Epigenetic modification may play an important role in pathophysiology of ischemic stroke (IS) risk. MicroRNAs (miRNAs), which constitute one of the modes of epigenetic regulation, have been shown to be associated with a number of clinical disorders including IS. The purpose of this study was to investigate the miRNA profile in the peripheral blood mononuclear cells (PBMCs) of IS patients and compare it with stroke-free controls. Blood samples were obtained from 19 healthy age-gender-race matched individuals who served as controls to 20 IS patients. miRNA microarray analysis with RNA from PBMCs was performed and significantly dysregulated miRNAs common among IS patients were identified. We identified 117 miRNAs with linear fold values of at least ±1.5, of which, 29 were significantly altered (p value <0.05). Ingenuity Pathway Analysis (IPA) indicated a role for the dysregulated miRNAs in conditions relevant to IS (e.g., organismal injury and abnormalities, hematological disease and immunological disease). Pro-inflammatory genes like STAT3, interleukin (IL) 12A, and IL12B were some of the highly predicted targets for the dysregulated miRNAs. Notably, we further identified three common and significantly upregulated miRNAs (hsa-miR-4656, -432, -503) and one downregulated miRNA (hsa-miR-874) among all IS patients. Molecular interactive network analysis revealed that the commonly dysregulated miRNAs share several targets with roles relevant to IS. Altogether, we report dysregulation of miRNAs in IS PBMCs and provide evidence for their involvement in the immune system alteration during IS pathophysiology.

Background: Progression of aortic arch atheroma (AA) is associated with vascular events in patients with stroke or transient ischemic attack (TIA). Studies investigating effect of stroke prevention medication on AA progression are limited to post-cerebral segments that may not be related to stroke pathophysiology and do not use information from the relevant segments adjacent to the origin of the cerebral blood vessels. Methods: AA atheroma was detected on baseline transesophageal echocardiogram (TEE) in 167 consecutive patients who had stroke or TIA. Of these, 125 consented to a follow-up TEE at12 months. Adequate paired AA images were obtained in 117 (78 with strokes, 39 with TIAs), which allowed detailed measurements of plaques. On admission for their index stroke or TIA, patients were assessed for stroke risk factors and stroke prevention medications (Statins, Antiplatelet therapy and oral anticoagulant). We assessed three segments of the AA adjacent to the origin of the cerebral blood vessels for plaque thickness by TEE and analyzed the effect of medication using joint modeling, with due consideration to confounding covariates. The statistical paradigm included a permutation testing procedure to determine the significance of medication effect on plaque progression in the three segments in combination. Results: Using the specified statistical paradigm, it is evident that statin therapy is effective in arresting the AA progression; however, there is no significant change induced by anticoagulant therapy. The cleaned data, after removal of influential observations, shows even more significance for the statin therapy. The constrained hypothesis tests in both cases show a smaller p-value suggesting that the statin therapy may be effective in arresting the AA progression. Conclusions: In this preliminary study of stroke/TIA patients with AA atheroma on transesophageal echocardiogram, AA atheroma progression was arrested by statin therapy, without any significant change induced by anticoagulant therapy. The statistical paradigm with due consideration of all segments implicated in stroke pathophysiology may be used to test the effect of other stroke prevention medications on AA progression.

Introduction: Intravenous Tissue Plasminogen Activator (rTPA) is used to treat acute ischemic stroke (AIS). Early recanalization from this leads to better stroke outcomes, but the exact mechanism remains unknown. To clarify this, we correlated tissue perfusion and functional outcomes in acute stroke patients (AIS) who received rTPA to resting state default mode network (DMN) and task-positive (TPN) activities measured with fMRI. Following NIH stroke scale (NIHSS) assessments, patients underwent magnetic resonance imaging (MRI) scans during rTPA infusion (baseline), six hours post stroke and at 30d follow up visit.Results: Paired t-tests revealed that NIHSS at 6 hrs post stroke and at 30-days follow up significantly better compared to baseline, indicating improved functional outcomes. Changes in NIHSS were associated by significant changes in resting connectivity in TPN and DMN. In the TPN, both the undamaged Frontal Eye Field (FEF) and the undamaged intraparietal sulcus (IPS) node at the 6 hrs time point improved in connectivity with other TPN nodes compared to baseline. 30 days follow up resting connectivity of the DMN on the medial-prefrontal (MPF) node, and undamaged lateral parietal (LP) node, along with the damaged medial-temporalnode of TPN showed more robust correlations from baseline to 30 days follow up. The damaged IPS connectivity was the only measure that significantly correlated with NIHSS at the 6 hrs time point. No correlations with NIHSS were found at baseline or the 30 days time points with resting state or perfusion data. Conclusion:In this pilot study, we found that patients who received rTPA showed changes in resting state networks and functional outcomes over time. These findings point to an intriguing possibility, that the improvement of resting state networks may reflect improved efficiency of brain activity that is potentially related to functional outcomes in AIS patients who receive rTPA. As such, the improved functional connectivity measured with rsBOLD fMRI should be further explored as a potential predictive biomarker for rTPA response. Larger studies are needed to verify these findings.

Introduction and Hypothesis: Epidemiological studies have shown that migraine with aura (MA) is an independent risk factor for ischemic stroke. We assessed the hypothesis that migraine with aura is associated with specific ischemic stroke subtypes in the Atherosclerosis Risk In Communities (ARIC) study. Methods: We included 12844 participants among this ongoing prospective cohort of ARIC. All participants completed an in-person headache questionnaire: headaches are classified as MA, migraine without aura, or non-migraine headaches. All stroke diagnoses are based on computer-derived diagnosis and physician medical record review, with differences adjudicated by a second physician reviewer. Classification required evidence of sudden or rapid onset of neurological symptoms lasting ≥24 hours. Strokes were further classified according to etiologic subtype as thrombotic brain infarction, lacunar infarction, and cardioembolic stroke. Results: At the third ARIC study visit, 12.7% (1633) of participants had migraine and 8.5% (1093) had non-migraine headaches. 29% (472) of participants among migraineurs had MA. A total of 817 ischemic strokes occurred from1987-1989 to 2012, of which 51% (417) were thrombotic, 27% (224) were cardioembolic, and 22% (176) were lacunar stroke. Participants with MA had an increased odd of ischemic stroke, compared with participants with migraine without aura (unadjusted OR 2.4, 95% CI 1.6-3.6, P<0.0001). MA had a stronger association with cardioembolic stroke (OR 3.3, 95% CI: 1.4-8.0, p=0.009), compared with thrombotic stroke (OR 2.0, 95% CI: 1.2-3.4, p=0.01). There was no significant association between MA and lacunar stroke. Conclusions: Results from this prospective cohort are consistent with previous studies demonstrating an association between MA and ischemic stroke. Further, we report a stronger and significant association with the cardioembolic stroke subtype, with a significant but smaller association with thrombotic strokes. Etiology of the observed association is currently being evaluated in this population.

Background and Purpose: Stroke studies and trials frequently require identification and screening of specific stroke patients based on set selection criteria, missed by traditional methods that rely on physician reporting and discharge diagnosis codes. Our aim was to determine the utility of a smartphone application, Iodine, in screening and identifying cervical artery dissection (CAD) patients. Methods: Iodine is used to notify healthcare providers regarding specific patient populations for the purpose of process and quality improvement. Real-time patient data is sent to Iodine via feeds secured by encrypted virtual private network tunnels, and continuously evaluated against Iodine’s library of Alert rules. All communication between Iodine and users are encrypted, all data accesses are audited, and data is not stored on mobile devices, thereby ensuring Health Insurance Portability and Accountability Act compliance. CAD is an uncommon cause for stroke or TIA that can affect young patients without traditional risk factors. Recent advances in imaging, including MRI and CT angiogram, have led to more frequent identification of CAD. Based on the identification of the keyword “dissection” in all radiological reporting, we setup a notification to alert study investigators. These notifications were reviewed daily for enrollment in an ongoing prospective study COMPASS. These patients were compared with those identified by ICD-9 discharge diagnosis codes. Results: In a six month period between January 01, 2015 and June 30, 2015, 18 patients with CAD were identified through the Iodine out of 289 total dissection alerts. (Mean age ± SD = 57 ± 17, 50% male, 61% Caucasian, and 39% African American). Of these 18 patients, 3 died in-hospital and thus could not be identified using traditional methods. Of these, only 13 patients were identified through ICD-9 discharge diagnosis codes, out of 4683 total discharges. Iodine was found to have a significantly higher proportion of detecting CAD (χ2=146.1; p<0.0001). Conclusions: We report real time screening and identification of CAD using Iodine, which appears to be superior to traditional methods. This method may be successfully applied for other disease conditions for consecutive study patient identification.