Resting State Functional Connectivity and Thrombolysis Mediated Reperfusion in Acute Ischemic Stroke: A Pilot Study

Abstract

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.