Search Results (14)

Silent Brain Infarction (SBI) is increasingly recognized in patients with cardiac conditions, particularly Atrial Fibrillation (AF) in elderly patients and those undergoing Transcatheter Aortic Valve Implantation (TAVI). While these infarcts often go unnoticed due to a lack of acute symptoms, they are associated with a threefold increase in stroke risk and are considered a precursor to ischemic stroke. Moreover, accumulating evidence suggests that SBI may contribute to the development of dementia, depression, and cognitive decline, particularly in the elderly population. The burden of SBI is substantial, with studies showing that up to 11 million Americans may experience a silent stroke annually. In AF patients, silent brain infarcts are common and can lead to progressive brain damage, even in those receiving anticoagulation therapy. The use of cerebral embolic protection devices (CEPDs) during TAVI has been explored to mitigate the risk of stroke; however, their efficacy remains under debate. Despite advancements in TAVI technology, cerebrovascular events, including silent brain lesions, continue to pose significant challenges, underscoring the need for improved preventive strategies and therapeutic approaches. We propose a device consisting of a strut structure placed at the base of the treated artery to model the potential risk of cerebral embolisms caused by atrial fibrillation, thromboembolism, or dislodged debris of varying potential TAVI patients. The study has been carried out in two stages. Both are based on computational fluid dynamics (CFD) coupled with the Lagrangian particle tracking method. The first stage of the work evaluates a variety of strut thicknesses and inter-strut spacings, contrasting with the device-free baseline geometry. The analysis is carried out by imposing flow rate waveforms characteristic of healthy and AF patients. Boundary conditions are calibrated to reproduce physiological flow rates and pressures in a patient’s aortic arch. In the second stage, the optimal geometric design from the first stage was employed, with the addition of lateral struts to prevent the filtration of particles and electronegatively charged strut surfaces, studying the effect of electrical forces on the clots if they are considered charged. Flowrate boundary conditions were used to emulate both healthy and AF conditions. Results from numerical simulations coming from the first stage indicate that the device blocks particles of sizes larger than the inter-strut spacing. It was found that lateral strut space had the highest impact on efficacy. Based on the results of the second stage, deploying the electronegatively charged device in all three aortic arch arteries, the number of particles entering these arteries was reduced on average by $62.6$% and $51.2$%, for the healthy and diseased models respectively, matching or surpassing current oral anticoagulant efficacy. In conclusion, the device demonstrated a two-fold mechanism for filtering emboli: (1) while the smallest particles are deflected by electrostatic repulsion, avoiding micro embolisms, which could lead to cognitive impairment, the largest ones are mechanically filtered since they cannot fit in between the struts, effectively blocking the full range of particle sizes analyzed in this study. The device presented in this manuscript offers an anticoagulant-free method to prevent stroke and SBIs, imperative given the growing population of AF and elderly patients. Full article

Sickle cell disease (SCD) is a hereditary blood disorder characterized by abnormal hemoglobin, leading to the sickle shape of red blood cells. It has several vascular complications and the cerebrovascular ones are among the most frequent and severe both in children and in adults. This review summarizes the main neurovascular manifestations of SCD, including acute stroke, silent cerebral infarction, large-vessel diseases (moyamoya arteriopathy and aneurysms), and brain bleeding. Both epidemiology, pathophysiology, and treatment issues are addressed and prevention of cerebrovascular events, including silent cerebral infarctions, is particularly relevant in SCD patients, being associated to poor functional outcome and cognitive complaints. Transfusions and hydroxyurea are the main available therapy at the moment, but contraindications, availability, and complications might prevent their long term use, particularly in low-income countries. The role of transcranial Doppler in monitoring the patients (mainly children) is analyzed and a practical approach has been selected in order to give the main messages from the current literature for a better management of SCD patients. Full article

Patients with chronic kidney disease (CKD) have a higher risk ofboth ischemic and hemorrhagic stroke. This association appears to be partly independent from the higher prevalence of established risk factors for stroke in patients with CKD, including hypertension and atrial fibrillation. In the present review we aim to discuss the impact of CKD on the risk of stroke and stroke-related consequences, and explore the pathophysiology underpinning the increased risk of stroke in patients with CKD. We cover the clinical association between renal dysfunction and cerebrovascular disease including stroke, silent brain infarct, cerebral small vessel disease, microbleeds, and white matter hyperintensity, and discuss the underlying mechanisms. Full article

Background: There is an urgent need to better understand the mechanisms underlying acute and long-term neurological symptoms after COVID-19. Neuropathological studies can contribute to a better understanding of some of these mechanisms. Methods: We conducted a detailed postmortem neuropathological analysis of 32 patients who died due to COVID-19 during 2020 and 2021 in Austria. Results: All cases showed diffuse white matter damage with a diffuse microglial activation of a variable severity, including one case of hemorrhagic leukoencephalopathy. Some cases revealed mild inflammatory changes, including olfactory neuritis (25%), nodular brainstem encephalitis (31%), and cranial nerve neuritis (6%), which were similar to those observed in non-COVID-19 severely ill patients. One previously immunosuppressed patient developed acute herpes simplex encephalitis. Acute vascular pathologies (acute infarcts 22%, vascular thrombosis 12%, diffuse hypoxic–ischemic brain damage 40%) and pre-existing small vessel diseases (34%) were frequent findings. Moreover, silent neurodegenerative pathologies in elderly persons were common (AD neuropathologic changes 32%, age-related neuronal and glial tau pathologies 22%, Lewy bodies 9%, argyrophilic grain disease 12.5%, TDP43 pathology 6%). Conclusions: Our results support some previous neuropathological findings of apparently multifactorial and most likely indirect brain damage in the context of SARS-CoV-2 infection rather than virus-specific damage, and they are in line with the recent experimental data on SARS-CoV-2-related diffuse white matter damage, microglial activation, and cytokine release. Full article

Sickle cell disease (SCD) is the most common inherited single-gene disease. Complications include chronic anaemia, reduced oxygen-carrying capability, and cerebral vasculopathy, resulting in silent cerebral infarction, stroke, and cognitive dysfunction with impairments in measures of executive function, attention, reasoning, language, memory, and IQ. This systematic review aims to investigate the association between neuroimaging findings and cognition in children with SCD. Searches of PubMed and Embase were conducted in March 2022. Studies were included if participants were <18 years, if original data were published in English between 1960 and 2022, if any genotype of SCD was included, and if the relationship between cognition and neuroimaging was examined. Exclusion criteria included case studies, editorials, and reviews. Quality was assessed using the Critical Appraisal Skills Programme Case Control Checklist. A total of 303 articles were retrieved; 33 met the eligibility criteria. The presence of overt or silent strokes, elevated blood flow velocities, abnormal functional connectivity, and decreased fMRI activation were associated with neuropsychological deficits in children with SCD when compared to controls. There is a critical need to address the disease manifestations of SCD early, as damage appears to begin at a young age. Most studies were cross-sectional, restricting the interpretation of the directionality of relationships. Future research employing longitudinal neuroimaging and neuropsychological assessments could improve our understanding of the cumulative consequences of SCD on the developing brain. Full article

(1) Objective: to investigate the association between the total burden of cerebral small vessel disease (CSVD) and cognitive function in Parkinson’s disease (PD). (2) Methods: this retrospective study compared clinical and neuroimaging characteristics of 122 PD patients to determine the association between cognitive decline and total burden of CSVD in PD. All patients underwent brain MRI examinations, and their total CSVD burden scores were evaluated by silent lacunar infarction (SLI), cerebral microbleeds (CMB), white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS). The cognitive function was assessed by administering Mini-Mental State Examination (MMSE). Receiver-operating characteristic (ROC) curve and the area under the ROC curve (AUC) were performed to quantify the accuracy of the total burden of CSVD and PVH in discriminating PD patients with or without cognitive impairment. (3) Results: the PD patients with cognitive impairment had a significantly higher SLI, CMB, periventricular hyperintensities (PVH), deep white matter hyperintensities (DWMH), enlarged perivascular spaces of basal ganglia (BG-EPVS), and the total CSVD score compared with no cognitive impairment. Total CSVD score and MMSE had a significant negative correlation (r = −0. 483). Furthermore, total burden of CSVD and PVH were the independent risk factors of cognitive impairment in PD, and their good accuracy in discriminating PD patients with cognitive impairment from those with no cognitive impairment was confirmed by the results of ROC curves. (4) Conclusions: total burden of CSVD tightly linked to cognitive impairment in PD patients. The total burden of CSVD or PVH may predict the cognitive impairment in PD. Full article

This review outlines the current clinical research investigating how the haptoglobin (Hp) genetic polymorphism and stroke occurrence are implicated in sickle cell disease (SCD) pathophysiology. Hp is a blood serum glycoprotein responsible for binding and removing toxic free hemoglobin from the vasculature. The role of Hp in patients with SCD is critical in combating blood toxicity, inflammation, oxidative stress, and even stroke. Ischemic stroke occurs when a blocked vessel decreases oxygen delivery in the blood to cerebral tissue and is commonly associated with SCD. Due to the malformed red blood cells of sickle hemoglobin S, blockage of blood flow is much more prevalent in patients with SCD. This review is the first to evaluate the role of the Hp polymorphism in the incidence of stroke in patients with SCD. Overall, the data compiled in this review suggest that further studies should be conducted to reveal and evaluate potential clinical advancements for gene therapy and Hp infusions. Full article

Objective: The aims of this study are to analyze the role of artery-vein ratio AVR assessment using VesselMap 2 software (Imedos Systems) and cardiovascular risk evaluation by means of REGICOR in the prediction of silent brain infarction (SBI) in middle-age hypertensive patients from the ISSYS study. Material and Methods: A cross-sectional study with 695 patients with hypertension aged 50 to 70 years who participated in the project Investigating Silent Strokes in HYpertensives: a Magnetic Resonance Imaging Study (ISSYS), was conducted in two Primary Care Centres of Barcelona. Participants agreed to a retinography and an MRI to detect silent brain infarction (SBI). The IMEDOS software was used for the semiautomatic caliber measurement of retinal arteries and veins, and the AVR was considered abnormal when <0.66. The REGICOR score was calculated for all patients. Results: Multivariate logistic regression analysis was used to evaluate the impact of AVR and REGICOR scores on SBI. The OR (odds ratio) for a high REGICOR score and an abnormal AVR were 3.16 and 4.45, respectively. When analysing the interaction of both factors, the OR of an abnormal AVR and moderate REGICOR score was 3.27, whereas with a high REGICOR score it reached 13.07. Conclusions: The measurement of AVR in patients with hypertension and with a high REGICOR score can contribute to the detection of silent brain infarction. Full article

Thymidylate synthase (TS) is a key gene involved in the repair of DNA damage and DNA synthesis that plays an important role in vascular development and recovery. In particular, TS gene polymorphisms play a major role in the progression of vascular disease and cancer metastasis. Therefore, the aim of this study was to investigate the association of three TS polymorphisms (1100T>C [rs699517], 1170A>G [rs2790], and 1494ins/del [rs151264360]) with ischemic stroke and silent brain infarction (SBI) in Koreans. A total of 1299 participants (507 stroke patients, 383 SBI patients, and 409 controls) were enrolled in the study. Genotyping of the three TS polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. To examine the association between TS gene polymorphisms and the diseases, we performed statistical analyses, including multivariable logistic regression and Fisher’s exact tests. We found that TS 1100T>C and 1170A>G genotypes were strongly associated with ischemic stroke and SBI susceptibility. More specifically, the TS 1100T>C polymorphism was associated with the likelihood of ischemic stroke (TT vs. CC: AOR = 2.151, 95% CI = 1.275–3.628, P = 0.004) and SBI (TT vs. TC+CC: AOR = 1.443, 95 % CI = 1.009–2.063, P = 0.045). In contrast, the TS 1170A > G polymorphism exhibited lower correlation with the risk of stroke (AA vs. GG: AOR = 0.284, 95% CI = 0.151–0.537, P < 0.0001) and SBI (AA vs. GG: AOR = 0.070, 95% CI = 0.016–0.298, P = 0.0002). Furthermore, we confirmed that the TS 1100T>C polymorphism was synergistic with low folic acid levels (AOR = 6.749, P < 0.0001). Altogether, these results suggest that TS 1100T>C and 1170A > G polymorphisms are associated with the risk of ischemic stroke and SBI, and our study provides the first evidence that 3′-UTR variants in TS are potential biomarkers in ischemic stroke and SBI. Full article

Obesity is known to increase the risk of stroke. It is unclear whether high absolute fat mass (FM) increases the risk of stroke independently. We studied the correlation between FM and silent brain infarction/white matter change (SI/WMC) using brain computed tomography. We selected subjects from the local government health promotion project. We randomly selected a target population that had never been diagnosed with stroke or dementia. FM was measured by bioelectrical impedance analysis (BIA). We divided the subjects into three groups according to the FM (gender-specific tertiles [GTx]). Seven hundred and twenty-two subjects (321 men) between 50 and 75 years of age were recruited. The overall odds ratio (OR) of SI/WMC was 2.23 (95% confidence interval (CI), 1.34–3.71; p = 0.002) times higher in the 37th to 100th percentiles (GT₃) than in the first to 32nd percentiles (GT₁). When men and women were separated, the OR of GT₃ was 1.35 (CI, 0.62–2.94; p = 0.45) in men and 3.2 (CI, 1.60–6.40; p = 0.001) in women. The findings were not found to be statistically significant after adjusting for the well-known stroke risk factors. When the subjects were divided into a high FM (HFMG, GT₃) and low FM group (LFMG, GT₁ + GT₂), the HFMG showed an increased OR of SI/WMC in women. Similar results were seen after adjusted (overall: OR, 1.38; CI, 0.85–2.25, p = 0.198; men: OR, 0.93; CI, 0.422–2.051; p = 0.86; women: OR, 2.02; CI, 1.06–3.86; p = 0.03). The findings suggest that high FM may be an independent risk factor for ischemic stroke among adults free from stroke and dementia, especially in women. Full article

The aim of this paper is to correlate the extent of silent cerebral infarcts (SCIs) on magnetic resonance imaging (MRI) with the clinical severity of sickle cell disease (SCD) in adult patients. Twenty-four consecutive adult asymptomatic SCD patients (11 male and 13 female) with a mean age of 38.4 years (range 20–59) were submitted to brain MRI on a 1 Tesla Gyroscan Intera, Philips MR scanner with a dedicated head coil. The protocol consisted of TSE T2-weighted and FLAIR images on the axial and coronal planes. MRI readings were undertaken by two radiologists and consensus readings. Patients were compound heterozygotes (HbS/β-thal). The extent of SCIs was classified from 0–2 with 0 designating no lesions. Clinical severity was graded as 0–2 by the hematologist, according to the frequency and severity of vaso-occlusive crises. There was no statistically significant correlation between the severity of clinical disease and the extent of SCIs on MR imaging. The extent of SCI lesions did not differ statistically between younger and older patients. Patients receiving hydroxyurea had no statistically significant difference in the extent of SCI lesions. The extent of SCIs in heterozygous (HbS/β-thal) SCD patients is not age related and may be quite severe even in younger (<38.4 years) patients. However the extent of SCIs is not correlated with the severity of clinical disease. Full article

Sickle Cell Disease(SCD) is one of the most common hemoglobinopathies in the world which causes stroke. The management of stroke depends on the manifestations and the age of the patient. Especially in childhood, anatomic and physiological abnormalities of CNS may be a predisposing factors. Stroke mostly affects the distal segments of the Internal Carotid Artery, but also middle and anterior segments of the cerebral arteries are involved. The most important predisposing factors are the arterial malformations, stenosis and obstructions in cranial arteries, generally involving Internal Carotid Artery, frequently Proximal Middle Cerebral or Anterior Cerebral Arteries. After infarcts at brain vessels, most frequent clinical findings are hemiparesis or hemiplegia, impaired speech, focal seizures, gait disturbances. Risk factors for predisposing stroke are prior transient ischemia, baseline Hb decrease, acute chest sydrome within previous two weeks, systolic blood pressure rises, leucocyte increases. The patient with silent stroke or transient ischemic attacks may be asymptomatic or without neurological symptoms. Neuroimaging abnormalities may be seen without significant clinical findings in children with SCD. We talk about silent stroke if there are neuroradiological abnormalities without clinical findings. Children with silent strokes are more prone to new strokes. If there is a significant stroke a ischemic stroke often present with focal neurological signs and symptoms. If patient is asymptomatic or have suspected stroke, first step may be performance of Transcranial Doppler Ultrasonography (TCD). Children with time-averaged mean velocity (TAMV), measured in Middle Carotid Artery or in distal internal carotid Artery abnormally elevated, defined as TAMV ≥ 200 cm/sec, have sixfold increase for stroke than those with normal TAMV ≤ 170 cm/sec. For these patients under the risk of stroke, chronic blood transfusion is recommended for prevention of primary stroke events. Because of high oxygene demand in children, the child with SCD who also has anemia is at particular risk. The management of acute stroke includes to rule out hemorrhage, stabilize vital signs, careful use of hydration and RBCs transfusion. Exchange blood with normal RBCs is mandatory; it will improve tissue perfusion and oxygenation. Long-term management of stroke is directed to prevent recurrences with fluids supplementation, a chronic transfusion programme at least for 6 months with exchange transfusion or erythrocytapheresis for reducing the HbS under 30%. After 3 years of HbS levels to be maintained <30%, the HbS leveles can be raised safely to less than 50% if the patient has remained neurologically stable. Indefinite chronic transfusion programme was advised for the patients with abnormal TCD values. Hydroxyurea (HU) is an alternative therapy in reducing TCD values and to try to increase HbF improving the clinical outcome. Periodical cranial Doppler ultrasound examination and selective red blood cell transfusions ‘d be useful for stroke prevention.
镰状细胞病(SCD)是世上最常见的血红蛋白病，可致中风 中风防治受症状表现和病人的年龄所左右。 尤其对于患儿，中枢神经系统的组织异常和生理异常可能是诱病因素。 中风通常影响颈内动脉的末端，但也会牵连到脑动脉的中段和前段。 中风最重要的诱病因素有动脉畸形、器官狭窄和大脑动脉阻塞，一般和到颈内动脉有关，但牵连到大脑中动脉或大脑前动脉更为常见。 脑血管梗塞后，通常临床发现轻偏瘫或偏瘫、语言障碍、病灶性颠痫和步态障碍等。 诱病性中风具有的风险包括：前两周内引起短暂性局部缺血、血红蛋白含量减少和急性胸痛综合症，然后导致收缩压升高和白血球增加。 轻度中风或短暂性脑缺血发作的患者可能无症候或无神經症狀。 在没重大临床发现的情况下，镰状细胞病患儿可做脑神经成像检查，异常亦会发现。 下边我们将讨论无临床表现情况下神经放射性异常。 轻度中风的患儿再次中风的可能性很大。 如果中风严重，脑缺血的出现经常伴随着局部性神經系統症候和症状 如果患者无症候或疑似中风，首先应进行经颅多普勒超声（TCD）检查。 在异常抬升的中动脉或内动脉末端测量时间平均血流速度(TAMV)，结果为TAMV ≥ 200 cm/sec，该患者中风的可能性是正常情况（TAMV ≤ 170 cm/sec）的六倍。建议对有中风危险的患者采取慢速输血的方法，以防止主要中风事件。 由于儿童对氧的需求量高，患镰状细胞病同时伴有贫血的儿童危险系数尤其高。 急性中风防治的措施包括：排除溢血的可能性、稳定生命体征、谨慎利用水和作用和（血红细胞）RBCs输血 必须使用正常的RBCs交换血液；提高组织灌注和氧化作用。 中风的长期防治旨在阻止再次补充液体，用交换输血或红细胞除去法慢速输血至少6个月，以便把血红蛋白含量减少到30%以下。 血红蛋白含量 < 30% 保持3年后，如果患者神经稳定，可将其升高到50%以下。 TCD值不正常的患者，建议采取不定期慢速输血程序。 作为降低TCU值的备用疗法，羟基脲（HU）尝试提高HbF的含量，达到改善临床结果的目的。 防止中风有效的措施包括定期对大脑进行多普勒超声检查和有选择性的进行血红细胞输血。 Full article

Recent evidence has indicated that active and passive cigarette smoking are associated, in a dose-dependent manner, with dysfunction of normal endothelial physiology. Tobacco smoke (TS) may predispose individuals to atherogenic and thrombotic problems, significantly increasing the risk for ischemic manifestations such as acute coronary syndrome and stroke. Despite the strong evidence for an association between smoking and vascular impairment, the impact of TS exposure on the blood-brain barrier (BBB) has only been marginally addressed. This is a major problem given that the BBB is crucial in the maintenance of brain homeostasis. Recent data have also shown that chronic smokers have a higher incidence of small vessel ischemic disease (SVID), a pathological condition characterized by leaky brain microvessels and loss of BBB integrity. In the brain TS increases the risk of silent cerebral infarction (SCI) and stroke owing to the pro-coagulant and atherogenic effects of smoking. In this article we provide a detailed review and analysis of current knowledge of the pathophysiology of tobacco smoke toxicity at the cerebrovascular levels. We also discuss the potential toxicity of recently marketed “potential-reduced exposure products”. Full article

Lysophosphatidic acid (LPA), which is proposed to play an important role in normal physiological situations such as wound healing, vascular tone, vascular integrity and reproduction, may be involved in the etiology of some diseases such as atherosclerosis, cancer, obesity or myocardial infarction. Abnormal findings, including silent brain infarction (SBI), are frequently observed by magnetic resonance imaging (MRI) in patients with nonvalvular atrial fibrillation (NVAF). However, whether there is a relationship between LPA level and the prevalence of SBI has not been extensively studied. In the present study, the association between them was investigated. 235 patients with NVAF, 116 cases of SBI without NVAF and 120 cases of healthy volunteers (control group), who did not receive any antithrombotic therapy, were enrolled in this study. Plasma LPA levels in the NVAF with SBI group were significantly higher than that in the control group (p < 0.01), NVAF without SBI group (p < 0.01) and SBI without NVAF group (p < 0.01). The LPA levels are lower in the control group than in the NVAF without SBI and SBI without NVAF groups (p < 0.01), however, the latter two groups did not significantly differ from each other for LPA levels (p > 0.05) There were significant differences in the positive rate of platelet activation between each of the groups (p < 0.01). The positive rate of platelet activation was significantly higher in the NVAF with SBI group. We suggest that LPA might be a novel marker for estimation of the status of platelet activation and the risk factor for SBI onset in NVAF patients. We expected that plasma LPA levels could predict the occurrence of SBI in NVAF patients. Full article