Symptomatic Cerebrovascular Disease Research Articles

Increased Risk of Recurrent Stroke in Symptomatic Large Vessel Disease With Impaired BOLD Cerebrovascular Reactivity.

Impaired cerebrovascular reactivity (CVR) has been correlated with recurrent ischemic stroke. However, for clinical purposes, most CVR techniques are rather complex, time-consuming, and lack validation for quantitative measurements. The recent adaptation of a standardized hypercapnic stimulus in combination with a blood-oxygenation-level-dependent (BOLD) magnetic resonance imaging signal as a surrogate for cerebral blood flow offers a potential universally comparable CVR assessment. We investigated the association between impaired BOLD-CVR and risk for recurrent ischemic events. We conducted a retrospective analysis of patients with symptomatic cerebrovascular large vessel disease who had undergone a prospective hypercapnic-challenged BOLD-CVR protocol at a single tertiary stroke referral center between June 2014 and April 2020. These patients were followed up for recurrent acute ischemic events for up to 3 years. BOLD-CVR (%BOLD signal change per mm Hg CO2) was calculated on a voxel-by-voxel basis. Impaired BOLD-CVR of the affected (ipsilateral to the vascular pathology) hemisphere was defined as an average BOLD-CVR, falling 2 SD below the mean BOLD-CVR of the right hemisphere in a healthy age-matched reference cohort (n=20). Using a multivariate Cox proportional hazards model, the association between impaired BOLD-CVR and ischemic stroke recurrence was assessed and Kaplan-Meier survival curves to visualize the acute ischemic stroke event rate. Of 130 eligible patients, 28 experienced recurrent strokes (median, 85 days, interquartile range, 5-166 days). Risk factors associated with an increased recurrent stroke rate included impaired BOLD-CVR, a history of atrial fibrillation, and heart insufficiency. After adjusting for sex, age group, and atrial fibrillation, impaired BOLD-CVR exhibited a hazard ratio of 10.73 (95% CI, 4.14-27.81; P<0.001) for recurrent ischemic stroke. Among patients with symptomatic cerebrovascular large vessel disease, those exhibiting impaired BOLD-CVR in the affected hemisphere had a 10.7-fold higher risk of recurrent ischemic stroke events compared with individuals with nonimpaired BOLD-CVR.

About chronic cerebrovascular insufficiency caused by cardiac pathology (literature review)

The widespread introduction of cardiological diagnostic methods in clinical angioneurology has significantly enriched the data on the role of cardiovascular diseases in the development of cerebrovascular pathology. Various cardiac disorders play a significant role in the development of cardioembolic and haemodynamic ischaemic strokes. It has been scientifically proven that chronic heart failure, along with hypertension, is a risk factor for the occurrence of a chronic form of cerebrovascular disease — chronic cerebrovascular insufficiency. The characteristic feature of all types of cardiovascular insufficiency is the inability of the circulatory system to deliver to the organs, systems, tissues, including the brain, the amount of blood necessary for their normal functioning, both at rest and especially during exertion. In their daily practice, neurologists encounter patients with chronic heart failure and symptoms of cerebrovascular disease (memory loss, reduced performance, depression). Underestimation of these conditions can result in a shortened life due to irreversible damage to target organs (heart, brain, kidneys). In the absence of adequate treatment, death is possible within the first 5 years after the onset of heart failure. The degree of disease progression depends on many factors: clinical and pathogenetic variant of chronic heart failure, the rate of the pathological process, the presence of myocardial damage and remodeling, complications from target organs. In this article, we tried to analyse the literature data of domestic and foreign authors on the pathogenetic mechanisms of chronic heart failure, the impact on its development and the course of its complications, and, above all, brain damage in the form of chronic cerebrovascular insufficiency.

New evidence for fractional pressure ratio prediction by pulsatility index from transcranial Doppler in patients with symptomatic cerebrovascular stenosis disease.

The pulsatility index (PI) derived from transcranial Doppler (TCD) assessment may represent the cerebral resistance and altered cerebral blood flow. The purpose of this study was to assess the performance of the TCD PI in correlation with wire-based fractional pressure ratio (FPR). This study included 33 patients with symptomatic atherosclerotic lesions of the extracranial and intracranial large arteries, specifically the internal carotid artery, middle cerebral artery (MCA), vertebral artery (VA) V4 segment, and basilar artery (BA), all of which exhibited luminal stenosis ranging from 50% to 70%. TCD was performed prior to angiography in order to determine the flow distal to the lesion. We performed cerebrovascular angiography with a pressure wire to measure the FPR of vessels with stenotic lesions. Bland-Altman analysis and ordinal least square (OLS) linear regression were used to quantify the correlation between PI and FPR. A total of 42 TCD data points were analyzed. At the TCD locations distal to the lesions, the correlation coefficients were no less than 0.90%, with almost all P values <0.001, which indicated very strong positive correlations; the exception to this was the distal TCD for MCA segment lesions (r=0.897; P=0.015) and VA V4 segment (r=0.964; P=0.036). The Bland-Altman plot demonstrated a small difference (0.003) between the distal TCD PI and the FPR, with an acceptable 95% confidence interval [95% confidence interval (CI): 0.06-0.12]. The PI obtained through TCD assessment distal to the stenotic lesion exhibited a correlation with the FPR computed using pressure wire measurements.

Hemodynamic Failure Staging With Blood Oxygenation Level-Dependent Cerebrovascular Reactivity and Acetazolamide-Challenged (15O-)H2O-Positron Emission Tomography Across Individual Cerebrovascular Territories.

Staging of hemodynamic failure (HF) in symptomatic patients with cerebrovascular steno-occlusive disease is required to assess the risk of ischemic stroke. Since the gold standard positron emission tomography-based perfusion reserve is unsuitable as a routine clinical imaging tool, blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR) with CO2 is a promising surrogate imaging approach. We investigated the accuracy of standardized BOLD-CVR to classify the extent of HF. Patients with symptomatic unilateral cerebrovascular steno-occlusive disease, who underwent both an acetazolamide challenge (15O-)H2O-positron emission tomography and BOLD-CVR examination, were included. HF staging of vascular territories was assessed using qualitative inspection of the positron emission tomography perfusion reserve images. The optimum BOLD-CVR cutoff points between HF stages 0-1-2 were determined by comparing the quantitative BOLD-CVR data to the qualitative (15O-)H2O-positron emission tomography classification using the 3-dimensional accuracy index to the randomly assigned training and test data sets with the following determination of a single cutoff for clinical application. In the 2-case scenario, classifying data points as HF 0 or 1-2 and HF 0-1 or 2, BOLD-CVR showed an accuracy of >0.7 for all vascular territories for HF 1 and HF 2 cutoff points. In particular, the middle cerebral artery territory had an accuracy of 0.79 for HF 1 and 0.83 for HF 2, whereas the anterior cerebral artery had an accuracy of 0.78 for HF 1 and 0.82 for HF 2. Standardized and clinically accessible BOLD-CVR examinations harbor sufficient data to provide specific cerebrovascular reactivity cutoff points for HF staging across individual vascular territories in symptomatic patients with unilateral cerebrovascular steno-occlusive disease.

LIGHT/TNFSF14 levels in carotid atherosclerotic plaques are associated with symptomatic cerebrovascular disease

Abstract Background Plaque rupture is the underlying cause of most cardiovascular events, such as stroke and myocardial infarction. Co-stimulatory molecules, the immune checkpoints, are emerging as strong candidates to battle atherosclerosis progression. The co-stimulatory molecule LIGHT (tumour necrosis factor 14; TNFSF14) exists in foam cell-rich regions of atherosclerotic plaques, but whether it has a driving role in promoting a high-risk plaque phenotype is not known. Purpose This study investigates the association between intra-plaque LIGHT and plaque vulnerability. Methods Plaque levels of LIGHT/TNFSF14 were measured in homogenised carotid endarterectomy plaques by Proximity Extension Assay (PEA) in subjects from the Carotid Plaque Imaging Cohort (CPIP; N=201). Homogenates were further examined by multi-plex cytokine analysis and ELISA, and tissue plaque sections through histology/immunohistochemistry. Results Plaque levels of LIGHT were associated with the occurrence of pre-operative cerebrovascular symptoms (p=0.00014). Furthermore, LIGHT correlated strongly with the histological plaque vulnerability index (p=5x10-15): a ratio between the sum of destabilising versus stabilising plaque components (i.e. macrophages, intra-plaque haemorrhage and lipids versus smooth muscle cells and collagen) as well as with necrotic core size and the inflammatory cytokines interleukin(IL)-1β, IL-6, chemokine (C-C motif) ligand (CCL)-2, CCL4 and CCL5. Moreover, plaque LIGHT levels correlated with several components of the extracellular matrix turnover machinery, including cleaved collagen, the collagen cross-linking proteoglycans fibromodulin and lumican, the matricellular protein COMP (cartilage oligomeric matrix protein), and the remodelling regulator ADAMTS7 (a disintegrin and metalloproteinase with thrombospondin motifs-7). Levels also correlated with matrix metalloproteinases (MMPs) 1, 2, 9 and 10, and tissue inhibitor of metalloproteinase (TIMP)-1. Conclusion Expression of LIGHT in atherosclerotic plaques does not only correlate with markers of plaque destabilisation¸ but is also significantly elevated in plaques from symptomatic, compared to asymptomatic, patients. These results connect LIGHT content to a rupture-prone plaque phenotype and suggest the LIGHT signalling pathway as a potential therapeutic target to promote atherosclerotic plaque stability.

Ischemic stroke recurrence and mortality in different imaging phenotypes of ischemic cerebrovascular disease: The SMART-MR Study.

Diagnosis of cerebrovascular disease is based on both clinical and radiological findings, however, they do not always correlate. To investigate ischemic stroke recurrence and mortality in patients with different imaging phenotypes of ischemic cerebrovascular disease. Within the SMART-MR study, a prospective patient cohort with arterial disease, cerebrovascular diseases of participants at baseline were classified as no cerebrovascular disease (reference group, n = 828), symptomatic cerebrovascular disease (n = 204), covert vascular lesions (n = 156), or imaging negative ischemia (n = 90) based upon clinical and MRI findings. Ischemic strokes and deaths were collected at 6 month-intervals up to 17 years of follow-up. With Cox regression, relationships between phenotype and ischemic stroke recurrence, cardiovascular mortality, and non-vascular mortality were studied adjusted for age, sex, and cardiovascular risk factors. Compared to reference group risk for recurrent ischemic stroke was increased not only in the symptomatic cerebrovascular disease (HR 3.9, 95% CI 2.3-6.6), but also in the covert vascular lesion (HR 2.5, 95% CI 1.3-4.8) and the imaging negative ischemia groups (HR 2.4, 95% CI 1.1-5.5). Risk for cardiovascular mortality was increased in the symptomatic cerebrovascular disease (HR 2.2, 95% CI 1.5-3.2) and covert vascular lesions groups (HR 2.3, 95% CI 1.5-3.4), while the risk was less strong but also increased in the imaging negative ischemia group (HR 1.7, 95% CI 0.9-3.0). People with all imaging phenotypes of cerebrovascular disease have increased risk of recurrent ischemic stroke and mortality compared to other arterial diseases. Strict preventive measures should be performed even when imaging findings or clinical symptoms are absent. For use of anonymized data, a reasonable request has to be made in writing to the UCC-SMART study group and the third party has to sign a confidentiality agreement.

Pituitary adenomas and cerebrovascular disease: A review on pathophysiology, prevalence, and treatment.

Pituitary adenomas (PAs) have been shown to cause excess cardiovascular disease comorbidity and mortality. Cerebrovascular disease (CeVD) is a small subset of cardiovascular disease with high morbidity, and its risk in patients with pituitary adenomas has been sparingly explored. In this review, we examine what is known about the prevalence of cerebrovascular disease in patients with PAs, from its initial discovery in 1970 to present. An abundance of literature describes increased cerebrovascular mortality in patients with acromegaly, while research on other PA subtypes is less frequent but shows a similarly elevated CeVD mortality relative to healthy populations. We also review how cerebrovascular risk changes after PAs are treated, with PA treatment appearing to prevent further accumulation of cerebrovascular risk without reversing prior elevations. While acromegaly-associated CeVD appears to becaused by elevated growth hormone (GH) levels and Cushing disease's elevated glucocorticoids similarly cause durable alterations in cerebrovascular structure and function, less is known about the mechanisms behind CeVD in other PA subpopulations. Proposed pathophysiologies include growth hormone deficiency inducing vessel wall damage or other hormone deficits causing increased atherosclerotic disease. Early diagnosis and treatment of PAs may be the key to minimizing lifetime CeVD risk elevations. More research is needed to better understand the mechanisms behind the increased CeVD seen in patients with PAs. Physicians caring for PA patients must remain vigilant for signs and symptoms of cerebrovascular disease in this patient population.

Crossed cerebellar diaschisis-related supratentorial hemodynamic and metabolic status measured by PET/MR in assessing postoperative prognosis in chronic ischemic cerebrovascular disease patients with bypass surgery

ObjectiveCerebral ischemic status is an indicator of bypass surgery. Both hemodynamics and glucose metabolism are significant factors for evaluating cerebral ischemic status. The occurrence of crossed cerebellar diaschisis (CCD) is influenced by the degree of supra-tentorial perfusion and glucose metabolism reduction. This study aimed to investigate the relationship between the CCD-related supra-tentorial blood flow and metabolic status before bypass surgery in patients with chronic and symptomatic ischemic cerebrovascular disease and the prognosis of surgery.MethodsTwenty-four participants with chronic ischemic cerebrovascular disease who underwent hybrid positron emission tomography (PET)/magnetic resonance (MR) before bypass surgery were included. Arterial spin labeling (ASL)-MR and FDG-PET were used to measure blood flow and metabolism, respectively. The PET images were able to distinguish CCD. The supratentorial asymmetry index (AI) and volume in the decreased blood flow region, decreased metabolism region and co-decreased region on the affected side, except for the infarct area, were respectively obtained before bypass surgery. The neurological status was determined using the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores. Differences between CCD-positive (CCD +) and CCD-negative (CCD−) groups were investigated.ResultsFourteen (58%) of the 24 patients were diagnosed as CCD +. Before surgery, the NIHSS and mRS scores of the CCD + were significantly higher than those of the CCD− (1.0(1.0) vs. 0.0(1.0), P = 0.013; 1.0(1.5) vs. 0.0(1.5), P = 0.048). After the surgery, the NIHSS and mRS scores of the CCD + showed a significant decrease (0.0(1.0) to 0.0(0.0), P = 0.011; 0.0(0.5) to 0.0(0.0), P = 0.008). Significant differences were observed in the supra-tentorial decreased metabolism region (all Ps ≤ 0.05) between the CCD + and CCD− groups, but no differences were observed in the preprocedural decreased supratentorial blood flow region (P > 0.05). The preprocedural NIHSS score was strongly correlated with the metabolism AI value in the decreased metabolism region (r = 0.621, P = 0.001) and the co-decreased region (r = 0.571, P = 0.004).ConclusionsSupratentorial blood flow and metabolism are important indicators of CCD. This study showed that CCD + patients benefited more from bypass surgery than CCD− patients. Staging based on CCD-related supra-tentorial blood flow and metabolic status by hybrid PET/MR may help to personalize treatment.

The Prognostic Role of ST2L and sST2 in Patients Who Underwent Carotid Plaque Endarterectomy: A Five-Year Follow-Up Study.

Soluble suppressor of tumorigenicity (sST)-2 plasma concentration is related to atherosclerosis. The aim of this study was to assess the prognostic impact of sST2 and its membrane-associated form (ST2L) in patients with carotid atherosclerotic plaque who underwent endarterectomy (CEA). Eighty-two consecutive patients (age range: 48–86 years) who underwent CEA were enrolled. Anthropometric, clinical, instrumental, and laboratory evaluations were gathered. Thirty-seven (45%) patients were symptomatic of cerebrovascular diseases. Patients underwent a five-year follow-up. Phone calls and the analysis of national and regional databases were performed in order to evaluate the occurrence of the primary outcome (all-cause mortality). The population was divided according to survival status. Statins were administered in 81% and 87.5% of survivors and non-survivors, respectively. sST2 levels were higher in non-survivors than in survivors (117.0 ± 103.9 vs. 38.0 ± 30.0 ng/mL, p < 0.001) and in symptomatic individuals, compared with asymptomatic (80.3 ± 92.1 ng/mL vs. 45.4 ± 41.4 ng/mL, p = 0.02). ROC curve analysis identified sST2 cut-off: >98.44 ng/mL as the best predictor for mortality. At the one-year follow-up, the survival rate decreased up to 20% in patients with sST2 higher than the cut-off value. A multivariate regression analysis revealed that only sST2 (HR: 1.012, 95% CI: 1.008–1.016, p < 0.0001) and triglycerides plasma levels (HR: 1.008, 95% CI: 1.002–1.015, p = 0.0135) remained significantly associated with all-cause mortality. ST2L was not associated with all-cause mortality risk. sST2 may act as an independent prognostic determinant of all-cause mortality and symptomatic cerebrovascular diseases in patients with carotid atherosclerotic plaque who underwent CEA.

P387 THE PROGNOSTIC ROLE OF ST2L AND SST2 IN PATIENTS WHO UNDERWENT CAROTID PLAQUE ENDATERECTOMY: A FIVE–YEAR FOLLOW–UP STUDY

Abstract Background Soluble suppressor of tumorigenity (sST)–2 plasma concentrations are related to atherosclerosis. The aim of the study was to assess the prognostic impact of sST2 and its membrane–associated form (ST2L) in patients with carotid atherosclerotic plaque who underwent endarterectomy (CEA). Methods 82 consecutive patients (age range: 48–86 years) who underwent CEA were enrolled. Anthropometric, clinical, instrumental, and laboratory evaluations were gathered. Thirty–seven (45%) patients were symptomatic for cerebrovascular diseases. Patients underwent a five–year follow–up. Phone calls and the analysis of national and regional databases were adopted in order to evaluate the occurrence of the primary outcome (all–cause mortality). The populations was divided according to survival status. Results Statins were administered in 81% and 87.5% of survivors and non–survivors, respectively. sST2 levels were higher in non–survivors as compared to survivors (117.0 ± 103.9 vs 38.0 ± 30.0ng/mL, p &amp;lt; 0.001) and in symptomatic individuals as compared to asymptomatic (80.3 ± 92.1 ng/mL vs 45.4 ± 41.4 ng/mL, p = 0.02). ROC curve analysis identified sST2 cut–off: &amp;gt; 98.44 ng/mL as the best predictor for mortality. At one year follow–up, survival rate decreased up to 20% in patients with sST2 higher than the cut–off value. At multivariate regression analysis sST2 (HR: 1.012, 95% CI: 1.008–1.016, p &amp;lt; 0.0001) and triglycerides plasma levels (HR: 1.008, 95% CI: 1.002–1.015, p = 0.0135) remained significantly associated to all–cause death. Conclusions sST2 may act as independent prognostic determinant of all–cause mortality and symptomatic cerebrovascular diseases in patients with carotid atherosclerotic plaque who underwent CEA.

Timing of Carotid Intervention in Symptomatic Cerebrovascular Disease: Outcomes of a Single-Institution Experience

The optimal timing for carotid endarterectomy in patients with symptomatic cerebrovascular disease has remained unclear. We compared the clinical outcomes of carotid endarterectomy performed before and 2 weeks after symptom onset. A retrospective analysis was performed of patients who had presented to our institution with symptomatic cerebrovascular disease, defined by the presence of transient ischemic attack (TIA) or cardiovascular accident (CVA) symptoms, from January 2012 to February 2020. The data collected included demographics, National Institutes of Health stroke scale (NIHSS) and modified Rankin scale (mRS) scores, and postoperative complications, including recurrent TIA or CVA, myocardial infarction, and death during admission and at discharge. The patients were followed up for 1 year. The primary end points included NIHSS scores, mRS scores, and changes in the scores from baseline to 30 days, with the secondary end points extending to 90 days and 1 year. A total of 169 patients were included, of whom, 58.6% had undergone carotid endarterectomy within 2 weeks of symptom onset. The baseline demographic and clinical characteristics were similar between groups. No differences in the primary or secondary end points were demonstrated at any interval (P = 1.0, P = .77, and P = .4 for the 30-day NIHSS score, mRS score, and 30-day change in the mRS score, respectively; and P = .9, P = .22, and P = .07 for the 90-day NIHSS score, mRS score, and 1-year mRS score, respectively). We found a difference in postoperative complications, including recurrent TIA/CVA, myocardial infarction, and death. A subgroup analysis of interventional neurology involvement was performed; they had evaluated 44.4% of the patients. No further intervention was required for 42.7%, diagnostic cerebral arteriography was performed in 36.0%, and an additional intervention was required for 21.3%. Interventional neurology involvement demonstrated no differences in the primary or secondary end points. Carotid endarterectomy was safe if performed within 2 weeks of symptom onset with equivalent outcomes compared with delayed surgery. Involvement of interventional neurology did not affect the neurologic outcomes for early vs late operative timing.

IDF21-0196 Study of peripheral arterial disease among type 2 diabetes mellitus patients

Background: Diabetes is a complex chronic metabolic disorder, characterized by persistent hyperglycemia because of lack of insulin secretion, insulin resistance, or both. Peripheral arterial disease (PAD) is one of the major recognised diabetic macro vascular complications. It is a marker of generalised systemic atherosclerosis and is closely associated with symptomatic coronary and cerebrovascular disease, hence significant morbidity and mortality. Aim: To study the various risk factors contributing to development of peripheral arterial disease in adult type2 diabetic patients and vasculopathy profile. Method: This was a retrospective analytical descriptive study conducted at internal medicine department on 13 months. Forty-seven type 2 diabetic patients were included. All patients underwent a detailed history which included age, gender, smoking intake, history of diabetes mellitus with duration and treatment. Biochemical characteristics were studied. Diagnosis of PAD was made by using color Doppler ultrasound. The statistical analysis was carried out using Epi-Info7. Results: The study was conducted on 47type2 diabetic patients with a mean age of 66±10 years with male predominance (77%) compared to females (23%). Mean duration of diabetes mellitus was15±9 years. Majority of patients were on insulin (n=22;46.81%). Eleven patients (23.40%) were on combined insulin and OHA. and ten were on oral hypoglycemic agents (OHA) (21.28%). Sixteen (34%) patients were cigarette smokers. Regarding hypertension status, 24 (51.06%) patients were hypertensive. Metabolic syndrome was prevalent in twenty patients, with mean of BMI 25±5 kg/m2. PAD was prevalent in 38(80.85%) patients. Of these, there were 27(57.45%) obliterating arteriopathy of the lower limbs,20(42.55 %) had mediacalcinosis, 10 (21.28 %) had acute arterial occlusion, 8 (17.02%) stenosis, and 2(4.26 %) arterial thrombosis. The prevalence of neuropathy was 46.81% (n=22) and diabetic foot was present in all patients (n=47) of patients. Regarding biochemical parameters: mean of fasting blood glucose was 1.73±0.76g/l, mean of post prandial blood glucose 2.45±0.77g/l, mean of HBA1C 9±3%, mean of HDLc 0.32±0.14 g/l, mean of triglycerides1.56±1.29g/l, mean of creatinine clearance according MDRD equation was 69±41 ml/min/1.73m2, mean of protein C reactive in this population was 88±80mg/l. Discussion: The increasing burden of diabetes is considered as one of the greatest global public health problem of our time. Diabetic patients with PAD are at high risk of increased morbidity and mortality from cardiovascular diseases and a high rate of lower extremity amputation. Various risk factors like age, gender persistant hyperglycemia, increased glycated hemoglobin, smoking and hypertension, and dyslipidaemia are associated with an increased risk of peripheral artery disease. This study documents a high prevalence of PAD among adult type2 diabetic patients. This strongly calls for aggressive screening for PAD be emphasised.

Comparison of Clinical Features between the High and Low Serum KL-6 Patients with Acute Exacerbation of Interstitial Lung Diseases.

Background Serum Krebs von den Lungen-6 (KL-6) measurement is widely used to assess disease activity or prognosis in patients with interstitial lung diseases (ILDs). However, the clinical differences between high and low serum KL-6 levels at the time of acute exacerbation (AE) of ILD are not well known. Methods Clinical parameters including age, sex, Charlson Comorbidity Index score (CCIS), blood biomarkers, high-resolution CT findings, and disease mortality were retrospectively compared between high and low KL-6 (cutoff value: 1000 U/mL) patients at the time of diagnosis of AE of ILDs. Results Thirty-eight high serum KL-6 and 57 low serum KL-6 patients were included. There was no significant difference in 6-month mortality between them (P = 0.685), whereas serum lactate dehydrogenase was a significant predictor of 6-month mortality in the high serum KL-6 patients (odds ratio (OR): 1.006; 95% confidence interval (CI): 1.003–1.009; P < 0.001), and CCIS (OR: 1.502; 95% CI: 1.242–1.838; P < 0.001) and sex (OR: 5.751; 95% CI: 1.121–105.163; P = 0.033) were significant predictors in low serum KL-6 patients. In addition, the incidences of congestive heart failure, symptomatic chronic pulmonary disease, cerebrovascular disease, and second metastatic solid tumours were significantly higher in nonsurvivors with low serum KL-6 than in other groups (P < 0.05). Conclusions The clinical features in patients with AEs of ILDs may differ depending on the serum KL-6 level, and clinicopathological examination according to this subtyping guided by the serum KL-6 level is essential.

Microsurgical training through laboratory experience: A step-by-step practical guideline

BackgroundMicrosurgical laboratory training remains the mainstay to acquire, improve, and perfect surgical abilities. Microvascular anastomotic techniques are of key importance for revascularization procedures, such as in giant cerebral aneurysms, skull base complex tumours, and symptomatic ischemic cerebrovascular diseases. MethodsWe show the techniques, materials, and experience performed in a microsurgical laboratory of a neurosurgical referral center in Mexico City. ResultsWe describe the materials, non-specimen suture practices, specimen manipulation, and finally all the individual procedures we are capable to perform on live specimens. ConclusionsThe microsurgical laboratory is an indispensable tool for the acquisition of the so needed microsurgical skills in neurosurgery, having a very special emphasis in vascular neurosurgery.

Neurovascular Coupling Is Impaired in Hypertensive and Diabetic Subjects Without Symptomatic Cerebrovascular Disease.

The mechanistic link between hypertension, diabetes and cerebral small vessel disease (CSVD) is still poorly understood. We hypothesized that hypertension and diabetes could impair cerebrovascular regulation prior to irreversibly established cerebrovascular disease. In this study, 52 hypertensive patients [54% males; age 64 ± 11 years; 58% with comorbid diabetes mellitus (DM)] without symptomatic cerebrovascular disease underwent transcranial Doppler (TCD) monitoring in the middle (MCA) and posterior (PCA) cerebral arteries, to assess vasoreactivity to carbon dioxide (VRCO2) and neurovascular coupling (NVC). 1.5T magnetic resonance imaging was also performed and white matter hyperintensity volume was automatically segmented from FLAIR sequences. TCD data from 17 healthy controls were obtained for comparison (47% males; age 60 ± 16 years). Hypertensive patients showed significant impairment of NVC in the PCA, with reduced increment in cerebral blood flow velocity during visual stimulation (22.4 ± 9.2 vs. 31.6 ± 5.7, p < 0.001), as well as disturbed NVC time-varying properties, with slower response (lower rate time: 0.00 ± 0.02 vs. 0.03 ± 6.81, p = 0.001), and reduced system oscillation (reduced natural frequency: 0.18 ± 0.08 vs. 0.22 ± 0.06, p < 0.001), when compared to controls. VRCO2 remained relatively preserved in MCA and PCA. These results were worse in hypertensive diabetic patients, with lower natural frequency (p = 0.043) than non-diabetic patients. White matter disease burden did not predict worse NVC. These findings suggest that hypertensive diabetic patients may have a precocious impairment of NVC, already occurring without symptomatic CSVD. Future research is warranted to evaluate whether NVC assessment could be useful as an early, non-invasive, surrogate marker for CSVD.

Systolic Blood Pressure and Outcomes in Stable Outpatients with Recent Symptomatic Artery Disease: A Population-Based Longitudinal Study.

Objectives: The most appropriate targets for systolic blood pressure (SBP) levels to reduce cardiovascular morbidity and mortality in patients with symptomatic artery disease remain controversial. We compared the rate of subsequent ischemic events or death according to mean SBP levels during follow-up. Design: Prospective cohort study. FRENA is an ongoing registry of stable outpatients with symptomatic coronary (CAD), cerebrovascular (CVD) or peripheral artery disease (PAD). Setting: 24 Spanish hospitals. Participants: 4789 stable outpatients with vascular disease. Results: As of June 2017, 4789 patients had been enrolled in different Spanish centres. Of these, 1722 (36%) had CAD, 1383 (29%) CVD and 1684 (35%) PAD. Over a mean follow-up of 18 months, 136 patients suffered subsequent myocardial infarction, 125 had ischemic stroke, 74 underwent limb amputation, and 260 died. On multivariable analysis, CVD patients with mean SBP levels 130–140 mm Hg had a lower risk of mortality than those with levels <130 mm Hg (hazard ratio (HR): 0.39; 95% CI: 0.20–0.77), as did those with levels >140 mm Hg (HR: 0.46; 95% CI: 0.26–0.84). PAD patients with mean SBP levels >140 mm Hg had a lower risk for subsequent ischemic events (HR: 0.57; 95% CI: 0.39–0.83) and those with levels 130–140 mm Hg (HR: 0.47; 95% CI: 0.29–0.78) or >140 mm Hg (HR: 0.32; 95% CI: 0.21–0.50) had a lower risk of mortality. We found no differences in patients with CAD. Conclusions: In this real-world cohort of symptomatic arterial disease patients, most of whom are not eligible for clinical trials, the risk of subsequent events and death varies according to the levels of SBP and the location of previous events. Especially among patients with large artery atherosclerosis, PAD or CVD, SBP <130 mm Hg may result in increased mortality. Due to potential factors in this issue, Prospective, well designed studies are warranted to confirm these observational data.

Association of Ischemic Imaging Phenotype With Progression of Brain Atrophy and Cerebrovascular Lesions on MRI

Background and Objective To investigate the association of silent vascular lesions, imaging negative ischemia, and symptomatic cerebrovascular disease with long-term progression of brain atrophy and cerebrovascular lesions in patients with arterial disease. Methods Within the Second Manifestations of Arterial Disease–Magnetic Resonance (SMART-MR) study, stroke status of participants at baseline was classified as no cerebrovascular disease (reference group, n = 829), symptomatic cerebrovascular disease (n = 206), silent vascular lesion (n = 157), and imaging-negative ischemia (n = 90) according to clinical and MRI findings. With the use of linear mixed models, changes in brain and white matter hyperintensity (WMH) volumes at baseline and during 12 years of follow-up were studied in stroke classifications. Relative risks were estimated for new infarcts during follow-up associated with stroke classifications. Analyses were adjusted for age, sex, cardiovascular risk factors, and medications. Results Symptomatic cerebrovascular disease associated with 0.35 SD (95% confidence interval [CI] 0.24–0.47) smaller brain volume and 0.61 SD (95% CI 0.48–0.74) larger WMH volume at baseline and increased risk for new infarcts during follow-up (risk ratio [RR] 2.89, 95% CI 2.00–4.16). Silent vascular lesions were associated with 0.15 SD (95% CI 0.01–0.88) smaller brain volume, 0.02 SD (95% CI 0.01–0.03) steeper brain atrophy slope, and 0.48 SD (95% CI 0.32–0.64) larger WMH volume at baseline, in addition to increased risk for lacunes (RR 2.08, 95% CI 1.48–2.94). Individuals with imaging-negative ischemia had increased risk for cortical infarcts (RR 2.88, 95% CI 2.17–3.82). Discussion Patients with symptomatic cerebrovascular disease, silent vascular lesions, or imaging-negative ischemia have a different course of brain volume loss and cerebrovascular lesion development. These findings may have implications for future stroke risk and dementia and need further investigation.

Trimethylamine-N-Oxide Levels Are Similar in Asymptomatic vs. Symptomatic Cerebrovascular Atherosclerosis.

Introduction: Trimethylamine-N-oxide (TMAO) is correlated with atherosclerosis and vascular diseases such as coronary heart disease and ischemic stroke. The aim of the study was to investigate whether TMAO levels are different in symptomatic vs. asymptomatic cerebrovascular atherosclerosis.Methods: This was a prospective, case–control study, conducted at a tertiary care university hospital. Patients were included if they had large-artery atherosclerosis (TOAST criteria). Symptomatic patients with ischemic stroke were compared with asymptomatic patients. As primary endpoint, TMAO levels on admission were compared between symptomatic and asymptomatic patients. Univariable analysis was performed using Mann–Whitney U test and multivariable analysis using binary logistic regression. TMAO values were adjusted for glomerular filtration rate (GFR), age, and smoking.Results: Between 2018 and 2020, 82 symptomatic and asymptomatic patients were recruited. Median age was 70 years; 65% were male. Comparing symptomatic (n = 42) and asymptomatic (n = 40) patients, no significant differences were found in univariable analysis in TMAO [3.96 (IQR 2.30–6.73) vs. 5.36 (3.59–8.68) μmol/L; p = 0.055], GFR [87 (72–97) vs. 82 (71–90) ml/min*1.73 m2; p = 0.189] and age [71 (60–79) vs. 69 (67–75) years; p = 0.756]. In multivariable analysis, TMAO was not a predictor of symptomatic cerebrovascular disease after adjusting for age and GFR [OR 1.003 (95% CI: 0.941–1.070); p = 0.920]. In a sensitivity analysis, we only analyzed patients with symptomatic stenosis and excluded patients with occlusion of brain-supplying arteries. Again, TMAO was not a significant predictor of symptomatic stenosis [OR 1.039 (0.965–1.120), p = 0.311].Conclusion: TMAO levels could not be used to differentiate between symptomatic and asymptomatic cerebrovascular disease in our study.

Location of recurrent cardiovascular events and anticardiolipin antibodies.

The relationship between anticardiolipin (aCL) antibodies and cardiovascular events is uncertain and may vary according to arterial location. FRENA is an ongoing registry of stable outpatients with symptomatic coronary artery disease (CAD), cerebrovascular disease (CVD) or peripheral artery disease (PAD). The rate of subsequent ischaemic events was cross-referenced with the presence of aCL antibodies (any isotype, IgG or IgM). As of June 2017, 1387 stable outpatients were recruited. Of these, 120 (8.7%) showed positive levels of aCL antibodies. Over an average follow-up of 18months, 250 patients developed subsequent events: 101 myocardial infarction, 57 ischaemic stroke and 92 critical leg events. Patients with positive aCL antibodies had a higher risk of distal artery events (a composite of ischaemic stroke or critical leg events) than patients with undetectable or low levels (rate ratio: 1.66; 95% CI: 1.07-2.60). However, an association with central coronary events was not found. The multivariate Cox analysis after adjustment for relevant clinical covariates showed that positivity of aCL antibodies is an independent risk factor for distal events (hazard ratio: 1.60; 95% CI: 1.01-2.55; P<.05). Positivity of aCL antibodies is associated with an increased risk of subsequent distal artery ischaemic events (cerebral or leg arteries) but not coronary artery events. Anticardiolipin antibodies appear to have a different relationship on the localisation of ischaemic events in patients with symptomatic artery disease.

Superficial-Temporal-Artery-To-Middle-Cerebral-Artery Bypass in Cerebrovascular Occlusive Disease and Hemodynamic-Related Ischemia: Illustrative Case and Literature Review

AbstractStroke is the third most common cause of death worldwide. About 10% to 15% of strokes related to the territory of the carotid artery are associated with its complete occlusion. There is an important subgroup of patients with cerebrovascular occlusive diseases who might benefit from an external-carotid-to-internal-carotid bypass. In the present study, we report a case of a 53-year-old male patient with stenosis of the M2 branch of the middle cerebral artery (MCA), with a history of ∼ 20 episodes of transient ischemic accidents (TIA)s, in whom an anastomosis of the M4 branch of the superficial temporal artery-MCA was performed. The patient was discharged in three days, and in the two years of follow-up, they were no more TIAs. We also conducted a review of the literature on cerebrovascular occlusive disease and extracranial-intracranial bypass surgery. New methods to evaluate cerebral hemodynamics made it possible to classify a new subgroup of patients with symptomatic cerebrovascular disease and documented cerebrovascular compromise in whom the drug therapy fails, who can benefit from the extracranial-intracranial bypass. Our case report illustrates the advantages of revascularization in these selected patients.