patients in whom stroke occurred despite therapeutic anticoagulation. Results: A total of seventeen/80 AIS related to COVID-19 (21.2%) occurred in anticoagulated patients. Although no blood level was available for Direct Oral AntiCoagulant, the drug dosage was appropriate according to guidelines. Their National Institute of Health Stroke Scale (NIHSS) at admission was 12.0 (SD = 7.4) and 58.8% of them had evidence of large vessel occlusion. The case fatality rate was as high as 64.7%. Discussion and Conclusions: The occurrence of an anticoagulation failure seems to be increased in the setting of COVID-19 infection, with worse clinical outcomes if compared to non-COVID-19 related ischemic strokes. We discuss the diagnostic and therapeutic implications of such evidence, suggesting that some arterial thrombotic complications might be either resistant to or independent of the anticoagulation effect.