Abstract DP055: Novel Gene Expression Signature Distinguishes Acute Ischemic Stroke from Stroke Mimics

Introduction: Distinguishing acute ischemic stroke (AIS) from stroke mimics in the ED is a clinical challenge for emergency providers that leads to unnecessary intervention in mimics and delays in AIS treatment. A rapid gene expression–based blood test could reduce this uncertainty and improve treatment times. Existing RNA sequencing studies that compare AIS to healthy or at-risk controls yield large gene sets less specific to stroke. Few compare AIS to mimics acutely and none validate concise panels in real-time. We previously recruited a prospective stroke-code cohort at our center (74 strokes, 68 mimics; ICH excluded), with blinded vascular neurologist final diagnosis as reference. An mRNA gene expression panel was identified from sequencing at presentation (T0) and 24 hours (T24). Candidate genes showed maximal or minimal expression in AIS at T0, changed from T0 to T24 in AIS but not in mimics, and had relevant functions. Selection was also based on accuracy in classifying AIS versus mimic with the fewest biomarkers. Methods: To validate selected genes, the single-center VuEssence Stroke Trial (VEST) validation cohort prospectively enrolled additional adult ED stroke-code patients with known onset, this time including subsequent ICH. Conflicting study enrollment, or contraindications to phlebotomy or MR were VEST exclusions. Whole blood was collected in PAXgene tubes at presentation (T0) before any reperfusion therapy. A fast, chip-based qPCR system optimized for real-time detection measured expression of 21 of the prior derivation cohort candidate genes. Again, blinded vascular neurologists confirmed the diagnosis. Results: VEST enrolled 67 stroke-code patients (63% women, mean age 65.5 years). AIS patients were older than mimics (70.7 years, p=0.006) but were otherwise similar ( Fig. 1 ). A panel of 8 of 21 genes optimally distinguished AIS from mimics ( Fig. 2 ) with potential to rule in or rule out AIS (overall sensitivity: 0.90 [95% CI, 0.79–1.00]; specificity: 0.81 [95% CI, 0.68–0.94]). The final genes ( Fig. 3 ) function in glucose and vesicle transmembrane transport, nutrient response, vascular maintenance, innate immunity, calcium channels, thrombocythemia, and energy metabolism. Conclusions: Initial validation shows the feasibility of a rapid qPCR gene expression test to distinguish AIS from mimics in the acute hospital setting.