Cerebral small vessel disease impairs dynamic cerebral autoregulation and mediates outcomes after stroke thrombectomy.

Abstract

Background: Cerebral small vessel disease (CSVD) is associated with poor outcomes after endovascular thrombectomy (EVT), but the underlying mechanism remains unclear. Impaired dynamic cerebral autoregulation (dCA), a fundamental function of cerebral microvasculature, has been proposed as a potential mediator but has not been systematically investigated.

Objectives: To determine whether CSVD burden influences functional outcomes through alterations in dCA.

Design: Observational-cohort-study.

Methods: We included 107 patients with anterior circulation large-vessel occlusion and successful EVT (expanded Thrombolysis in Cerebral Infarction ⩾2b). CSVD burden was assessed using standardised neuroimaging markers and dichotomised as none-to-mild (score 0-1) versus moderate-to-severe (score 2-3). dCA was assessed at two time points: early phase (T1, around 24 h post-EVT) and early subacute phase (T2, around 4-5 days post-EVT). Mediation analysis was performed to assess whether dCA changes mediated the association between CSVD burden and functional independence (modified Rankin Scale (mRS) score 0-2) at 90 days.

Results: Patients with moderate-to-severe CSVD (n = 38) demonstrated distinct dCA recovery patterns compared with those with none-to-mild CSVD (n = 69). While patients with none-to-mild CSVD exhibited improved very low frequency (VLF, 0.02-0.07 Hz) phase differences from T1 to T2 (+7.67° (-9.73, 35.53)), those with moderate-to-severe CSVD exhibited deterioration (-7.17° (-25.03, -0.74), p = 0.004), which remained significant after multivariable adjustment (β = -20.06, 95% confidence interval (CI): -37.78 to -0.90, p = 0.040). Functional independence was achieved in 73.9% of patients with none-to-mild CSVD versus 52.6% in those with moderate-to-severe CSVD (adjusted OR 0.25, 95% CI 0.09-0.74, p = 0.012). Mediation analysis revealed that VLF phase changes in the affected side mediated 24.48% of the association between CSVD burden and functional outcome (average causal mediation effect: -7%, p < 0.001; total effect: -29%, p = 0.020).

Conclusion: Higher CSVD burden was associated with worse functional outcomes after EVT, partially explained by impaired dCA. Patients with moderate-to-severe CSVD exhibited deteriorating dCA, whereas those with none-to-mild CSVD showed progressive improvement. Larger powerful studies are warranted to validate these findings and elucidate underlying mechanisms.

Trial registration: ClinicalTrials.gov, NCT06361017.