Highlights COVID-19 disease is associated with stroke All strokes subtypes are seen in association with COVID-19, with ischemic stroke being most prevalent The most common etiology for ischemic stroke in SARS-CoV2 infection is cryptogenic Sex plays an important role in stroke outcomes in patients with COVID-19 disease Males have higher rates of ICU admission, in-hospital complications and more likely to have worse outcome at hospital discharge compare with females

The SARS-CoV-2 virus causing Coronavirus Disease 2019 (COVID-19) is a global pandemic with almost 30 million confirmed worldwide cases. Prothrombotic complications arising from those affected with severe symptoms have been reported in various medical journals. Currently, clinical trials are underway to address the questions regarding anticoagulation dosing strategies to prevent thrombosis for these critically ill patients. However, given the increasing use of therapeutic anticoagulation in patients admitted with COVID-19 to curtail this prothrombotic state, our institution has witnessed six cases of devastating intracranial hemorrhage as well as thrombosis leading to five fatalities and we examine their hospital course and anticoagulation used.

Fabry disease, an X-linked inborn error of metabolism, is characterized by multi-organ involvement including cardiac signs of left ventricular hypertrophy and abnormal intima-medial (IMT) thickening of arteries, progressive renal failure, neurological involvement, and more. The vitamin D receptor (VDR) and an enzyme producing vitamin D3 result in an autocrine loop with direct effects on blood vessels. The purpose of this study is to assess VDR polymorphisms (BsmI, FokI, ApaI, and TaqI) relative to clinically important disease parameters using a disease-specific severity score (MSSI) and haplotype analysis. There were statistically significant differences between females (43% of 74 patients) and males in MSSI total scores, and in general and neurologic sub-scores. There appears to be a protective effect of the TaqI tt genotype so that there were significantly lower scores in clinical categories between those with the tt genotype versus those with the TT genotype. Multivariate models of haplotypes with MSSI scores reveal that T-A-f-B and t-a-F-b haplotypes of the VDR gene polymorphisms are significantly associated with variation in the Fabry phenotype. Despite the limitations of using the MSSI score as a clinical correlate, these results are provocative and further studies in larger cohorts with more males are recommended.

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The use of medical imaging in the US has been steadily increasing over the last 2 decades. 1 For patients with suspected ischemic stroke, almost all have received computed tomography (CT) imaging of the brain at initial evaluation to exclude hemorrhage. Most patients subsequently undergo MRI within several days of symptoms. Current American Heart Association/American Stroke Association guidelines state that it is reasonable to obtain additional magnetic resonance imaging (MRI) after initial head imaging in cases in which initial imaging did not demonstrate infarction. 2

We present a case of a 33 year-old patient with glioblastoma (IDH wild type, MGMT unmethylated) who was diagnosed with COVID-19 pneumonia while undergoing chemotherapy. The patient did not have any medical comorbidities. He was clinically asymptomatic following surgery, completed concurrent phase of combined chemotherapy and radiation and was undergoing treatment with adjuvant temozolomide. He had radiographic improvement of the brain tumor (decreased size, contrast enhancement and T2 flair) after three cycles of adjuvant temozolomide. However, after cycle three the patient developed fever and abdominal pain. Evaluation in the emergency room revealed low absolute lymphocyte count (0.7 K/MM3), positive COVID-19 point of care test and CT chest revealed patchy peripheral bibasilar ground glass and consolidative opacities compatible with pulmonary infection, with viral etiology such as COVID. Symptoms resolved after 2 weeks. Due to active infection and leucopenia temozolomide was on hold for 1 month. He was considered cleared of infection after resolution of symptoms. Temozolomide was initiated after resolution of leucopenia. Patient continued to do well after administration of subsequent temozolomide cycles and repeat CT chest after 2 months revealed resolution of consolidation and no new areas of consolidation. Temozolomide was safely administered in this patient without reactivation of COVID-19 infection. He did not have any thrombotic events.

Introduction: Predicting outcome after mechanical thrombectomy (MT) for ischemic stroke due to LVO can inform prognosis and guide early management. Prior studies report heterogeneity in risk factors for poor outcome. Machine learning may identify patterns of poor outcome from diverse variables that are difficult to discern with conventional statistical methods. Methods: Using a retrospective database of 233 stroke patients (2015-20) who had MT for LVO, we created machine learning predictive models with clinical and imaging variables for the following 4 outcomes: decompressive craniectomy, discharge mRS ≥4, development of post-stroke cerebral edema with mass effect, and in-hospital mortality. We compared 10 learner models: AdaBoost, Tree, Random Forest, Neural Network, CN2 Rule Induction, Logistic Regression, Naïve Bayes, kNN, Stochastic Gradient Descent, and Support Vector Machine. Variables were ranked by 5 scoring methods: information gain, information gain ratio, gini decrease, chi-square, ReliefF, and fast correlation-based filter. A prediction model was created using the top 5 variables to maximize the area under the receiver operating characteristic curve and classification accuracy. Models were 5-fold cross validated. Analyses were conducted via Stata and Orange Data Mining. Results: Prediction model sets of 5 variables were generated for the 4 outcomes of interest. Infarction volume was most important for predicting decompressive craniectomy, discharge mRS ≥4, and in-hospital mortality. Cerebral edema was important for decompressive craniectomy, discharge mRS ≥4, and in-hospital mortality. Initial NIHSS was important for decompressive craniectomy, discharge mRS ≥4, and in-hospital mortality. Contrast staining on post-procedural CT was important for cerebral edema (χ 2 11.9) and in-hospital mortality (χ 2 21.8). Patient age was important for discharge mRS ≥4 and decompressive craniectomy. Conclusion: We identified prediction models consistent with established prognostic variables. Post-MT contrast staining is a novel and important predictor of poor outcome, which merits further research. In conclusion, machine learning can be used to create accurate prediction models for outcome after MT for ischemic stroke with LVO.

Introduction: Inflammation may play a central role in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (aSAH). Prostaglandins are inflammatory mediators that are elevated in aSAH and are synthesized by cyclooxygenase-2 (Cox-2). Celecoxib is a selective Cox-2 inhibitor with anti-inflammatory effects and good central nervous system penetration. In a mouse model of SAH, Cox-2 gene expression was found to be up-regulated in brain endothelial cells and celecoxib was found to limit Cox-2 up-regulation. We sought to evaluate the safety of celecoxib in patients with aSAH for future clinical studies. Methods: We used a matched case-control study to evaluate safety of celecoxib in aSAH patients. Our prospectively collected aSAH database (N=230) was retrospectively reviewed from 1/2010 - 2/2020. Celecoxib cases (N=13) and controls (N=217) were matched by closest Euclidean distance based on age and Glasgow Coma Scale (Figure 1). Each case was matched with 4 controls to maximize power based on closest Euclidean distance. Baseline characteristics for cases and controls were compared using a t-test or signed rank test for pairs. Categorical variables were compared using McNemar’s test for discordant pairs. A p value ≤.05 was considered significant for all univariate testing. Results are listed in Table 1. Discussion: No adverse events were associated with celecoxib use. At our center, celecoxib was primarily used in high grade aSAH for fever or headache. Maximum and mean temperature are statistically higher in the celecoxib group, consistent with the treatment indication. There were no differences in vasospasm prevalence, although our analysis is limited by sample size. Given the favorable safety profile, ease of drug availability, and plausible mechanism of therapeutic effect, celecoxib warrants further study in aSAH.