Utilizing RNA sequencing to identify gene expression markers of stroke-causing thrombi origin: A pilot study.

INTRODUCTION: Stroke embolic source have an unknown origin in 30-40% of cases. Mechanical thrombectomy for acute large vessel occlusion stroke has provided us with a method to directly retrieve the thrombi from patients for analysis. By collecting stroke-causing thrombi from known sources, we can then use high-throughput RNA sequencing (RNAseq) technology to directly measure the gene expression signatures of these clots. This may allow us to identify genetic markers to predict the cause of cryptogenic embolism. METHODS: This is a prospective study in which RNAseq was used to analyze cerebral thrombi retrieved by mechanical thrombectomy devices in acute ischemic stroke patients. Samples were separated into two groups based on known stroke thrombus etiology, including Carotid group (patients with ipsilateral >70% carotid stenosis) and Atrial fibrillation (AF) group (patients with atrial fibrillation). Gene expression was compared by RNAseq analysis between the groups. RESULTS: From October 2016 to September 2017, 8 thrombi (4 in Carotid group, 4 in Afib group) were included in this study. There were 131 genes that were significantly up- or down-regulated between the two groups defined as a false discovery rate ≤ 0.05 and a fold change ≥ 2. Twenty-six genes were selected as candidate gene biomarkers based on the criteria in the methods section. Candidate genes HSPA1B, which encodes a heatshock protein, and GPRC5B, which encodes a G-protein, showed the greatest fold differences in expression between the two groups. CONCLUSION: This study has shown that RNA sequencing of acute ischemic stroke thrombi is feasible and indentified potential novel biomarkers for identifying stroke-causing thrombi origin, especially in cryptogenic stroke.

Vascular health across young adulthood and midlife cerebral autoregulation, gait, and cognition.

INTRODUCTION: To test the association of vascular health (VH) across young adulthood with midlife dynamic cerebral autoregulation (dCA), gait, and cognition; and to test whether dCA is a modifying factor. METHODS: We studied 196 participants from the Coronary Artery Risk Development in Young Adults cohort who were followed over 30 years. VH was assessed at each visit according to American Heart Association recommendations. At year 30, dCA was measured using transcranial Doppler ultrasound and several gait and cognitive domains were assessed. RESULTS: Worse VH from baseline through year 7, but not at year 30, was associated with less efficient dCA (all P < .05). Worse VH at all visits was associated with slower gait speed, and at year 7 with worse executive and global cognition (all P < .05). The association of baseline VH and midlife gait, but not cognition, was moderated by dCA (interaction P < .05). CONCLUSIONS: VH as early as young adulthood may influence midlife brain health, and dCA may modify this relationship.

2D parametric contrast time-density analysis for the prediction of complete aneurysm occlusion at six months' post-flow diversion stent.

OBJECTIVE: Indications for the treatment of cerebral aneurysms with flow diversion stents are expanding. The current aneurysm occlusion rate at six months ranges between 60 and 80%. Predictability of complete vs. partial aneurysm occlusion is poorly defined. Here, we evaluate the angiographic contrast time-density as a predictor of aneurysm occlusion rate at six months' post-flow diversion stents. METHODS: Patients with unruptured cerebral aneurysms proximal to the internal carotid artery terminus treated with single flow diversion stents were included. 2D parametric parenchymal blood flow software (Siemens-Healthineers, Forchheim, Germany) was used to calculate contrast time-density within the aneurysm and in the proximal adjacent internal carotid artery. The area under the curve ratio between the two regions of interests was assessed at baseline and after flow diversion stents deployment. The area under the curve ratio between completely vs. partially occluded aneurysms at six months' follow-up was compared. RESULTS: Thirty patients with 31 aneurysms were included. Mean aneurysm diameter was 8 mm (range 2-28 mm). Complete occlusion was obtained in 19 aneurysms. Younger patients (P = 0.006) and smaller aneurysms (P = 0.046) presented higher chance of complete obliteration. Incomplete occlusion of the aneurysm was more likely if the area under the curve contrast time-density ratio showed absolute (P = 0.001) and relative percentage (P = 0.001) decrease after flow diversion stents deployment. Area under ROC curve was 0.85. CONCLUSION: Negative change in the area under the curve ratio indicates less contrast stagnation in the aneurysm and lower chance of occlusion. These data provide a real-time analysis after aneurysm treatment. If validated in larger datasets, this can prompt input to the surgeon to place a second flow diversion stents.