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Patients with cancer and acute ischemic stroke (AIS) face high rates of recurrent thromboembolism or death.To examine whether hematologic and embolic biomarkers soon after AIS are associated with subsequent adverse clinical outcomes.We prospectively enrolled 50 adults with active solid tumor cancer and AIS at two hospitals from 2016 to 2020. Blood was collected 72-120 h after stroke onset. A 30-min transcranial Doppler (TCD) microemboli detection study was performed. The exposure variables were hematologic markers of coagulation (D-dimer, thrombin-antithrombin), platelet (P-selectin), and endothelial activation (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]), and the presence of TCD microemboli. The primary outcome was a composite of recurrent arterial/venous thromboembolism or death. We used Cox regression to evaluate associations between biomarkers and subsequent outcomes.During an estimated median follow-up time of 48 days (IQR, 18-312), 43 (86%) participants developed recurrent thromboembolism or death, including 28 (56%) with recurrent thromboembolism, of which 13 were recurrent AIS (26%). In unadjusted analysis, D-dimer (HR 1.6; 95% CI 1.2-2.0), P-selectin (HR 1.9; 95% CI 1.4-2.7), sICAM-1 (HR 2.2; 95% CI 1.6-3.1), sVCAM-1 (HR 1.6; 95% CI 1.2-2.1), and microemboli (HR 2.2; 95% CI 1.1-4.5) were associated with the primary outcome, whereas thrombin-antithrombin and thrombomodulin were not. D-dimer was the only marker associated with recurrent AIS (HR 1.2; 95% CI 1.0-1.5). Results were generally consistent in analyses adjusted for important prognostic variables.Markers of hypercoagulability and embolic disease may be associated with adverse clinical outcomes in cancer-related stroke.

Background Mobile stroke units (MSUs) are ambulances with staff and a computed tomographic scanner that may enable faster treatment with tissue plasminogen activator (t-PA) than standard m...

Objective The objective of this study was to examine the pathophysiology of ischemic stroke with cancer. Methods We conducted a prospective cross-sectional study from 2016 to 2020 at 2 hospitals. We enrolled 3 groups of 50 adult participants each. The main group included patients with active solid tumor cancer and acute ischemic stroke. The control groups included patients with acute ischemic stroke only or active cancer only. The patients with stroke-only and patients with cancer-only were matched to the patients with cancer-plus-stroke by age, sex, and cancer type, if applicable. The outcomes were prespecified hematological biomarkers and transcranial Doppler microemboli detection. Hematological biomarkers included markers of coagulation (D-dimer and thrombin-antithrombin), platelet function (P-selectin), and endothelial integrity (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], and soluble vascular cell adhesion molecule-1 [sVCAM-1]). Hematological biomarkers were compared between groups using the Kruskal-Wallis and Wilcoxon Rank-Sum tests. In multivariable linear regression models, we adjusted for race, number of stroke risk factors, smoking, stroke severity, and antithrombotic use. Transcranial Doppler microemboli presence was compared between groups using chi-square tests. Results Levels of all study biomarkers were different between groups. In univariate between-group comparisons, patients with cancer-plus-stroke had higher levels of D-dimer, sICAM-1, sVCAM-1, and thrombomodulin than both control groups; higher levels of thrombin-antithrombin than patients with cancer-only; and higher levels of P-selectin than patients with stroke-only. Findings were similar in multivariable analyses. Transcranial Doppler microemboli were detected in 32% of patients with cancer-plus-stroke, 16% of patients with stroke-only, and 6% of patients with cancer-only (p = 0.005). Interpretation Patients with cancer-related stroke have higher markers of coagulation, platelet, and endothelial dysfunction, and more circulating microemboli, than matched controls. ANN NEUROL 2021;90:159-169.

Background and Purpose— Comorbid cancer is common in patients with acute ischemic stroke (AIS). As blood mRNA profiles can distinguish AIS mechanisms, we hypothesized that cancer-related AIS would have a distinctive gene expression profile. Methods— We evaluated 4 groups of 10 subjects prospectively enrolled at 3 centers from 2009 to 2018. This included the group of interest with active solid tumor cancer and AIS and 3 control groups with active cancer only, AIS only, or vascular risk factors only. Subjects in the AIS-only and cancer-only groups were matched to subjects in the cancer-stroke group by age, sex, and cancer type (if applicable). Subjects in the vascular risk factor group were matched to subjects in the cancer-stroke and stroke-only groups by age, sex, and vascular risk factors. Blood was drawn 72 to 120 hours after stroke. Total RNA was processed using 3′ mRNA sequencing. ANOVA and Fisher least significant difference contrast methods were used to estimate differential gene expression between groups. Results— In the cancer-stroke group, 50% of strokes were cryptogenic. All groups had differentially expressed genes that could distinguish among them. Comparing the cancer-stroke group to the stroke-only group and after accounting for cancer-only genes, 438 genes were differentially expressed, including upregulation of multiple genes/pathways implicated in autophagy signaling, immunity/inflammation, and gene regulation, including IL (interleukin)-1, interferon, relaxin, mammalian target of rapamycin signaling, SQSTMI1 (sequestosome-1), and CREB1 (cAMP response element binding protein-1). Conclusions— This study provides evidence for a distinctive molecular signature in blood mRNA expression profiles of patients with cancer-related AIS. Future studies should evaluate whether blood mRNA can predict detection of occult cancer in patients with AIS. Clinical Trial Registration— URL: https://clinicaltrials.gov . Unique identifier: NCT02604667.

Introduction: One-tenth of patients with stroke have cancer. We previously identified mRNA profiles differentiating patients with stroke and cancer, stroke only, and cancer only. In this study, we investigated mRNA and microRNA (miRNA) transcriptomes to identify potential miRNA regulators that underlie the observed mRNA changes. Methods: We prospectively enrolled 4 groups of subjects at 3 centers from 2009-2020. This analysis included 41 subjects with ischemic stroke plus cancer, 42 subjects with ischemic stroke only, 28 subjects with cancer only, and 30 vascular risk factor controls. Stroke-only and cancer-only subjects were matched to stroke-plus-cancer subjects by age, sex, and cancer type. We performed miRNA and mRNA sequencing on blood drawn 72-120 hours after stroke. ANCOVA estimated differential expression of miRNA and mRNA between groups (FDR p1.2). Analyses were adjusted for time from stroke onset, sex, age, vascular risk factors and batch. Results: We identified differential expression in 36 miRNA and 264 corresponding mRNA targets between the stroke-plus-cancer and stroke-only groups after accounting for cancer-only expression (Fig 1). Immune and coagulation pathways, including complement, platelet glycoproteins, TGF-β, and mTOR signaling, were overrepresented in stroke-plus-cancer vs stroke-only subjects. T cell, B cell and platelet precursor-specific genes were also overrepresented in stroke-plus-cancer subjects. When compared to other groups, stroke-plus-cancer subjects had 230 unique mRNA encoding for transcriptional regulators, including those involving splicing, epigenetics, and mediator complex genes bridging transcription factors and RNA transcriptional machinery. Conclusion: Patients with stroke and cancer had distinct signatures of miRNA and target mRNA compared to stroke patients without cancer, supporting the hypothesis that cancer-related stroke is a unique subgroup of ischemic stroke.