The current status and future trends of BET research in oncology.

Background: BET family proteins are important epigenetic and transcriptional regulators involved in the control of tumorigenesis and development and have become important targets for cancer therapy. However, there is no systematic bibliometric analysis in this field. A visual analysis of the research hotspots and trends of BET is helpful to understand the future development direction. Method: We used CiteSpace, VOSviewer, and Excel to visualize and analyze the trends regarding authors, journals, countries or regions, highly cited papers, and keywords in the field. Result: The results included a total of 946 publications. There are many more papers on BET proteins published since 2013. The papers are mainly from 44 countries, led by the U.S. and China. A total of 7381 authors were identified, among which Bradner, J.E. had the greatest number of articles and the greatest influence. Cancer Discovery was the journal with the most citations per article. Our analysis identified the most influential papers in the field, including highly cited papers and citation burst references. The most frequent keywords included 'expression', 'c-Myc', 'cancer', 'BRD4', 'BET inhibition', 'resistance', 'differentiation', and 'JQ1', which represent the focus of current and developing research fields. Conclusion: Research on BET is thriving. Collaboration and exchanges between countries and institutions must be strengthened in the future, and the mechanisms of BET-related pathways, the relationship between BET and various diseases, and the development of new BET inhibitors have become the major focus of current research and the trend of future research.

SDF-1/CXCR4 axis participants in the pathophysiology of adult patients with moyamoya disease.

BACKGROUND: Moyamoya disease (MMD) is characterized by an abundance of moyamoya vessels; however, the precise mechanism driving the spontaneous angiogenesis of these compensatory vessels remains unclear. Previous research has established a link between the stromal cell-derived factor-1 (SDF-1)/ CXC receptor 4 (CXCR4) axis and angiogenesis under hypoxic conditions. Nevertheless, the alterations in this axis within the cerebrospinal fluid, arachnoid membranes and vascular tissue of MMD patients have not been fully investigated. METHODS: Our study enrolled 66 adult MMD patients and 61 patients with atherosclerotic vascular disease (ACVD). We investigated the SDF-1 concentration in cerebrospinal fluid (CSF) and CXCR4 expression level on the arachnoid membranes and vascular tissue. We utilized enzyme-linked immunosorbent assay and immunohistochemistr. Additionally, we cultured and stimulated human brain microvascular endothelial cells (HBMECs) and smooth muscle cells (SMCs) under oxygen and glucose deprivation (OGD) conditions followed by reoxygenation, to examine any changes in the SDF-1/CXCR4 axis. RESULTS: The results demonstrated an elevation in the level of SDF-1 in CSF among MMD patients compared to those with ACVD. Moreover, the expression of CXCR4 in arachnoid membranes and vascular tissue showed a similar trend. Furthermore, the content of CXCR4 in HBMECs and SMCs increased with the duration of ischemia and hypoxia. However, it was observed that the expression of CXCR4 decreased at OGD/R 24h compared to OGD 24h. The temporal pattern of SDF-1 expression in HBMECs and SMCs mirrored that of CXCR4 expression. CONCLUSION: These findings indicate a critical role for the SDF-1/CXCR4 axis in the angiogenesis of moyamoya disease.

Comparison of IMD and ICG videoangiography in combined bypass surgery: a single-center study.

BACKGROUND: Superficial temporal artery-middle cerebral artery (STA-MCA) bypass combined with an encephaloduromyosynangiosis (EDMS) had gained significant role in treating chronic cerebral ischemia. Invasiveness and costs of intraoperative digital subtraction angiography (DSA) limited its application in operations. OBJECTIVE: To find the reliable parameters for determining bypass patency with intraoperative micro-Doppler (IMD) sonography and compare the diagnostic accuracy of indocyanine green (ICG) videoangiography with IMD in combined bypass. METHOD: One hundred fifty bypass procedures were included and divided into patent and non-patent groups according to postoperative computed tomography angiography (CTA) within 72 h. The surgical process was divided into four phases in the following order: preparation phase (phase 1), anastomosis phase (phase 2), the temporalis muscle closure phase (phase 3), and the bone flap closure phase (phase 4). The IMD parameters were compared between patent and non-patent groups, and then compared with the patency on CTA by statistical analyses. IMD with CTA, ICG videoangiography with CTA, IMD with ICG videoangiography were performed to assess bypass patency. The agreement between methods was evaluated using kappa statistics. RESULTS: No significant differences of baseline characteristics were found between patent and non-patent group. Parameters in the STA were different between patent and non-patent groups in phases 2, 3, and 4. In patent group, Vm was apparently higher and PI was lower in phases 2, 3, and 4 compared with phase 1 (P < .001). In non-patent group, no differences of Vm and PI were found within inter-group. The best cutoff value of IMD in the STA to distinguish patent from non-patent bypasses was Vm in phase 4 > 17.5 cm/s (sensitivity 94.2%, specificity 100%). In addition, the agreement for accessing bypass patency was moderate between ICG videoangiography and CTA (kappa = 0.67), IMD and ICG videoangiography (kappa = 0.73), and good between IMD and CTA (kappa = 0.86). CONCLUSION: ICG videoangiography could directly display morphology changes of bypass. IMD could be used for providing half-quantitative parameters to assess bypass patency. Vm in phase 4 > 17.5 cm/s suggesting the patency of bypass on CTA would be good. Also, compared with ICG videoangiography, IMD had more accuracy.

Resection of ruptured aneurysm associated with bilateral anomalous posterior inferior cerebellar anastomotic arteries: case report and review of literature.

Introduction: Aneurysms on the posterior inferior cerebellar artery (PICA) may not be the major part of intracranial aneurysm. Especially, an aneurysm located on the bilateral posterior inferior cerebellar anastomotic artery has abnormal anatomical characteristics in the vessel wall and then causes stroke including subarachnoid hemorrhage. This case report explores the direct resection of a ruptured aneurysm associated with the bilateral anomalous anastomotic artery of PICA. Methods: The case report discusses a 53-year-old woman who suffered from sudden severe headache and vomiting for more than 3 h admitted to our hospital. Emergency computed tomography (CT) revealed subarachnoid hemorrhage (SAH) in the third and fourth ventricles. Preoperative 3 Dimensions-digital subtraction angiography (3-D DSA) indicated a ruptured aneurysm located on the bilateral posterior inferior cerebellar anastomotic artery. Postoperative pathological findings indicated the characteristics of parent artery PICA and control aneurysm. The authors performed an overview of PICA aneurysms with anomalous variation in the Pubmed, Web of Science, and Medline databases. The search was until 1 August 2023. Related terms "posterior inferior cerebellar artery" And "aneurysm" AND "anatomical variants" were used to search the review. The reasons for anomalous variation anastomosis between bilateral PICAs were analyzed. Results: The aneurysm was resected successfully. Post-operative 3-D DSA revealed the disappearance of the aneurysm. The vessel wall of anastomotic PICA showed neovascularized hyperplasia, abnormal arrangement of smooth muscle, CD31+ endothelial cells, and SMA+ smooth muscle cells. In contrast, when it came to aneurysm, the wall at the location of the fracture thinned, which could be used to explain that the local nodular protrusion was formed and CD31+ endothelial cells existed. No neurological deficits were found at her 1-year follow-up visit (mRS score of 0). Conclusion: Direct resection of ruptured aneurysm associated with bilateral anomalous posterior inferior cerebellar anastomotic arteries was an effective treatment and careful consideration of the anatomical characteristics concerning the interesting aneurysm and the variant PICA was critical for sate treatment. Also, the literature on the lesion was reviewed.

Corrigendum: The correlation between collagen types and ultrasound feature score in evaluating the vulnerability of carotid artery plaque.

[This corrects the article DOI: 10.3389/fcvm.2021.756424.].

Data-Independent Acquisition-Based Serum Proteomic Profiling of Adult Moyamoya Disease Patients Reveals the Potential Pathogenesis of Vascular Changes.

Moyamoya disease (MMD) is a chronic cerebrovascular disease with unknown etiology. The pathogenesis of vascular changes remains unclear. Ischemic and hemorrhagic adult MMD patients and healthy volunteers were enrolled to collect serum for data-independent acquisition (DIA)-based proteomic analysis and ELISA validation. DIA serum proteomic revealed that apolipoprotein C-I (APOC1), apolipoprotein D (APOD), and apolipoprotein A-IV (APOA4) were decreased. The reductases glutathione S-transferase omega-1 (GSTO1) and peptidyl-prolyl cis-trans isomerase A (PPIA) were upregulated, and ADAMTS-like protein 4 (ADAMTSL4) was downregulated in both ischemic and hemorrhagic MMD. Afamin (AFM) and transforming growth factor-beta-induced protein ig-h3 (TGFBI) increased in ischemic patients but decreased in hemorrhagic patients. Serum ELISA results confirmed that APOA4, APOC1, and APOD were decreased compared to controls. Then, we retrospectively analyzed biochemical indexes of 200 MMD patients. A total of 54 enrolled MMD patients showed decreased total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-c). APOA4, APOC1, and APOD were vital factors in the HDL decrease in MMD patients. Lipoprotein dysfunction in MMD patients is involved in MMD. Intimal thickening by enhanced adhesion, middle layer vascular smooth muscle cell migration, and decreased lipid antioxidant function represented by HDL are potential pathogeneses of vascular changes in MMD.

Segmented carotid endarterectomy for treatment of Riles type 1A common carotid artery occlusion.

OBJECTIVE: Common carotid artery occlusion (CCAO) is a rare cause of cerebrovascular events. Symptomatic lesions are resistant to medical treatment and revascularization is often required, but there is no consensus on the treatment of CCAO at present. Riles type 1A CCAO is most likely to benefit from revascularization because it has patent outflow tract (internal carotid artery) which was supplied by patent external carotid artery (ECA) from collateral circulation. We described a novel surgical technique improved on the basis of the carotid endarterectomy (CEA) for treatment of Riles type 1A CCAO. METHODS: We rigorously screened ten patients with symptomatic Riles type1A CCAO for surgery from January 2017 to May 2019 and performed a full preoperative assessment of the inadequate collateral circulation compensation. Moreover, we retrospectively reviewed our experience of the segmented CEA in the treatment of them in our single center. RESULTS: Segmented CEA was performed on the left side in four cases and on the right side in six cases. The technical success rate of the procedure was 100%. Primary suture was used in nine cases. Only one patient (right CCAO) who had a history of neck radiotherapy was treated by the patch CEA. The mean temporary blocking time during surgery was 52.8 ± 9.15 min. The mean temporary blocking time for treating the upper segment of the common carotid artery (CCA) was 11.1 ± 2.64 min. In the postoperative period, cerebral perfusion on the ipsilateral site improved in all patients, myocardial infarction occurred in one patient, and recurrent laryngeal nerve damage occurred in another. No ischemic events or re-occlusion or restenosis (> 50%) of the treated CCA occurred during the mean follow-up of 32.6 ± 9.3 months. The preoperative mean modified Rankin Scale (mRS) score was 1.9 (range, 1-3; median, 2). At last follow-up for all patients, the mRS score was 1 (range, 0-3; median, 1). CONCLUSION: Segmented CEA, which utilizes the compensatory effect of collateral circulation, is an effective and safe technique to treat patients suffering from Riles type 1A CCAO with hemodynamic cerebrovascular compromise.

Association of Carotid Plaque Vulnerability and Cardiovascular Risk Factors in Patients Undergoing Carotid Endarterectomy.

BACKGROUND: The association between high-risk cardiovascular factors and atherosclerotic is well established. However, whether plaque vulnerability is related to specific cardiovascular risk factors remains unknown. The association between plaque vulnerability and cardiovascular risk factors was evaluated in plaques removed in a carotid endarterectomy. METHODS: Consecutive subjects scheduled for a carotid endarterectomy were recruited. All patients' baseline characteristics, risk factors, laboratory results, cardiovascular disease history, and medication use history were collected preoperatively. Histopathologic features within the vulnerable plaques were analyzed postoperatively. Risk factors for plaque vulnerability were assessed by univariate and multivariate analyses with adjustment for potential confounders. RESULTS: A total of 128 carotid plaques were removed during the carotid endarterectomy. On multivariate analysis, hypertension (odds ratio [OR] 5.971, 95% confidence interval [CI] 1.959-18.203, P = 0.002) and dyslipidemia (OR 3.822, 95% CI 1.317-11.089, P = 0.014) were independently associated with plaque vulnerability. Hypertension was independently associated with the presence of a ruptured fibrous cap (OR 6.122, 95% CI 2.318-16.166, P < 0.001), intraplaque hemorrhage (OR 3.535, 95% CI 1.551-8.055, P = 0.003), and a large lipid core (OR 2.335, 95% CI 1.053-5.180, P = 0.037). The incidence of having a large lipid core was increased by 3.216-fold in patients with dyslipidemia (95% CI 1.409-7.340, P = 0.006). When the multivariate analysis was restricted to symptomatic patients, hypertension (OR 5.005, 95% CI 1.294-19.350, P = 0.020) was the most significant risk factor associated with vulnerable plaque. CONCLUSION: The composition heterogeneity in the atherosclerotic plaque was significantly correlated to specific cardiovascular risk factors.

The Correlation Between Collagen Types and Ultrasound Feature Score in Evaluating the Vulnerability of Carotid Artery Plaque.

Objectives: To investigate whether ultrasound score has clinical value in identifying carotid artery-vulnerable plaque and the impacts of collagen distribution on the stability of plaque. Materials and Methods: Standard carotid artery ultrasound examinations were performed in 51 patients with carotid artery plaques before carotid endarterectomy. Hematoxylin-eosin staining and Sirius red-picric acid staining of plaque sections were performed to analyze the pathological features and collagen distribution. All plaques were classified into vulnerable and stable groups by pathological features. Ultrasound scores, cap thickness, and the ratios of different collagen types were recorded and analyzed between two groups and different parts of plaques. Results: Ultrasound scores of the vulnerable group were higher than those of the stable group (4.35 ± 1.23 vs. 2.09 ± 1.04, P = 0.001). AUC was 0.894 (best cutoff point three) in differentiating vulnerable and stable plaques. Compared with the stable group, the fibrous caps of the vulnerable group were thinner (P = 0.012); the area ratios of collagen type I to all collagen in the vulnerable group were lower (P = 0.033); however, the area ratios of collagen type IV to all collagen were higher (P = 0.026). Compared with downstream shoulders, the ultrasound scores of upstream shoulders of plaque were higher (P = 0.001), the fibrous caps of upstream shoulders were thinner (P = 0.001), and the area ratios of collagen type I to all collagen were lower (P = 0.022). Conclusion: Ultrasound score could have a clinical value in identifying vulnerable carotid artery plaque, and the collagen distribution could impact the stability of plaques, especially collagen type I and type IV. The results also prompted that the upstream shoulders were more vulnerable than the downstream shoulders.

Evaluation of Revascularization in Different Suzuki Stages of Ischemic Moyamoya Disease by Whole-Brain CT Perfusion.

Objective: This study compared the clinical features and hemodynamic characteristics of patients in different Suzuki stages of ischemic moyamoya disease (iMMD) before and after treatment with extracranial-intracranial (EC-IC) bypass surgery combined with encephalo-duro-myo-synangiosis and whole-brain computed tomography perfusion (WB-CTP). Methods: A total of 126 patients in different Suzuki stages (II, III, IV, and V) of iMMD who underwent bypass surgery from April 2013 to August 2020 were included in this retrospective study. MIStar automatic analysis of Whole brain CT perfusion imaging software (WB-CTP, Apollo Medical Imaging Technology, Melbourne, Australia) was used. The patients also underwent WB-CTP 1 day before and 1 week and 3 months after the surgery. The relationships between hemodynamic parameters in WB-CTP including delay time (DT) > 3 s, relative cerebral blood flow (rCBF) < 30%, mismatch and mismatch ratio, and clinical outcomes were evaluated for different Suzuki stages, with comparisons between early (II and III) and late (IV and V) stages. Results: Combined bypass surgery was performed in 161 hemispheres of 126 patients with iMMD. Brain volume with DT > 3 s was decreased 1 week (51.5 ± 11.8 ml, P < 0.05) and 3 months (41.5 ± 10.7 ml, P < 0.05) after bypass compared to 1 day before bypass (104.7 ± 15.1 ml) in early-stage patients. In late-stage patients, the volume was increased 1 week after bypass compared to the preoperative value (154.3 ± 14.7 vs. 118.3 ± 19.1 ml, P < 0.05). Preoperative brain volume with rCBF < 30% was lower (9.8 ± 3.9 vs. 33.5 ± 11.0 ml) whereas preoperative mismatch ratio was higher (11.2 ± 2.8 vs. 3.6 ± 1.6) in early-stage as compared to late-stage patients (both P < 0.05). A higher modified Rankin scale score (0-1) was achieved by early-stage patients than by those in the late stage (93.8 vs. 80.4%, P < 0.05) at the 3-month follow-up. Conclusions: WB-CTP is useful for assessing the effectiveness of combined bypass/revascularization in different Suzuki stages of iMMD. Patients in the early stage of disease with higher preoperative brain volume with DT > 3 s and mismatch ratio show greater improvements in hemodynamic parameters and fewer postoperative complications associated with hemodynamic disturbance following bypass than patients in the late stage. Preoperative mismatch ratio can serve as a marker for assessing the status of collateral circulation in different Suzuki stages of iMMD.

Cerebral revascularization for the management of complex middle cerebral artery aneurysm: A case series.

Complex middle cerebral artery (MCA) aneurysms, including aneurysms that are sizeable (large or giant), fusiform, wide-necked or calcified, remain a significant challenge during microsurgical clipping or endovascular coiling as treatment strategies. In the present study, a retrospective analysis of cases of this type of aneurysm treated between August 2012 and December 2019 was performed. From the hospital's database, a total of 13 patients (7 males and 6 females) with a mean age of 39.0 years (range, 13-65 years) were identified. The mean size of the aneurysms was 17.5 mm (range, 3.9-35.0 mm). A total of four patients (30.8%) had ruptured aneurysms and nine (69.2%) had unruptured aneurysms. All aneurysms were treated by proximal occlusion of the parent artery, trapping or excision combined with cerebral revascularization. The bypasses performed included 10 extracranial-intracranial bypasses and 3 intracranial-intracranial bypasses (1 end-to-end re-anastomosis, 1 interpositional graft and 1 end-to-side reimplantation). Postoperative angiography confirmed that the bypass patency was 92.3% and the clinical outcomes were indicated to be favorable, with a modified Rankin Scale score ≤2 in 12 out of 13 patients (92.3%) at the last follow-up. Taken together, the results of the present analysis suggested that treatment strategies for complex MCA aneurysms should depend on the status and characteristics of the aneurysm, including aneurysm size, location and morphology. For aneurysms that lack perforating arteries in the aneurysm dome, clip trapping or aneurysm excision with or without bypass are preferred as treatment strategies. When there are perforating arteries (particularly the lenticulostriate artery) arising from the aneurysm dome, however, the aneurysms should be treated with bypass followed by proximal occlusion of the parent artery or clip reconstruction.

Cerebral Revascularization for the Management of Symptomatic Pure Arterial Malformations.

Background: Pure arterial malformations (PAMs) are extremely rare abnormalities defined as dilated, overlapping, and tortuous arteries with a coil-like appearance in the absence of venous components. Over the last half century, only seven published reports have described cases of patients with PAMs who received treatment. Methods: Here, we report two cases of women with PAMs who received surgical treatment, and we present a systematic review of the literature. We searched the PubMed, Embase, Web of Science, and Medline databases (up until October 1, 2021) for relevant publications. We performed independent-sample t-tests and Fisher's exact tests to compare continuous and categorical characteristics among the available cases. Results: Our first patient was a 43-year-old woman with PAM of the left internal carotid artery (ICA), who received an ICA-radial artery (RA)-M2 bypass. Post-operative digital subtraction angiography (DSA) revealed the disappearance of the left ICA PAM without ischemic events during follow-up. The second patient was a 53-year-old woman with PAMs of the right ICA and posterior cerebral artery. The P1 lesion was treated by proximal occlusion combined with a superficial temporal artery-P2 bypass. During the 12-month follow-up period, the size of the PAMs decreased significantly as indicated by the post-operative DSA showing the absence of hemorrhages. Our systematic review, which includes 56 PAMs, shows that the reported PAMs were more common in the anterior circulation (33/56, 58.9%) than in the posterior circulation (11/56, 19.7%). Bilateral PAMs were more likely to affect bilateral anterior cerebral arteries (ACA) (ACAbilateral vs. ACAunilateral: 63.6 vs. 26.2%, p = 0.02). In addition, PAMs involving the anterior circulation were likely to affect multiple arteries (anteriormulti vs. posteriormulti: 30.3 vs. 0%, p = 0.038). Conclusion: We found very few reports on treated PAMs; further studies with large sample sizes and long follow-up periods are required to explore the appropriate treatment strategy for PAMs.

Assessment of Transient Cerebral Hemodynamic Disturbance via Whole-Brain Computed Tomography Perfusion After Extracranial-Intracranial Bypass in Ischemic Moyamoya Disease.

OBJECTIVE: To assess the cerebral hemodynamic data associated with transient cerebral hemodynamic disturbance (TCHD), including cerebral hyperperfusion syndrome (CHS) and watershed shift ischemia (WSI), by whole-brain (WB) computed tomography perfusion (CTP) before and after revascularization for ischemic moyamoya disease. METHODS: A total of 115 consecutive patients with ischemic moyamoya disease underwent revascularization. All patients underwent WB-CTP 24 hours before operation and on the day of onset of TCHD and 6 months after revascularization. The volumes of delay time (DT) >3 seconds and mismatch and relative cerebral blood flow <30% were calculated in 3 time points. RESULTS: Of the 115 patients, 18 115 had TCHD, comprising 10 with CHS and 8 with WSI. Compared with the brain volume of DT >3 seconds before revascularization, the volume decreased significantly (P < 0.05) on the day of CHS. The volume of mismatch in 3 time points indicated no significant differences (P > 0.05). The volume of relative cerebral blood flow <30% showed obvious differences of significance among 10 patients with CHS (P < 0.05) at 3 time points. In the WSI group, the volume of DT >3 seconds, mismatch, and DT >3 seconds showed significant differences, relatively (P < 0.05), at 3 time points. At the time of onset of TCHD, DT >3 seconds and mismatch in the CHS group were dramatically lower than those in the WSI group (P < 0.05). DT >3 seconds in the no-TCHD group showed significant differences (P < 0.05) at 3 time points. CONCLUSIONS: WB-CTP could be used to assess the cerebral hemodynamic characteristics before and after revascularization. DT >3 seconds and mismatch played important roles in evaluating distinct features of TCHD.

Evaluation of Carotid Plaque Rupture and Neovascularization by Contrast-Enhanced Ultrasound Imaging: an Exploratory Study Based on Histopathology.

A significant portion of ischemic stroke is on account of emboli caused by fibrous cap rupture of vulnerable plaque with intraplaque neovascularization as a significant triggering factor to plaque vulnerability. Contrast-enhanced ultrasound (CEUS) could offer detailed information on plaque surface and intraplaque microvascular. This study aims to comprehensively assess the value of CEUS for the detection of plaque rupture and neovascularization in histologically verified plaques that had been removed from the patients who had undergone carotid endarterectomy (CEA). Fifty-one consecutive subjects (mean age, 67.0 ± 6.5 years; 43 [84.3%] men) scheduled for CEA were recruited. Standard ultrasound and CEUS were performed prior to surgery. Based on the direction of the contrast agents that diffuse within the plaques, plaques were divided as "inside-out" direction (contrast agents diffuse from the artery lumen towards the inside of the plaque) and non-inside-out direction. Plaque enhancement was assessed by using a semi-quantitative grading scale (grade 1: no enhancement; grade 2: moderate enhancement; grade 3: extensive enhancement). Plaques were evaluated for histopathologic characteristics according to Oxford Plaque Study (OPS) standard postoperative. Intraplaque neovascularization as manifested by the appearance of CD34-positive microvessels was characterized in terms of microvessel density (MVD), microvessel area (MVA), and microvessel shape (MVS). In 51 plaques, the sensitivity, specificity, positive, and negative predictive values of contrast agent inside-out direction diffusion for the detection of plaque fibrous cap rupture were 87.5%, 92.6%, 91.3%, and 89.3%, respectively. The incidence of cap rupture was significantly higher in contrast agent inside-out direction diffusion than non-inside-out direction diffusion (73.9% vs 25.0%, p < 0.001), and inside-out direction diffusion did exhibit higher frequency of vulnerable plaques (OPS grades 3-4) (95.7% vs 53.6%, p = 0.001). Multivariate logistic regression analysis revealed the contrast agent inside-out direction diffusion as an independent correlate to plaque rupture (OR 8.5, 95% CI 2.4-30.1, p = 0.001). With increasing plaque enhancement, plaque MVD (p < 0.001), plaque MVA (p = 0.012), and percentage of highly irregular-shaped microvessels increased (p < 0.001). Contrast agent inside-out direction diffusion could indicate plaque rupture. The increase in plaque enhancement paralleled increased, larger, and more irregular-shaped microvessels, which may suggest an increased risk of plaque vulnerability.

Decreased cortical perfusion in areas with blood-brain barrier dysfunction in Moyamoya disease.

BACKGROUND: Recently, several studies have focused on the relationship between blood-brain barrier (BBB) impairment and the etiology of Moyamoya disease (MMD). However, in vivo studies investigating about BBB impairment and cortical perfusion in MMD patients were really rare. METHODS: This study included 16 patients diagnosed with MMD and 9 patients with atherosclerotic cerebrovascular disease (ACVD); all of who were treated with superficial temporal artery-middle cerebral artery (STA-MCA) bypass. Cortical perfusion was assessed using intraoperative indocyanine green (ICG) videoangiography by calculating the blood flow index (BFI). In addition, we used sodium fluorescein (NaFl) to evaluate the permeability of BBB in vivo during operation. RESULTS: The results showed that BBB impairment in MMD patients was more significant than that in ACVD patients, whereas, the cortical perfusion was comparable between two groups. BFI was significantly improved after STA-MCA bypass both in the MMD group (post-operation vs pre-operation: 109.2 ± 67.7 vs 64.3 ± 35.0, p = 0.004) and the ACVD group (post-operation vs pre-operation: 137.6 ± 89.6 vs 90.8 ± 58.3, p = 0.015). Moreover, BFI was significantly decreased in the cortex with BBB impairment as compared with that in the cortex with intact BBB (impaired BBB vs intact BBB: 55.7 ± 26.5 vs 87.6 ± 55.1, p = 0.025). Following bypass, the cortical perfusion significantly improved in the area of BBB impairment (post-operation vs pre-operation: 93.8 ± 75.2 vs 55.7 ± 26.5, p = 0.004), which was not observed in the BBB intact area (post-operation vs pre-operation: 92.4 ± 50.4 vs 87.6 ± 55.1, p = 0.58). CONCLUSION: In summary, we observed that BBB impairment in MMD patients was more significant than that in ACVD patients. This study also demonstrated for the first time that cortical perfusion was significantly decreased in the cortex with BBB impairment as compared with that in the cortex with intact BBB in MMD patients. We also observed that After STA-MCA bypass, the cortical perfusion was significantly improved in the cortex with BBB impairment. These results may provide a new insight for BBB impairment and cortical perfusion in the etiology of MMD.

Quantitative analysis of revascularization in ischemic moyamoya disease via whole-brain computed tomography perfusion: A retrospective single-center study.

Ischemic moyamoya disease (MMD) can be treated with the revascularization of superficial temporal artery to middle cerebral artery (STA-MCA) bypass combined with encephalo-duro-arterio-myo-synangiosis (EDAMS) effectively. The purpose of the present study was to quantify the revascularization of STA-MCA bypass combined with EDAMS via whole-brain computed tomography perfusion (WB-CTP).Seventy-nine consecutive patients with ischemic MMD who admitted to our hospital from August 2012 to October 2018 were carried out STA-MCA bypass combined with EDAMS. WB-CTP was performed at 24 hours prior to operation and 3 months following bypass with a follow-up WB-CTP, respectively. Both automatic analysis of WB-CTP (MIStar, Apollo Medical imaging Technology, Melbourne, Australia) for analyzing values of brain volume in delayed time (DT) >3 seconds and DT > 6 seconds, relative cerebral blood flow (γCBF) < 30% and its mismatch ratio or percentage and diffusion-weighted imaging of magnetic resonance imaging in the ischemic penumbra and the infarct core at the 2 time points were studied for verifying the effectiveness of the combined revascularization. Changes in DT values at MCA-terminal territory after revascularization had been investigated. The dynamic data were with reference to the individual cerebellar arteries.All patients with ischemic MMD underwent STA-MCA bypass combined with EDAMS successfully. The preoperative brain volume in DT > 3 seconds in MCA-terminal territory was significantly larger than that of postoperative one (P < .05) in the ischemic penumbra in ischemic MMD. The mismatch ratio in brain volume of 24 hours prior to revascularization in MCA-terminal territory was significantly lower than that of 3 months (P < .05) following combined revascularization. The percentage of mismatch in brain volume of 24 hours prior to revascularization vs that of 3 months and the value of γCBF < 30% were similar to the above mismatch ratio (P < .05). The ratio of postoperative brain volume in DT > 3 seconds vs DT > 6 seconds indicated no significant differences compared with that of preoperative one (P > .05).The WB-CTP can be regarded as a choice for quantifying the combined revascularization in the ischemic penumbra and the infarct core in ischemic MMD. As proposed methods, brain volume in DT > 3 seconds, the value of γCBF < 30% and mismatch ratio in brain volume in MCA-terminal territory should be paid more attention in assessing the validity of STA-MCA bypass combined with EDAMS in ischemic MMD.

Surgical Revascularization: Ligation of Extracranial Internal Carotid Artery and Superficial Temporal Artery-to-Middle Cerebral Artery Bypass in Patient with Extracranial Internal Carotid Aneurysm and Hemorrhagic Moyamoya Disease.

BACKGROUND: Extracranial internal carotid artery (EICA) aneurysm is regarded as a rare lesion. What is more, patients can suffer from EICA aneurysms and hemorrhagic moyamoya disease (MMD) simultaneously. CASE DESCRIPTION: A 38-year-old man was admitted to our hospital and underwent emergent tracheal intubation for hoarseness and breathing difficulty for 1 day. He had a pulsating mass of 2.5 cm in diameter in the left cervical area. Imaging examinations revealed the left EICA aneurysm and MMD. The patient underwent left superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass and ligation of the left EICA simultaneously. Computed tomography revealed hemorrhagic stroke in the right basal ganglia region 20 days after the bypass. The hematoma disappeared 20 days after the stroke. Right bypass was performed 6 months after the left bypass. The patient was discharged with no neurologic abnormalities 10 days after the right bypass. He lived a normal life, and no neurologic abnormalities were found at the 6-month follow-up. Imaging examinations indicated the efficacy of the bilateral STA-MCA bypass and verified the disappearance of the left EICA aneurysm after the ligation. CONCLUSIONS: We present a case of EICA aneurysm and hemorrhagic MMD. Ligation of the left ECA eliminates the EICA aneurysm with no neurologic abnormalities. STA-MCA bypass can be regarded as an effective choice for hemorrhagic MMD. Further studies should be performed to confirm the effectiveness of combined surgical revascularization.

Cotton-Assisted Surgical Clipping of Very Small Aneurysms: A Two-Center Study.

OBJECTIVE: Very small intracranial aneurysms (VSIAs) are challenging to treat because aneurysm tearing and clip slippage can occur during neurosurgical clipping. In this study, we introduce and share our experience with cotton-assisted clipping of VSIAs. METHODS: We retrospectively analyzed the data of 20 patients with 24 VSIAs treated with cotton-assisted clipping between February 2008 and December 2014 in the Neurosurgery Departments of the First Affiliated Hospital, Soochow University and Taizhou People's Hospital. During surgery, 2 aneurysm necks were torn. To treat the tears, we wrapped rectangular cotton pads around the parental arteries at the site of rupture. The remaining 22 aneurysms were clipped after being wrapped in cotton pads. RESULTS: The 2 aneurysm ruptures were successfully repaired with cotton-assisted clipping. In the remaining 22 aneurysms, no cases of aneurysm clip slippage or aneurysm rupture occurred. Patients were followed up on average for 59.0 months (range, 30-113 months). Of the 20 patients, the 16 patients with preoperative Hunt-Hess grades of 1-3 recovered well after the surgery (Glasgow Outcome Scale [GOS] score, 5). Of the 4 patients with Hunt-Hess grades of 4-5, 3 had a good recovery (GOS scores, 4-5), and 1 patient died of heart disease 6 months after being discharged from the hospital; this patient had a GOS score of 4 at the time of discharge. CONCLUSIONS: Cotton-assisted clipping could prevent aneurysm clip slipping and aneurysm rupture and facilitate the repair of aneurysm neck tears. This technique is a useful alternative therapy for VSIAs.

Superficial and multiple calcifications and ulceration associate with intraplaque hemorrhage in the carotid atherosclerotic plaque.

OBJECTIVE: Intraplaque hemorrhage (IPH) and ulceration of carotid atherosclerotic plaques have been associated with vulnerability while calcification has been conventionally thought protective. However, studies suggested calcification size and location may increase plaque vulnerability. This study explored the association between calcium configurations and ulceration with IPH. METHODS: One hundred thirty-seven consecutive symptomatic patients scheduled for carotid endarterectomy were recruited. CTA and CTP were performed prior to surgery. Plaque samples were collected for histology. According to the location, calcifications were categorized into superficial, deep and mixed types; according to the size and number, calcifications were classified as thick and thin, multiple and single. RESULTS: Seventy-one plaques had IPH (51.8%) and 83 had ulceration (60.6%). The appearance of IPH and ulceration was correlated (r = 0.49; p < 0.001). The incidence of multiple, superficial and thin calcifications was significantly higher in lesions with IPH and ulceration compared with those without. After adjusting factors including age, stenosis and ulceration, the presence of calcification [OR (95% CI), 3.0 (1.1-8.2), p = 0.035], multiple calcification [3.9 (1.4-10.9), p = 0.009] and superficial calcification [3.4 (1.1-10.8), p = 0.001] were all associated with IPH. ROC analysis showed that the AUC of superficial and multiple calcifications in detecting IPH was 0.63 and 0.66, respectively (p < 0.05). When the ulceration was combined, AUC increased significantly to 0.82 and 0.83, respectively. Results also showed that patients with lesions of both ulceration and IPH have significantly reduced brain perfusion in the area ipsilateral to the infarction. CONCLUSIONS: Superficial and multiple calcifications and ulceration were associated with carotid IPH, and they may be a surrogate for higher risk lesions. KEY POINTS: • CTA-defined superficial and multiple calcifications in carotid atherosclerotic plaques are independently associated with the presence of intraplaque hemorrhage. • The combination of superficial and multiple calcifications and ulceration is highly predictive of carotid intraplaque hemorrhage. • Patients with lesions of both ulceration and intraplaque hemorrhage have significantly reduced brain perfusion in the area ipsilateral to the infarction.

Extracranial-intracranial bypass in medial sphenoid ridge meningioma associated with severe stenosis of the intracranial segments of the internal carotid artery: A case report.

RATIONALE: Tumor resection and extracranial-intracranial bypass concerning medial sphenoid ridge meningioma associated with severe stenosis of the internal carotid artery (ICA) of intracranial segments has been rarely presented. Effective treatment as to the complex lesions may be complicated. Tumor resection and cerebrovascular protection should be both taken into consideration. PATIENT CONCERNS: We presented one case of medial sphenoid ridge meningioma associated with severe stenosis of the internal carotid artery of intracranial segments. The patient suffered hyperthyroidism, mirror-image dextrocardia and congenital heart disease atrial septal defect simultaneously. DIAGNOSES: Before the neurosurgical treatment , the colleagues of department of cardiac surgery, anesthesiology and respiratory medicine agreed on our plan of resecting the tumor following the comprehensive evaluation of basal clinical conditions in the patient. For reducing the bleeding intraoperatively, the interventional branch performed digital subtraction angiography(DSA) and found collateral anastomosis between the supplying vessels of left middle meningeal arteries and anterior choroid arteries. No preoperative interventional embolization was determined considering the risk of cerebral ischemia. INTERVENTIONS: The following subtotal resection of medial sphenoid ridge meningioma and left extracranial-intracranial bypass were carried out. Additionally, ipsilateral decompressive craniectomy was done. Post-operative imaging Computed tomography (CT), Computed tomography angiography (CTA) and Transcranial Doppler (TCD) indicated subtotal resection of tumor and bypass patency. OUTCOMES: The patient was discharged with the right limbs of muscle strength of grade IV. The muscle strength of the patient returned to grade V after 6 months of follow-up. LESSONS: Comprehensive treatment of tumor resection and extracranial-intracranial bypass concerning medial sphenoid ridge meningioma associated with severe stenosis of the internal carotid artery of intracranial segments is effective.