Abstract
Objectives: Endothelial dysfunction (ED) has been linked to the pathogenesis of cerebral small vessel disease (SVD). We aimed to assess ED and cerebrovascular reactivity (CVR) in the patients with a diverse manifestation of SVD, with similar and extensive white matter lesions (WMLs, modified Fazekas scale grade ≥2), compared with a control group (CG) without the MRI markers of SVD, matched for age, gender, hypertension, diabetes, and to evaluate the change of CVR following 24 months.Methods: We repeatedly measured the vasomotor reactivity reserve (VMRr) and breath-holding index (BHI) of the middle cerebral artery (MCA) by the transcranial Doppler ultrasound (TCD) techniques in 60 subjects above 60 years with a history of lacunar stroke (LS), vascular dementia (VaD), or parkinsonism (VaP) (20 in each group), and in 20 individuals from a CG.Results: The mean age, frequency of the main vascular risk factors, and sex distribution were similar in the patients with the SVD groups and a CG. The VMRr and the BHI were more severely impaired at baseline (respectively, 56.7 ± 18% and 0.82 ± 0.39) and at follow-up (respectively, 52.3 ± 16.7% and 0.71 ± 0.38) in the patients with SVD regardless of the clinical manifestations (ANOVA, p > 0.1) than in the CG (respectively, baseline VMRr 77.2 ± 15.6%, BHI 1.15 ± 0.47, p < 0.001; follow-up VMRr 74.3 ± 17.6%, BHI 1.11 ± 0.4, p < 0.001). All the assessed CVR measures (VMRr and BHI) significantly decreased over time in the subjects with SVD (Wilcoxon's signed-rank test p = 0.01), but this was not observed in the CG (p > 0.1) and the decrease of CVR measures was not related to the SVD radiological progression (p > 0.1).Conclusions: This study provided evidence that the change in CVR measures is detectable over a 24-month period in patients with different clinical manifestations of SVD. Compared with the patients in CG with similar atherothrombotic risk factors, all the CVR measures (BMRr and BHI) significantly declined over time in the subjects with SVD. The reduction in CVR was not related to the SVD radiological progression.
Highlights
Small vessel disease (SVD) is one of the most important cerebral microangiopathy, responsible for the majority of lacunar stroke (LS), vascular dementia (VaD), and parkinsonism (VaP) cases (Pantoni, 2010)
To maximize the statistical power, we decided to analyze the equal groups of subjects and we recruited the consecutive patients with VaP and matched them in a 1:1 ratio with VaD, LS patients, and control groups (CGs) according to sex, age (±5 years), and the presence of diabetes and hypertension
The prevalence of the main comorbidities was similar in groups, but there were some differences in the laboratory examination findings: the CG had lower concentrations of homocysteine, showed a trend toward lower concentration of uric acid, and had higher levels of estimated glomerular filtration rate comparing with other subjects
Summary
Small vessel disease (SVD) is one of the most important cerebral microangiopathy, responsible for the majority of lacunar stroke (LS), vascular dementia (VaD), and parkinsonism (VaP) cases (Pantoni, 2010). The endothelium and vascular smooth muscle within the NVU forms the basis of blood-brain-barrier (BBB), and contribute to the neurovascular coupling that is the response of the cerebral vessel to the changes in neural activity (Attwell et al, 2010). We have found that the cerebral vasodilator responses to breath hold and hyperventilation were abnormal in the patients with VaD, LS, and VaP caused by SVD, and they were severely impaired when compared with the controls matched for the main vascular risk factors and free from the cerebrovascular events (Staszewski et al, 2019). Our study aimed to investigate the CVR changes over 24 months in the subjects with diverse manifestations of SVD (LS, VaD, and VaP), with similar and extensive radiological burdens of the disease and compare with a carefully selected CG without MRI markers of SVD, free of cerebrovascular events, and matched for major vascular comorbidities
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