Background and Purpose: The mechanisms linking systemic inflammation to poor outcome in ischemic stroke are not fully understood. The authors investigated if peripheral inflammation following reperfusion therapy leads to an increase in cerebral edema (CED), thus hindering the clinical recovery. Methods: We designed a single-center study conducted at Centro Hospitalar Universitário São João between 2017 and 2019. Inclusion criteria were being adult, having an anterior circulation acute ischemic stroke, and receiving reperfusion therapy. Neutrophil-to-lymphocyte, platelet-to-lymphocyte ratios, and the systemic inflammatory response syndrome criteria were determined. The presence and grade of CED were evaluated on the computed tomography performed 24 hours following event. The clinical outcomes included early neurological deterioration and functional dependence at 90 days. Adjusted odds ratio and 95% CI were obtained by ordinal and logistic regression models. Optimal cutoff values were defined using receiver operating characteristic analysis in the training cohort and validated in an independent data set. Results: Five hundred fifty-three patients were included. Neutrophil-to-lymphocyte increased with higher degrees of CED at 24 hours (adjusted odds ratio, 1.34 [1.09–1.68], P <0.01) and was associated with early neurological deterioration (adjusted odds ratio, 1.30 [1.04–1.63], P <0.05) and poor functional status at 90 days (adjusted odds ratio, 1.79 [1.28–2.48], P <0.01). Platelet-to-lymphocyte was not associated with the outcomes. Systemic inflammatory response syndrome was related to CED due to altered white blood cell counts. Neutrophil-to-lymphocyte was the best predictor with an area under the curve around 0.7. Neutrophil-to-lymphocyte ≥7 had and accuracy, sensitivity, and specificity around 60%. Conclusions: Increased systemic inflammation is linked to the severity of CED early after reperfusion therapy in stroke. Easily obtained inflammatory markers convey early warning alerts for patients at risk of severe neurological complications with an impact on long-term functional outcome. CED quantification should be included as an end point in proof-of-concept trials in immunomodulation in stroke.

BACKGROUND: Large vessel occlusion acute ischemic stroke prognosis improved following the 2015 endovascular therapy (EVT) trials. Blood-based biomarkers may improve outcome prediction. We aimed to assess plasma brain-derived tau (BD-Tau) performance in predicting post-EVT large vessel occlusion acute ischemic stroke outcomes. METHODS: We included 2 temporally independent prospective cohorts of anterior circulation in patients with large vessel occlusion acute ischemic stroke who successfully recanalized post-EVT. We measured plasma BD-Tau, GFAP (glial-fibrillary-acidic-protein), NfL (neurofilament-light-chain), and total-Tau upon admission, immediately, 24 hours, and 72 hours post-EVT. Twenty-four-hour neuroimaging and 90-day functional outcomes were independently assessed using the Alberta Stroke Program Early Computed Tomography Score (good outcome: >7 or unchanged) and the modified Rankin Scale (favorable outcome <3 or unchanged), respectively. Based on the first cohort (derivation), we built a multivariable logistic regression model to predict a 90-day functional outcome. Model results were evaluated using the second cohort (evaluation). RESULTS: In the derivation cohort (n=78, mean age=72.9 years, 50% women), 62% of patients had a good 24-hour neuroimaging outcome, and 45% had a favorable 90-day functional outcome. GFAP admission-to-EVT rate-of-change was the best predictor for early neuroimaging outcome but not for 90-day functional outcome. At admission, BD-Tau levels presented the highest discriminative performance for 90-day functional outcomes (area under the curve, 0.76 [95% CI, 0.65–0.87]; P <0.001). The model incorporating age, admission BD-Tau, and 24-hour Alberta Stroke Program Early Computed Tomography Score achieved excellent discrimination of 90-day functional outcome (area under the curve, 0.89 [95% CI, 0.82–0.97]; P <0.001). The score’s predictive performance was maintained in the evaluation cohort (n=66; area under the curve, 0.82 [95% CI, 0.71–0.92]; P <0.001). CONCLUSIONS: Admission plasma BD-Tau accurately predicted 90-day functional outcomes in patients with large vessel occlusion acute ischemic stroke after successful EVT. The proposed model may predict functional outcomes using objective measures, minimizing human-related biases and serving as a simplified prognostic tool for AIS.

COVID-19 is mainly characterized by respiratory manifestations. Nevertheless, neurologic complications have been described, including delirium, which appears to be frequent, prolonged, and severe. We conducted a retrospective analysis of demographic, clinical, and laboratory data of two cohorts: patients with COVID-19 admitted to the infectious disease intensive care unit (ID-ICU) and patients admitted to the ID-ICU with other respiratory infections in 2018-2019. Outcomes were defined as the presence, duration, and severity of delirium. Doses of antipsychotics used to control delirium were converted to equivalents and used as delirium severity. Logistics regression models were used to correlate COVID-19 with the outcomes. Ninety-nine patients with COVID-19 and 40 patients without COVID-19 were included. The mean age of the COVID-19 cohort was 63 years, with a male predominance. Delirium developed in 42%, with a median duration of 3 days and an equivalent dose of olanzapine use of 10 mg/day. In univariate analysis, COVID-19 was not associated with the development or different duration of delirium when compared with patients without COVID-19. There was an association between COVID-19 and severity of delirium in a binary logistic regression model controlled to confounding variables. COVID-19 is not associated with a higher prevalence or duration of delirium than in cohorts without COVID-19. However, it is associated with more severe forms of delirium.

We report an unusual case of cerebral venous thrombosis (CVT temporally associated with an otherwise asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. While coronavirus disease 2019 (COVID-19) has been associated with thrombotic events at different sites, most published cases report on symptomatic SARS-CoV-2 infection. We are confident this was an otherwise asymptomatic infection as the patient reported no symptoms and molecular and serological testing was consistent with infection more than 3weeks in the past. We believe this is an important report as it adds to the existing literature on thrombotic events in patients with COVID. It may even inform discussion of COVID vaccines and CVT since our patient, as those reported in association with vaccines, also had thrombocytopenia on admission.