scholarly journals Tadalafil may improve cerebral perfusion in small-vessel occlusion stroke—a pilot study

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Joakim Ölmestig ◽  
Ida R Marlet ◽  
Rasmus H Hansen ◽  
Shazia Rehman ◽  
Rikke Steen Krawcyk ◽  
...  
Keyword(s):  
Blood Flow ◽  
Endothelial Function ◽  
Oxygen Saturation ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Blood Oxygen ◽  
Blood Oxygen Saturation ◽  
Vessel Occlusion ◽  
Vessel Disease

Abstract New treatments for cerebral small-vessel disease are needed to reduce the risk of small-vessel occlusion stroke and vascular cognitive impairment. We investigated an approach targeted to the signalling molecule cyclic guanosine monophosphate, using the phosphodiesterase 5 inhibitor tadalafil, to explore if it improves cerebral blood flow and endothelial function in patients with cerebral small-vessel disease and stroke. In a randomized, double-blinded, placebo-controlled, cross-over pilot trial (NCT02801032), we included patients who had a previous (>6 months) small-vessel occlusion stroke. They received a single dose of either 20 mg tadalafil or placebo on 2 separate days at least 1 week apart. We measured the following: baseline MRI for lesion load, repeated measurements of blood flow velocity in the middle cerebral artery by transcranial Doppler, blood oxygen saturation in the cortical microvasculature by near-infrared spectroscopy, peripheral endothelial response by EndoPAT and endothelial-specific blood biomarkers. Twenty patients with cerebral small-vessel disease stroke (3 women, 17 men), mean age 67.1 ± 9.6, were included. The baseline mean values ± standard deviations were as follows: blood flow velocity in the middle cerebral artery, 57.4 ± 10.8 cm/s; blood oxygen saturation in the cortical microvasculature, 67.0 ± 8.2%; systolic blood pressure, 145.8 ± 19.5 mmHg; and diastolic blood pressure, 81.3 ± 9.1 mmHg. We found that tadalafil significantly increased blood oxygen saturation in the cortical microvasculature at 180 min post-administration with a mean difference of 1.57 ± 3.02%. However, we saw no significant differences in transcranial Doppler measurements over time. Tadalafil had no effects on peripheral endothelial function assessed by EndoPAT and endothelial biomarker results conflicted. Our findings suggest that tadalafil may improve vascular parameters in patients with cerebral small-vessel disease stroke, although the effect size was small. Increased oxygenation of cerebral microvasculature during tadalafil treatment indicated improved perfusion in the cerebral microvasculature, theoretically presenting an attractive new therapeutic target in cerebral small-vessel disease. Future studies of the effect of long-term tadalafil treatment on cerebrovascular reactivity and endothelial function are needed to evaluate general microvascular changes and effects in cerebral small-vessel disease and stroke.

scholarly journals Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review

2015 ◽  
Vol 36 (1) ◽  
pp. 72-94 ◽  
Author(s):  
Anna Poggesi ◽  
Marco Pasi ◽  
Francesca Pescini ◽  
Leonardo Pantoni ◽  
Domenico Inzitari
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Small Vessel Disease ◽  
Brain Magnetic Resonance Imaging ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Perivascular Spaces ◽  
Vessel Disease ◽  
Brain Changes

The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect small arteries, arterioles, venules, and capillaries of the brain. Magnetic resonance imaging (MRI) correlates of SVD are lacunes, recent small subcortical infarcts, white-matter hyperintensities, enlarged perivascular spaces, microbleeds, and brain atrophy. Endothelial dysfunction is thought to have a role in the mechanisms leading to SVD-related brain changes, and the study of endothelial dysfunction has been proposed as an important step for a better comprehension of cerebral SVD. Among available methods to assess endothelial function in vivo, measurement of molecules of endothelial origin in peripheral blood is currently receiving selective attention. These molecules include products of endothelial cells that change when the endothelium is activated, as well as molecules that reflect endothelial damage and repair. This review examines the main molecular factors involved in both endothelial function and dysfunction, and the evidence linking endothelial dysfunction with cerebral SVD, and gives an overview of clinical studies that have investigated the possible association between endothelial circulating biomarkers and SVD-related brain changes.

scholarly journals P4-078: REPRESENTATION OF BLOOD FLOW IN PERFORATING BASAL GANGLIA ARTERIES OF PATIENTS WITH CEREBRAL SMALL VESSEL DISEASE (CSVD) AT 7 TESLA MRI

2019 ◽  
Vol 15 ◽  
pp. P1304-P1304
Author(s):  
Valentina Perosa ◽  
Emrah Düzel ◽  
Tine Arts ◽  
Stefanie Schreiber ◽  
Anne Assmann ◽  
...  
Keyword(s):  
Blood Flow ◽  
Basal Ganglia ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
7 Tesla ◽  
Vessel Disease ◽  
7 Tesla Mri

scholarly journals Microstructural Predictors of Cognitive Impairment in Cerebral Small Vessel Disease and the Conditions of Their Formation

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 720
Author(s):  
Larisa A. Dobrynina ◽  
Zukhra Sh. Gadzhieva ◽  
Kamila V. Shamtieva ◽  
Elena I. Kremneva ◽  
Bulat M. Akhmetzyanov ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cognitive Impairment ◽  
White Matter ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Venous Blood Flow ◽  
Csf Flow ◽  
Vessel Disease

Introduction: Cerebral small vessel disease (CSVD) is the leading cause of vascular and mixed degenerative cognitive impairment (CI). The variability in the rate of progression of CSVD justifies the search for sensitive predictors of CI. Materials: A total of 74 patients (48 women, average age 60.6 ± 6.9 years) with CSVD and CI of varying severity were examined using 3T MRI. The results of diffusion tensor imaging with a region of interest (ROI) analysis were used to construct a predictive model of CI using binary logistic regression, while phase-contrast magnetic resonance imaging and voxel-based morphometry were used to clarify the conditions for the formation of CI predictors. Results: According to the constructed model, the predictors of CI are axial diffusivity (AD) of the posterior frontal periventricular normal-appearing white matter (pvNAWM), right middle cingulum bundle (CB), and mid-posterior corpus callosum (CC). These predictors showed a significant correlation with the volume of white matter hyperintensity; arterial and venous blood flow, pulsatility index, and aqueduct cerebrospinal fluid (CSF) flow; and surface area of the aqueduct, volume of the lateral ventricles and CSF, and gray matter volume. Conclusion: Disturbances in the AD of pvNAWM, CB, and CC, associated with axonal damage, are a predominant factor in the development of CI in CSVD. The relationship between AD predictors and both blood flow and CSF flow indicates a disturbance in their relationship, while their location near the floor of the lateral ventricle and their link with indicators of internal atrophy, CSF volume, and aqueduct CSF flow suggest the importance of transependymal CSF transudation when these regions are damaged.

Adverse effects of pre-existing cerebral small vessel disease on cognitive improvement after carotid endarterectomy

2019 ◽  
Vol 15 (6) ◽  
pp. 657-665 ◽  
Author(s):  
Jun Yoshida ◽  
Fumio Yamashita ◽  
Makoto Sasaki ◽  
Kunihiro Yoshioka ◽  
Shunrou Fujiwara ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
White Matter ◽  
Carotid Endarterectomy ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Cognitive Improvement ◽  
Vessel Disease

Background Although patients with improved cognition after carotid endarterectomy usually exhibit postoperative restoration of cerebral blood flow, less than half of patients with such cerebral blood flow change have postoperatively improved cognition. Cerebral small vessel disease on magnetic resonance imaging is associated with irreversible cognitive impairment. Aims The purpose of the present prospective study was to determine whether pre-existing cerebral small vessel disease affects cognitive improvement after carotid endarterectomy. Methods Brain MR imaging was performed preoperatively, and the number or grade of each cerebral small vessel disease was determined in 80 patients undergoing carotid endarterectomy for ipsilateral internal carotid artery stenosis (≥70%). The volume of white matter hyperintensities relative to the intracranial volume was also calculated. Brain perfusion single-photon emission computed tomography and neuropsychological testing were performed preoperatively and two months postoperatively. Based on these data, a postoperative increase in cerebral blood flow and postoperative improved cognition, respectively, were determined. Results Logistic regression analysis using the sequential backward elimination approach revealed that a postoperative increase in cerebral blood flow (95% confidence interval [CI], 10.74–3730.00; P = 0.0004) and the relative volume of white matter hyperintensities (95% CI, 0.01–0.63; P = 0.0314) were significantly associated with postoperative improved cognition. Although eight of nine patients with postoperative improved cognition exhibited both a relative volume of white matter hyperintensities <0.65% and a postoperative increase in cerebral blood flow, none of patients with a relative volume of white matter hyperintensities ≥0.65% had postoperative improved cognition regardless of any postoperative change in cerebral blood flow. Conclusion Pre-existing cerebral white matter hyperintensities on magnetic resonance imaging adversely affect cognitive improvement after carotid endarterectomy.

scholarly journals VENOUS BLOOD FLOW CHANGES IN AGE-RELATED CEREBRAL SMALL VESSEL DISEASE AS ASSESSED BY MRI

2020 ◽  
Vol 10 (2) ◽  
pp. 61-70
Author(s):  
M.V. Krotenkova ◽  
◽  
E.I. Kremneva ◽  
B.M. Akhmetzyanov ◽  
L.A. Dobrynina ◽  
...  
Keyword(s):  
Blood Flow ◽  
Small Vessel Disease ◽  
Venous Blood ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Venous Blood Flow ◽  
Vessel Disease ◽  
Age Related ◽  
Flow Changes

scholarly journals Association of Aortic Compliance and Brachial Endothelial Function with Cerebral Small Vessel Disease in Type 2 Diabetes Mellitus Patients: Assessment with High-Resolution MRI

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yan Shan ◽  
Jiang Lin ◽  
Pengju Xu ◽  
Mengsu Zeng ◽  
Huandong Lin ◽  
...  
Keyword(s):  
High Resolution ◽  
Endothelial Function ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Regression Analyses ◽  
Aortic Compliance ◽  
Vessel Disease ◽  
High Resolution Mri

Objective. To assess the possible association of aortic compliance and brachial endothelial function with cerebral small vessel disease in type 2 diabetes mellitus (DM2) patients by using 3.0 T high-resolution magnetic resonance imaging.Methods. Sixty-two clinically confirmed DM2 patients (25 women and 37 men; mean age:56.8±7.5years) were prospectively enrolled for noninvasive MR examinations of the aorta, brachial artery, and brain. Aortic arch pulse wave velocity (PWV), flow-mediated dilation (FMD) of brachial artery, lacunar brain infarcts, and periventricular and deep white matter hyperintensities (WMHs) were assessed. Pearson and Spearman correlation analysis were performed to analyze the association between PWV and FMD with clinical data and biochemical test results. Univariable logistic regression analyses were used to analyze the association between PWV and FMD with cerebral small vessel disease. Multiple logistic regression analyses were used to find out the independent predictive factors of cerebral small vessel disease.Results. Mean PWV was6.73±2.00 m/s and FMD was16.67±9.11%. After adjustment for compounding factors, PWV was found significantly associated with lacunar brain infarcts (OR = 2.00; 95% CI: 1.14–3.2;P<0.05) and FMD was significantly associated with periventricular WMHs (OR = 0.82; 95% CI: 0.71–0.95;P<0.05).Conclusions. Quantitative evaluation of aortic compliance and endothelial function by using high-resolution MRI may be potentially useful to stratify DM2 patients with risk of cerebral small vessel disease.

scholarly journals Relationship between cerebral blood flow and later cognitive decline in hypertensive patients with cerebral small vessel disease

2009 ◽  
Vol 32 (9) ◽  
pp. 816-820 ◽  
Author(s):  
Kazuo Kitagawa ◽  
Naohiko Oku ◽  
Yasuyuku Kimura ◽  
Yoshiki Yagita ◽  
Manabu Sakaguchi ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cognitive Decline ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Hypertensive Patients ◽  
Vessel Disease
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