Evaluation of right-to-left shunt on contrast-enhanced transcranial Doppler in patent foramen ovale-related cryptogenic stroke: Research based on imaging.

BACKGROUND: Cardiogenic embolism caused by patent foramen ovale (PFO) is a common etiology of cryptogenic stroke (CS), particularly in young and middle-aged patients. Studies about right-to-left shunt (RLS) detection using contrast-enhanced transcranial Doppler (c-TCD) are numerous. According to the time phase and number of microbubbles detected on c-TCD, RLS can be classified and graded. We hypothesized that the characteristics of an infarction lesion on diffusion-weighted imaging differs when combining the type and grade of RLS on c-TCD in patients with PFO-related CS. AIM: To explore the characteristics of infarction lesions on diffusion-weighted imaging when combining the RLS type and grade determined by c-TCD. METHODS: We retrospectively evaluated CS patients from August 2015 to December 2019 at a tertiary hospital. In total, 111 PFO-related CS patients were divided according to whether RLS was permanent (microbubbles detected both at resting state and after the Valsalva maneuver) or latent (microbubbles detected only after the Valsalva maneuver) on c-TCD. Each group was subdivided into small, mild and large RLS according to the grade of shunt on c-TCD. A normal control group was composed of 33 patients who suffered from simple dizziness. Intragroup and intergroup differences were analyzed in terms of clinical, laboratory and diffusion-weighted imaging lesion characteristics. The correlation between RLS grade evaluated by c-TCD and size of PFO determined by transesophageal echocardiography were also analyzed. RESULTS: In 111 patients with PFO-related CS, 68 had permanent RLS and 43 had latent RLS. Clinical characteristics and laboratory tests were not significantly different among the permanent RLS, latent RLS and normal control groups. The proportion of patients with multiple territory lesions in the permanent RLS group (50%) was larger than that in the latent RLS group (27.91%; P = 0.021). Posterior circulation was more likely to be affected in the latent RLS group than in the permanent RLS group (30.23% vs 8.82%, P = 0.004). Permanent-large and latent-large RLS were both more likely to be related to multiple (P trend = 0.017 and 0.009, respectively), small (P trend = 0.035 and 0.006, respectively) and cortical (P trend = 0.031 and 0.033, respectively) lesions. The grade of RLS evaluated by c-TCD was correlated to the size of PFO determined by transesophageal echocardiography (r = 0.758, P < 0.001). CONCLUSION: Distribution of the infarct suggested the possible type of RLS. Multiple, small and cortical infarcts suggest large RLS induced by a large PFO.

Specific matrix metalloproteinases and calcification factors are associated with the vulnerability of human carotid plaque.

The rupture of atherosclerotic plaque provokes the majority of acute cerebrovascular events. Studies have demonstrated that various matrix metalloproteinases (MMPs) may promote atherosclerotic plaque progression and rupture. However, results have been incongruous and the mechanisms of this remain obscured. Therefore, in the current study, carotid plaques were characterized by assessing the levels of MMPs and calcification factors, and evaluating their association with plaque vulnerability. Human carotid plaques were obtained from carotid endarterectomies, and classified into stable and vulnerable groups by ultrasonography and histological analyses. The mRNA and protein levels of MMPs, vascular endothelial growth factor (VEGF), bone sialoprotein 2 (BSP) and osteopontin were investigated by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. Immunohistochemistry was used to localize MMP-2 and MMP-14 in stable and vulnerable plaques. The activation of various associated signaling pathways was also investigated using western blotting. The mRNA levels of MMP-2, -7, -9 and -14 were elevated in vulnerable plaques, among which expression of MMP-2 and -14 were the highest. Consistent with the mRNA levels, the protein levels of MMP-2 and -14 were also elevated. Immunohistochemistry also demonstrated positive staining of MMP-2 and MMP-14 in vulnerable plaques. Factors that indicate neovascularization and calcification, including VEGF and BSP, were concurrently elevated in vulnerable plaques. In addition, the protein levels of extracellular regulated kinase (ERK) and protein kinase C (PKC) were upregulated in vulnerable plaques. The current study provides novel insights into the MMP profiles of vulnerability plaques, and may assist in the development of novel methods for the diagnosis of plaque vulnerability and the prevention of plaque rupture.

Intraoperative microvascular Doppler monitoring in intracranial aneurysm surgery.

BACKGROUND: Surgical treatment of intracranial aneurysms is often compromised by incomplete exclusion of the aneurysm or stenosis of parent vessels. Intraoperative microvascular Doppler (IMD) is an attractive, noninvasive, and inexpensive tool. The present study aimed to evaluate the usefulness and reliability of IMD for guiding clip placement in aneurysm surgery. METHODS: A total of 92 patients with 101 intracranial aneurysms were included in the study. IMD with a 1.5-mm diameter, 20-MHz microprobe was used before and after clip application to confirm aneurysm obliteration and patency of parent vessels and branching arteries. IMD findings were verified postoperatively with digital subtraction angiography (DSA) or dual energy computed tomography angiography (DE-CTA). Ninety consecutive patients, harboring 108 aneurysms, who underwent surgery without IMD was considered as the control group. RESULTS: The microprobe detected all vessels of the Circle of Willis and their major branches. Clips were repositioned in 24 (23.8%) aneurysms on the basis of the IMD findings consistent with incomplete exclusion and/or stenosis. IMD identified persistent weak blood flow through the aneurismal sac of 11 of the 101 (10.9%) aneurysms requiring clip adjustment. Stenosis or occlusion of the parent or branching arteries as indicated by IMD necessitated immediate clip adjustment in 19 aneurysms (18.8%). The mean duration of the IMD procedure was 4.8 minutes. The frequency of clip adjustment (mean: 1.8 times per case) was associated with the size and location of the aneurysm. There were no complications related to the use of IMD, and postoperative angiograms confirmed complete aneurysm exclusion and parent vessel patency. About 8.3% (9/108) aneurysms were unexpectedly incompletely occluded, and 10.2% (11/108) aneurysms and parent vessel stenosis without IMD were detected by postoperative DSA or DE-CTA. IMD could reduce the rate of residual aneurysm and unanticipated vessel stenosis which demonstrated statistically significant advantages compared with aneurysm surgery without IMD. CONCLUSION: IMD is a safe, easily performed, reliable, and valuable tool that is suitable for routine use in intracranial surgery, especially in complicated, large, and giant aneurysms with wide neck or without neck.