Compromised cerebrovascular reactivity related to presence of white matter hyperintensities in cryptogenic stroke with right-to-left shunts

Objective: This study investigates cerebrovascular reactivity (CVR) changes in cryptogenic stroke (CS) patients with right-to-left shunts (RLS) and evaluates the relationship between CVR and white matter hyperintensities (WMHs).

Methods: The breath-holding index (BHI), representing CVR, was measured from the middle cerebral artery (MCA) using the breath-holding method. WMHs were defined as clearly hyperintense areas on 3T magnetic resonance imaging (MRI), assessed separately as periventricular hyperintensities (PVH) and deep white matter hyperintensities (DWMH). RLS was diagnosed based on a contrast-enhanced transcranial Doppler (c-TCD) examination.

Results: Among 260 CS patients and 128 controls, BHI was significantly lower in CS groups (0.68±0.27 vs. 0.83±0.31, P<0.001), particularly in those with RLS (0.64±0.28 vs. 0.71±0.25,P=0.030). CS patients with WMHs exhibited lower BHI than those without WMHs (0.50±0.22 vs.0.60±0.35, P =0.012), and PVH showed lower BHI compared to DWMH (0.45±0.24 vs.0.58±0.16, P=0.003). A negative correlation was found between WMH severity and BHI (0.60±0.35 vs.0.51±0.21 vs.0.48±0.20 vs.0.38±0.28, P =0.025). Reduced BHI was an independent risk factor for WMHs (OR = 0.283; 95% CI = 0.081-0.995, P = 0.049).

Conclusion: CS patients, especially those with RLS, show reduced CVR, which correlates with the location and severity of WMHs. These findings suggest that RLS may significantly contribute to WMH development in CS patients.