Background and Purpose: We sought to determine if biomarkers of inflammation and coagulation can help define coronavirus disease 2019 (COVID-19)–associated ischemic stroke as a novel acute ischemic stroke (AIS) subtype. Methods: We performed a machine learning cluster analysis of common biomarkers in patients admitted with severe acute respiratory syndrome coronavirus 2 to determine if any were associated with AIS. Findings were validated using aggregate data from 3 large healthcare systems. Results: Clustering grouped 2908 unique patient encounters into 4 unique biomarker phenotypes based on levels of c-reactive protein, D-dimer, lactate dehydrogenase, white blood cell count, and partial thromboplastin time. The most severe cluster phenotype had the highest prevalence of AIS (3.6%, P <0.001), in-hospital AIS (53%, P <0.002), severe AIS (31%, P =0.004), and cryptogenic AIS (73%, P <0.001). D-dimer was the only biomarker independently associated with prevalent AIS with quartile 4 having an 8-fold higher risk of AIS compared to quartile 1 ( P =0.005), a finding that was further corroborated in a separate cohort of 157 patients hospitalized with COVID-19 and AIS. Conclusions: COVID-19–associated ischemic stroke may be related to COVID-19 illness severity and associated coagulopathy as defined by increasing D-dimer burden.
Background: Most stroke recovery occurs by 90 days after onset, with proportional recovery models showing an achievement of about 70% of the maximal remaining recovery. Little is known about recovery during the acute stroke period. Moreover, data are described for groups, not for individuals. In this observational cohort study, we describe for the first time the daily changes of acute stroke patients with motor and/or language deficits over the first week after stroke onset. Methods: Patients were enrolled within 24-72 h after stroke onset with upper extremity hemiparesis, aphasia, or both, and were tested daily until day 7 or discharge with the upper-extremity Fugl-Meyer Assessment of Motor Recovery after Stroke, the Boston Naming Test, and the comprehension domain from the Western Aphasia Battery. Discharge scores, and absolute and proportional changes were examined using t-tests for pairwise comparisons and linear regression to determine relative contributions of initial impairment, lesion volume, and age to recovery over this period. Results: Thirty-four patients were enrolled: 19 had motor deficits alone, 8 had aphasia alone, and 7 had motor and language deficits. In a group analysis, statistically significant changes in absolute scores were found in the motor (p < 0.001) and comprehension (p < 0.001) domains but not in naming. Day-by-day recovery curves for individual patients displayed wide variation with comparable initial impairment. Proportional recovery calculations revealed that, on average, patients achieved less than 1/3 of their potential recovery by the time of discharge. Multivariate regression showed that the amount of variance accounted for by initial severity, age, and lesion volume in this early time period was not significant for motor or language domains. Conclusions: Over the first week after stroke onset, recovery of upper extremity hemiparesis and aphasia were not predictable on the basis of initial impairment, lesion volume, or age. In addition, patients only achieved about 1/3 of their remaining possible recovery based on the anticipated 70% proportion found at 90 days. These findings suggest that the complex interaction between poststroke structural repair, regeneration, and functional reorganization during the first week after stroke has yet to be elucidated.
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