Association between post-treatment neuroimaging markers of cerebral small vessel disease and short-term efficacy of recombinant tissue plasminogen activator in acute stroke patients

Abstract

INTRODUCTION: Cerebral small vessel disease (CSVD) is prevalent in acute ischemic stroke (AIS) and may influence outcomes following intravenous thrombolysis with recombinant tissue plasminogen activator (r-tPA). This study examined associations between CSVD neuroimaging markers and early treatment response, defined as >/=4-point improvement on the National Institutes of Health Stroke Scale (NIHSS) at 24-48 hours. METHODS: In this retrospective cohort study at a tertiary stroke center (August 2020-November 2021), 154 AIS patients receiving r-tPA within 4.5 hours of onset underwent MRI within 48 hours after thrombolysis.CSVD markers (cerebral microbleeds CMBs, lacunar infarcts, white matter hyperintensities WMHs, enlarged perivascular spaces EPVSs) were assessed per STRIVE-2 standards, with total CSVD burden scored 0-4. Univariate and multivariable logistic regression analyzed associations with treatment response, adjusting for baseline NIHSS, sex, dyslipidemia, and visible infarction. RESULTS: Treatment response occurred in 70/154 patients (45.5%). CMBs were less frequent in responders (4.3%) versus non-responders (15.5%; p = 0.023). No significant differences were found for other markers or the total CSVD burden score. Multivariable analysis including baseline NIHSS confirmed that CMBs remained independently associated with reduced response (adjusted OR = 0.192; 95% CI = 0.046-0.798; p = 0.023). Dyslipidemia was more common in responders (p = 0.036). CONCLUSIONS: Among CSVD markers, only CMBs were associated with poorer early r-tPA response in AIS. Given the retrospective design, small number of CMB-positive patients, and use of post-treatment MRI, these findings should be considered hypothesis-generating. Future prospective studies with pre-treatment and serial imaging are warranted.