Atherothrombotic Stroke Research Articles

Novel Therapeutic Approaches to Prevent Atherothrombotic Ischemic Stroke in Patients with Carotid Atherosclerosis.

Atherothrombotic stroke represents approximately 20% of all ischemic strokes. It is caused by large-artery atherosclerosis, mostly in the internal carotid artery, and it is associated with a high risk of early recurrence. After an ischemic stroke, tissue plasminogen activator is used in clinical practice, although it is not possible in all patients. In severe clinical situations, such as high carotid stenosis (≥70%), revascularization by carotid endarterectomy or by stent placement is carried out to avoid recurrences. In stroke prevention, the pharmacological recommendations are based on antithrombotic, lipid-lowering, and antihypertensive therapy. Inflammation is a promising target in stroke prevention, particularly in ischemic strokes associated with atherosclerosis. However, the use of anti-inflammatory strategies has been scarcely studied. No clinical trials are clearly successful and most preclinical studies are focused on protection after a stroke. The present review describes novel therapies addressed to counteract inflammation in the prevention of the first-ever or recurrent stroke. The putative clinical use of broad-spectrum and specific anti-inflammatory drugs, such as monoclonal antibodies and microRNAs (miRNAs) as regulators of atherosclerosis, will be outlined. Further studies are necessary to ascertain which patients may benefit from anti-inflammatory agents and how.

THE BENEFITS OF DUPLEX SCANNING OF EXTRACRANIAL CAROTID PATHOLOGIES FOR RISK STRATIFICATION OF ISCHEMIC STROKE

Abstract Introduction: Recent retrospective cohort study demonstrated the benefit of duplex scanning in the examination of the extracranial carotid artery pathologies for preventing cerebrovascular disorders. The aim of this study: was to evaluate the clinical and demographical characteristics and outcome in patients treated at National Scientific Center of Surgery, after detecting extracranial carotid artery stenosis ≥70%. Material and methods: A retrospective cohort study was conducted; 204 patients were included. Results: The most significant risk factors were: ischemic heart diseases – 95.6%, arterial hypertension – 80.1%, chronic heart failure – 83.8%, cholesterol level above the norm of 5.2 mmol/L-39.2%; 30.4% of patients had a history of postinfarction cardiosclerosis. There were a significant statistically difference between the prevalence of extracranial carotid artery stenosis depending on the risk factors (blood cholesterol levels, a clinical history of chronic heart failure, and acute cerebrovascular diseases p=0.048, p=0.003, p=0.048 respectively (p>0.05)). Conclusion: In summary, we conclude that surgery should be considered, and duplex ultrasound plays a crucial role in assessing the severity of carotid stenosis in atherothrombotic stroke patients with severe external carotid stenosis. These data indicate that physicians, should be aware of the usefulness of carotid duplex ultrasound scanning in stratifying the risk of cerebral and cardiovascular diseases based on various aspects.

Особенности анализа ЭЭГ-микросостояний при постинсультной афазии

Knowledge about the specificity of changes in the activity of neural networks associated with realization of thought processes can be used to construct the personalized medical rehabilitation systems. This approach is of particular interest for people with the speech function disturbance due to stroke, since the development of aphasia with the loss of speech leads to severe social maladaptation that worsens the disease outcome. The study was aimed to assess the functional activity of individual neural networks based on the theory of combining the EEG microstate identification technique with the method of determining spatial localization by solving the EEG inverse problem in 27 individuals (15 males and 12 females) with an average age of 52 years, who had speech impairment due to acute atherothrombotic stroke. Mathematical analysis of the scalp bioelectrical activity multichannel recording from the system for EEG microstate model isolation was carried out under changing environmental conditions caused by the auditory-speech load together with the EEG inverse problem solution for each subject. It was found that the speech disorder development depends not only on the fact of damage to brain structures, but also on the deep functional restructuring of both neural streams involved in implementation of brain function and the entire speech connectome. The disease with a predominant motor disorder, that has shown the possibility of transferring functions to the intact hemisphere prefrontal structures, in contrast to sensory disorders representing global changes in the entire speech connectome, can probably be considered the most favorable variant of aphasia.

History of Carotid Artery Reconstruction around the World and in Japan.

Since ancient times, physicians have been aware of correlations between the carotid artery and consciousness; however, carotid stenosis was only recently identified as the cause of atherothrombotic ischemic stroke. In 1658, Wepfer described the first suggestion of a link between symptoms of cerebral arterial insufficiency and carotid pathology. In 1951, Fisher reported details of the symptoms and pathological findings and emphasized that cervical atheromatous lesions induced cerebral infarction with various symptoms. The beginning of carotid artery surgery was ligation of the carotid artery for neck or head injury, but surgeons were aware that this operation induced cerebral symptoms due to lack of blood supply. Carotid endarterectomy (CEA) was first reported by Eastcott et al. in 1954, and in Japan, Kimoto performed a successful CEA in 1962. In 1979, percutaneous transluminal angioplasty (PTA) was performed for patients with fibromuscular dysplasia, and then, carotid artery stenting (CAS) was first performed in 1989 by Mathias. In Japan, Kuwana et al. were the first to perform carotid PTA, in 1981, whereas Yamashita et al. performed the first CAS in 1997. Yoshimura et al. proposed staged carotid stenting to prevent hyperperfusion syndrome. Some issues in carotid reconstruction are still debated today, which include conventional (standard) CEA versus the eversion technique, CEA versus CAS versus medical therapy, and medical economic problems. In the future, we must continue to develop more effective, safer, and less expensive therapeutic methods to prevent carotid stroke, carrying on the efforts of the ancient peoples who pioneered this research.

Prediction of restoration of swallowing function in patients with ischemic stroke and neurogenic dysphagia

Objective: to determine prognostic characteristics of the restoration of swallowing function in patients with ischemic stroke (IS) of various pathogenetic subtypes.Material and methods. The study included 110 patients (64 men and 46 women aged 44–89 years) with dysphagia in the acute period of IS. The SSS-TOAST criteria were used to diagnose the pathogenetic subtype, and the MASA scale was used to determine the presence and severity of dysphagia. To predict the probability of switching to self-feeding depending on the severity of dysphagia, a non-linear regression method was used using the least squares method.Results. Patients with cardioembolic stroke subtype were initially characterized by a greater degree of dysphagia in comparison with patients with atherothrombotic stroke subtype in groups comparable in severity (p<0.05). In the cardioembolic subtype of IS, the probability of switching patients to self-feeding on the 21st day in groups with dysphagia severity from 105 to 135 points on the MASA scale was lower than in the atherothrombotic subtype of IS (p<0.05).Conclusion. Patients with cardioembolic strokes are characterized by more severe initial dysphagia and a worse prognosis for recovery of swallowing function compared to patients with atherothrombotic strokes.

Does Diffusion Restriction Pattern on MRI Predict Stroke Etiology in a Cancer Patient?

Stroke and cancer are two of the most common health problems. Moreover, stroke is more common in patients with cancer than in the normal population, due to coagulation problems. Knowing the etiology of stroke is important for determining treatment options. This study aimed to determine the relationship between ischemic lesion topographies using diffusion-weighted magnetic resonance imaging (MRI) and the etiology of stroke in patients with cancer. All patients with ischemic stroke in the Bezmialem Stroke Registry over a 4- year period were retrospectively analyzed in this study. Patients with acute ischemic stroke and additional diagnoses of solid and active malignancy (excluding hematologic malignancies) were included in the analysis. We investigated whether there was a relationship between the etiology of patients with cancer-related stroke according to the stroke etiologic classification and the diffusion restriction patterns on MRI. In this registry, 32 of 1472 patients were diagnosed as having active cancer. Fourteen patients were evaluated as having definite cardioembolism, eight patients as probable cardioembolism, and four patients had inadequate examinations. Only one patient was classified as having an atherothrombotic stroke. Isolated acute infarction was seen in 15 of 32 patients. In patients with multiple acute infarct areas (n=17), acute lesions characterized by micro embolisms in a single vessel area were detected in four patients, and acute lesions characterized by bilateral (anterior and/or posterior system) micro embolisms in more than one vessel area in 13 patients. The most common etiology of stroke in patients with cancer was found to be embolic/ cardioembolic. This is important for the treatment plans for ischemic stroke in patients with cancer.

Endothelial CCRL2 induced by disturbed flow promotes atherosclerosis via chemerin-dependent β2 integrin activation in monocytes.

Chemoattractants and their cognate receptors are essential for leucocyte recruitment during atherogenesis, and atherosclerotic plaques preferentially occur at predilection sites of the arterial wall with disturbed flow (d-flow). In profiling the endothelial expression of atypical chemoattractant receptors (ACKRs), we found that Ackr5 (CCRL2) was up-regulated in an endothelial subpopulation by atherosclerotic stimulation. We therefore investigated the role of CCRL2 and its ligand chemerin in atherosclerosis and the underlying mechanism. By analysing scRNA-seq data of the left carotid artery under d-flow and scRNA-seq datasets GSE131776 of ApoE-/- mice from the Gene Expression Omnibus database, we found that CCRL2 was up-regulated in one subpopulation of endothelial cells in response to d-flow stimulation and atherosclerosis. Using CCRL2-/-ApoE-/- mice, we showed that CCRL2 deficiency protected against plaque formation primarily in the d-flow areas of the aortic arch in ApoE-/- mice fed high-fat diet. Disturbed flow induced the expression of vascular endothelial CCRL2, recruiting chemerin, which caused leucocyte adhesion to the endothelium. Surprisingly, instead of binding to monocytic CMKLR1, chemerin was found to activate β2 integrin, enhancing ERK1/2 phosphorylation and monocyte adhesion. Moreover, chemerin was found to have protein disulfide isomerase-like enzymatic activity, which was responsible for the interaction of chemerin with β2 integrin, as identified by a Di-E-GSSG assay and a proximity ligation assay. For clinical relevance, relatively high serum levels of chemerin were found in patients with acute atherothrombotic stroke compared to healthy individuals. Our findings indicate that d-flow-induced CCRL2 promotes atherosclerotic plaque formation via a novel CCRL2-chemerin-β2 integrin axis, providing potential targets for the prevention or therapeutic intervention of atherosclerosis.

Identification of the relationship between biomarkers of autophagy, apoptosis and inflammation in the acute period of atherothrombotic ischemic stroke

The postischemic inflammatory response plays a significant role in the pathogenesis of acute ischemic stroke (IS). It has been established that acute IS is accompanied by aseptic inflammation, which induces the activation of costimulatory molecules in the process of innate immunity response to brain tissue damage. The constantly progressive destruction of neuronal antigens contributes to an increase in the volume of the ischemic lesion. Evidence continues to accumulate indicating an important role of NLRP3-mediated inflammation in the pathogenesis of IS. It has been shown that autophagy is involved in the inflammatory cascade in acute IS. Many of the anti-inflammatory mechanisms mediated by autophagy in acute IS involve the key autophagic proteins Beclin-1, LC3, and p62. Experimental studies have shown that autophagy suppresses the activation of NLRP3 inflammation. Data on cross interactions between apoptosis and autophagy in the pathogenesis of IS are still controversial. The aim of the study was to evaluate the relationship between biomarkers of autophagy, inflammation, and apoptosis in the dynamics of the acute period of atherothrombotic IS. The article presents the results of a dynamic study of the serum concentration of the key autophagy biomarkers Beclin-1, LC3 and p62, apoptosis indicators Bcl-2 and p53, pro-inflammatory cytokines IL-1β, TNFα, IL-8, IL-18 which are involved in postischemic neuroinflammation. A statistically significant increase in the studied parameters was established in comparison with the control group. The maximum increase in the studied biomarkers is noted on the 1st day after the development of ischemia in patients with a severe course of the disease. The relationship between autophagy activity, apoptosis biomarkers, and some indicators of the systemic inflammatory response in patients with moderate and severe atherothrombotic stroke was revealed. The results obtained confirm the literature data on the involvement of autophagy in the regulation of the postischemic inflammatory response.

CYP metabolic pathway related gene polymorphism increases the risk of embolic and atherothrombotic stroke and vulnerable carotid plaque in southeast China

ObjectiveTo investigate the association of CYP metabolic pathway-related genetic polymorphisms with the susceptibility to ischemic stroke and stability of carotid plaque in southeast China. MethodsWe consecutively enrolled 294 acute ischemic stroke patients with carotid plaque and 282 controls from Wenling First People's Hospital. The patients were divided into the carotid vulnerable plaque group and stable plaque group according to the results of carotid B-mode ultrasonography. Polymorphisms of CYP3A5 (G6986A, rs776746), CYP2C9*2 (C430T, rs1799853), CYP2C9*3 (A1075C, rs1057910), and EPHX2 (G860A, rs751141) were determined using polymerase chain reaction and mass spectrometry analysis. ResultsEPHX2 GG may reduce the susceptibility to ischemic stroke (OR = 0.520, 95% CI: 0.288 ∼ 0.940, P = 0.030) and AA+AG may increase the risk for ischemic stroke (OR = 1.748, 95% CI: 1.001 ∼ 3.052, P = 0.050). The distribution of CYP3A5 genotypes showed significant differences between the vulnerable plaque and stable plaque groups (P = 0.026). Multivariate logistic regression analysis found that CYP3A5 GG could reduce the risk of vulnerable plaques (OR = 0.405, 95% CI: 0.178 ∼ 0.920, P = 0.031). ConclusionEPHX2 G860A polymorphism may reduce the stroke susceptibility, while other SNPs of CYP genes are not associated with ischemic stroke in southeast China. Furthermore CYP3A5 polymorphism was related with carotid plaque instability.

Therapeutic Strategies for Ischemic Stroke

Ischemic stroke therapy consists of acute phase and preventive treatment strategies. Acute-phase ischemic stroke treatment includes systemic thrombolysis (rt-PA) and mechanical thrombectomy (endovascular therapy). Rt-PA is a very potent thrombolytic agent but its effectiveness is time-dependent. For the prevention of stroke recurrence (secondary stroke prevention) according to the TOAST classification, antiplatelet therapy (aspirin, clopidogrel, and cilostazol) is used for atherothrombotic and lacuna strokes, while anti-coagulant therapy (warfarin and direct oral anticoagulants [DOACs]) are used for cardiogenic cerebral embolism. Additionally, neuroprotective therapy using edaravone, a free radical scavenger, has recently been introduced to minimize brain tissue damage. Recently, neuronal regenerative therapies using stem cells have also been developed.

Potential circulating biomarkers of atherosclerotic plaque vulnerability in patients in the early recovery period of atherothrombotic stroke

Despite the informative value of ultrasound examination of atherosclerotic vascular lesions, predicting­ the plaque vulnerabili­ty remains difficult. Circulating blood biomarkers could provide additional criteria that would allow better determination of the risk of recurrent stroke. The aim of our study was to estimate the level of C-reactive protein (CRP), low-density lipoproteins (LDL) and lipoprotein-associated phospholipase A2 (Lp-PLA2) in the blood of patients in the early recovery period of atherothrombotic stroke depending on the density of atherosclerotic plaque according to duplex scanning of cerebral vessels. Clinical and laboratory analysis of 69 men and 61 women aged (60.42 ± 7.40) years in the early recovery period of atherothrombotic stroke was conducted. Depending on the structure of the atherosclerotic plaque the examinees were divided into two groups with stable (n = 80) and unstable (n = 50) atherosclerotic layers. The blood lipid spectrum was examined on a biochemical analyzer Screen master, the level of CRP was determined with a diagnostic kit and that of Lp-PLA2 by ELISA. Significantly higher levels of LDL, CRP and Lp-PLA2 were observed in patients with unstable atherosclerotic plaque compared to patients with stable atherosclerotic plaque in the early recovery period of atherothrombotic stroke. The increased level of LDL, CRP, and Lp-PLA2 in patients with cerebral atherosclerosis can be considered as an indicator of the vulnerability of atherosclerotic plaques, prone to rupture, and as a prognostic marker of repeated acute ischemic events. Keywords: atherosclerotic plaque, C-reactive protein, lipoprotein-associated phospholipase A2, low density lipoproteins, recovery period of ischemic stroke

The thrombus proteome in stroke reveals a key role of the innate immune system and new insights associated with its etiology, severity, and prognosis

BackgroundNowadays little is known about the molecular profile of the occluding thrombus of patients with ischemic stroke. ObjectivesTo analyze the proteomic profile of thrombi in patients who experienced an ischemic stroke in order to gain insights into disease pathogenesis. MethodsThrombi from an exploratory cohort of patients who experienced a stroke were obtained by thrombectomy and analyzed by sequential window acquisition of all theoretical spectra-mass spectrometry. Unsupervised k-means clustering analysis was performed to stratify patients who experienced a stroke. The proteomic profile was associated with both the neurological function (National Institute of Health Stroke Scale [NIHSS]) and the cerebral involvement (Alberta Stroke Program Early CT Score [ASPECTS]) prior to thrombectomy and the clinical status of patients at 3 months using the modified Rankin Scale. In an independent cohort of 210 patients who experienced a stroke, the potential role of neutrophils in stroke severity was interrogated. ResultsProteomic analysis identified 580 proteins in thrombi, which were stratified into 4 groups: hemostasis, proteasome and neurological diseases, structural proteins, and innate immune system and neutrophils. The thrombus proteome identified 3 clusters of patients with distinctive severity, prognosis, and etiology of the stroke. A protein signature clearly distinguished atherothrombotic and cardioembolic strokes. Several proteins were significantly correlated with the severity of the stroke (NIHSS and ASPECTS). Functional proteomic analysis highlighted the prominent role of neutrophils in stroke severity. This was in line with the association of neutrophil activation markers and count with NIHSS, ASPECTS, and the modified Rankin Scale score 90 days after the event. ConclusionThe use of sequential window acquisition of all theoretical spectra-mass spectrometry in thrombi from patients who experienced an ischemic stroke has provided new insights into pathways and players involved in its etiology, severity, and prognosis. The prominent role of the innate immune system identified might pave the way for the development of new biomarkers and therapeutic approaches in this disease.

Role of osteoprotegerin rs3102735 gene polymorphism in acute ischemic stroke patients

BackgroundIschemic stroke ranks third among leading causes of death and disability. Both endothelial and vascular smooth muscle cells generate osteoprotegerin (OPG). Ischemic stroke and its severity may be enhanced by the OPG rs3102735 gene polymorphism. Our research aims to investigate OPG rs3102735 gene polymorphism role in ischemic stroke risk and to assess its association with stroke severity at presentation and degree of vascular stenosis and evaluate its potential as a predictor of stroke severity. Fifty people with acute ischemic stroke as well as fifty controls were studied. The NIHSS and ASPECTS were utilized to evaluate stroke severity and the infarction size, respectively. All subjects underwent extracranial carotid duplex study and molecular assessment for genotyping of OPG rs3102735) gene polymorphism.ResultsStroke patients had markedly higher concentrations of OPG in the plasma than controls (311.60 ± 109.48 versus 240.20 ± 75.96 mmol/ml, p = 0.001). The optimal plasma OPG cutoff value for the predicting the occurrence of stroke was determined to be > 250 mmol/ml, the 95% confidence interval (CI) was (0.625–0.843), sensitivity was 68% and specificity was 72%. Ischemic stroke had a significantly different genotype distribution for the OPG rs3102735 gene polymorphism than did controls (36 CC, 13 CT, and 1 TT) versus (28 CC, 15 CT, and 7 TT) respectively. Stroke patients had a significantly greater CC + CT genotype than controls did (P = 0.041), also they had a higher propensity for carrying the C allele than the T allele (P = 0.017). Carotid intima medium thickness and the NIHSS both had positive correlations with OPG serum level (r = 0.39, p = 0.02 and r = 0.4, p = 0.02, respectively), whereas ASPECTS had an inversed correlation (r = − 0.65, p = 0.001).ConclusionsThe current study shows that as an independent risk factor, increased plasma OPG level, may participate in the atherothrombotic ischemic stroke pathophysiology, in addition, genetic variants in the OPG gene (rs3102735) are a separate risk factor for large artery atherosclerosis and plasma OPG level can serve as a biomarker to determine the severity of a stroke.

Diffusion-weighted Imaging and Arterial Spin Labeling for Prediction of Cerebral Infarct Volume in Acute Atherothrombotic Stroke.

This study aims to investigate the usefulness of diffusion-weighted imaging (DWI) and arterial spin labeling (ASL) for predicting final infarct volume in patients with acute atherothrombotic subtype cerebral infarction (AT-type stroke). The data of 77 patients with AT-type stroke were retrospectively analyzed. ASL and DWI values of minimum apparent diffusion coefficient (min ADC), mean ADC (mean ADC), minimum cerebral blood flow (min CBF), and mean CBF (mean CBF) of the infarction lesions were measured. Changes in cerebral infarction volume (ΔVolume) were determined by DWI reexamination on the 7th day after onset. Correlations of ADC and CBF with Δ Volume were analyzed. Receiver operating characteristic (ROC) curve analysis was used to determine the usefulness of ADC and CBF values for predicting final infarct volume. There was a significant difference in the distribution of the ΔVolume in AT-type stroke (P<0.0001). The ADC and min CBF values were negatively correlated with the infarct ΔVolume (P<0.05); mean CBF and ΔCBF were not correlated with ΔVolume. When min ADC was ≤0.303 × 10-3 mm2/s, min CBF 1.5 ≤2.415 mL/100 g/min, or min CBF2.5 ≤4.25 mL/100 g/min, ΔVolume was likely to be large. The ROC curve showed the highest predictive value for min ADC and min CBF. Distinctive patterns of quantitative ADC and CBF can be used as a simple and rapid method for predicting change in infarction volume in AT-type stroke.

Effect of plasma thrombin-antithrombin complex on ischemic stroke: a systematic review and meta-analysis

Background and objectiveThrombin-antithrombin complex (TAT) is a prethrombotic marker, and its application in ischemic stroke is still uncertain. The purpose of this systematic review and meta-analysis is to evaluate the relationship between plasma TAT and ischemic stroke base on the current evidence.MethodsA systematic literature search was conducted for searching the relative studies that investigated the association of TAT and ischemic stroke in PubMed, EMBASE, and Cochrane library databases. Mean difference and 95% confidence interval as the effect sizes were synthesized by random effects model in Review Manager (RevMan) Version 5.4. The heterogeneity was investigated using the chi-square test and the possible sources of heterogeneity were explored by sensitivity analysis and meta-regression. The publication bias was estimated by Egger’s tests.ResultsA total of 12 eligible studies were included involving 1431 stroke cases and 532 healthy controls, of which six studies were eventually included in the meta-analysis. Plasma TAT in patients with ischemic stroke was significantly higher than that in healthy controls (MD 5.31, 95% CI = 4.12–6.51, P < 0.0001, I2 = 97.8%). There is a difference of TAT level in the same period among cardioembolic, lacunar, and atherothrombotic stroke (all P < 0.0001), in which the cardioembolic stroke with the highest level. Meanwhile, it is significant of TAT levels among various phases of cardioembolic stroke and the acute phase are markedly elevated (MD 7.75, 95CI%, 6.07–9.43, P < 0.001). However, no difference was found in the atherothrombotic (P = 0.13) and lacunar stroke (P = 0.34). Besides, the higher TAT level is closely related to the poor prognosis of patients with ischemic stroke, including higher recurrence, mortality, unfavorable recovery (modified Rankin scale > 2), and poor revascularization.ConclusionsThis study suggested that plasma TAT levels are different in ischemic stroke subtypes, which are closely associated with the progression and might have an effect on the prognosis.Systematic review registrationPROSPERO CRD: 42021248787

Electronegative LDL Is Associated with Plaque Vulnerability in Patients with Ischemic Stroke and Carotid Atherosclerosis

Owing to the high risk of recurrence, identifying indicators of carotid plaque vulnerability in atherothrombotic ischemic stroke is essential. In this study, we aimed to identify modified LDLs and antioxidant enzymes associated with plaque vulnerability in plasma from patients with a recent ischemic stroke and carotid atherosclerosis. Patients underwent an ultrasound, a CT-angiography, and an 18F-FDG PET. A blood sample was obtained from patients (n = 64, 57.8% with stenosis ≥50%) and healthy controls (n = 24). Compared to the controls, patients showed lower levels of total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein B (apoB), apoA-I, apoA-II, and apoE, and higher levels of apoJ. Patients showed lower platelet-activating factor acetylhydrolase (PAF-AH) and paraoxonase-1 (PON-1) enzymatic activities in HDL, and higher plasma levels of oxidized LDL (oxLDL) and electronegative LDL (LDL(-)). The only difference between patients with stenosis ≥50% and <50% was the proportion of LDL(-). In a multivariable logistic regression analysis, the levels of LDL(-), but not of oxLDL, were independently associated with the degree of carotid stenosis (OR: 5.40, CI: 1.15-25.44, p < 0.033), the presence of hypoechoic plaque (OR: 7.52, CI: 1.26-44.83, p < 0.027), and of diffuse neovessels (OR: 10.77, CI: 1.21-95.93, p < 0.033), indicating that an increased proportion of LDL(-) is associated with vulnerable atherosclerotic plaque.

Unexplored Roles of Erythrocytes in Atherothrombotic Stroke.

Stroke constitutes the second highest cause of morbidity and mortality worldwide while also impacting the world economy, triggering substantial financial burden in national health systems. High levels of blood glucose, homocysteine, and cholesterol are causative factors for atherothrombosis. These molecules induce erythrocyte dysfunction, which can culminate in atherosclerosis, thrombosis, thrombus stabilization, and post-stroke hypoxia. Glucose, toxic lipids, and homocysteine result in erythrocyte oxidative stress. This leads to phosphatidylserine exposure, promoting phagocytosis. Phagocytosis by endothelial cells, intraplaque macrophages, and vascular smooth muscle cells contribute to the expansion of the atherosclerotic plaque. In addition, oxidative stress-induced erythrocytes and endothelial cell arginase upregulation limit the pool for nitric oxide synthesis, leading to endothelial activation. Increased arginase activity may also lead to the formation of polyamines, which limit the deformability of red blood cells, hence facilitating erythrophagocytosis. Erythrocytes can also participate in the activation of platelets through the release of ADP and ATP and the activation of death receptors and pro-thrombin. Damaged erythrocytes can also associate with neutrophil extracellular traps and subsequently activate T lymphocytes. In addition, reduced levels of CD47 protein in the surface of red blood cells can also lead to erythrophagocytosis and a reduced association with fibrinogen. In the ischemic tissue, impaired erythrocyte 2,3 biphosphoglycerate, because of obesity or aging, can also favor hypoxic brain inflammation, while the release of damage molecules can lead to further erythrocyte dysfunction and death.

Ictus isquémico. Infarto cerebral y ataque isquémico transitorio

Ischemic stroke is defined as dysfunction in a region of the central nervous system as a consequence of a stoppage in focal perfusion. It can be subdivided into cerebral infarction or transitory ischemic attack (TIA) depending on whether the ischemia lasts long enough to cause tissue necrosis. According to the etiological classification of the Spanish Society of Neurology's Cerebrovascular Disease Study Group, ischemic stroke is subdivided into atherothrombotic stroke, cardioembolic stroke, lacunar stroke, stroke of unusual cause, or stroke of undetermined cause. The secondary prevention strategy is different for each type. Arriving at a correct diagnosis of cerebral infarction is fundamental to being able to provide appropriate treatment in the acute phase and thus revert the symptoms and improve patients’ functional prognosis. In addition, the study of the stroke's cause will lead to an improvement in secondary prevention and must be as comprehensive as possible.

Ictus isquémico de causa inhabitual y criptogénico. Trombosis venosa cerebral

Ischemic stroke of unusual cause is that in which the cause is something other than atherothrombotic stroke, cardioembolic stroke, or small vessel disease. Of note among the causes are non-arteriosclerotic arterial diseases (non-inflammatory, infectious, and non-infectious inflammatory diseases), hematological abnormalities, and stroke associated with cancer. Cryptogenic stroke is that in which, after a full study, the cause of the stroke is not able to be identified. According to case series and depending on the etiological classification used, cryptogenic stroke can represent 30% to 40% of stroke cases. Cerebral venous sinus thrombosis (CVST) is an uncommon disease that represents 1% of all strokes; it is more common in young patients. The factors that predispose an individual to developing CVST are varied (genetic or acquired prothrombotic state, local infections, inflammatory diseases, or mechanical factors after neurosurgical interventions or trauma, among others). Its clinical manifestations depend on the thrombosed cerebral venous sinus, though headache, focal symptoms, and seizures are the most characteristic. In this update, the main causes of stroke of unusual origin, the diagnostic strategy in cryptogenic stroke, and the diagnostic and treatment approach to CVST are reviewed.

Monitoring the Antiplatelet Therapy Efficacy in Patients with Acute Ischemic Stroke.

Stroke is one of the leading causes of morbidity and mortality in populations of developed countries. Ischemic strokes account for 85 - 90% of all strokes, with the majority of strokes of non-cardioembolic pathogenesis. Platelet aggregation plays a key role in arterial thrombus formation. Therefore, effective antiplatelet therapy plays a key role in secondary prevention. Acetylsalicylic acid (ASA) is the main drug of choice, and clopidogrel therapy is another recommended treatment option. Monitoring of the efficacy of antiplatelet therapy has been intensively studied in patients with coronary artery disease in the context of coronary stent implantation. It is not yet part of the routine procedure in patients with stroke [1-3]. This study investigated the efficacy of antiplatelet therapy with ASA and clopidogrel using optical and impedance aggregometry in 42 consecutive patients with acute ischemic stroke. Patients were treated with throm-bolysis at baseline and platelet function was examined 24 hours after administration, focusing on the occurrence of platelet hyperaggregability and assessing the efficacy of any chronically administered antiplatelet therapy. Subsequently, patients were administered a loading dose of ASA or clopidogrel followed by a check of its efficacy 24 hours after administration. In the following days, the maintenance dose of the drug was continued and regular laboratory monitoring of treatment efficacy was performed every 24 hours. In patients with atherothrombotic stroke indicated for antiplatelet therapy, monitoring of residual platelet activity allowed for detection of potentially atrisk patients. These were 35% (9% borderline ineffective) of patients taking ASA and 55% (18% borderline ineffective) of patients treated with clopidogrel. The dose was adjusted, increased the administered treatment and no recurrence of stroke was observed in this study group at 1-year follow-up. Personalized antiplatelet therapy based on platelet function tests appears to be a useful method to reduce the risk of recurrent vascular events.