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Background: Existing studies have already shown a connection between nitrogen dioxide (NO2) exposure and cerebrovascular mortality. However, the differential effects of NO2 on cerebrovascular disease and its subtypes remain unclear and require further exploration. Methods: Daily stroke mortality data between 2013 and 2021 in Shanghai, China were collected. Residential daily air pollution data for each decedent were predicted from a satellite model. An individual-level, time-stratified, case-crossover design was applied to examine the relationship between NO2 exposure and cerebrovascular mortality. A combination of conditional logistic regression and distributed lag models with a maximum lag of 7 days was used for data analysis. Results: A total of 219,147 cases of cerebrovascular mortality were recorded. Among them, the proportion of sequelae of cerebrovascular disease, hemorrhagic stroke and ischemic stroke was 50.7%, 17.1% and 27.5%, respectively. The monotonic increases in mortality risks of cerebrovascular diseases, sequelae of cerebrovascular disease and ischemic stroke were observed, without any discernible thresholds. Each 10 μg/m3 increase in NO2 concentration was associated with increments of 3.62% [95% confidence interval (CI): 2.56%, 4.69%] for total cerebrovascular mortality, 4.29% (95% CI: 2.81%, 5.80%) for sequelae of cerebrovascular disease mortality and 4.30% (95% CI: 2.30%, 6.33%) for ischemic stroke mortality. No positive associations between NO2 exposure and hemorrhagic stroke mortality were observed. A greater risk of NO2 was observed in the warm season, in patients with less than 9 years of education and in those with single marital status. The effects of NO2 were robust to mutual adjustment of co-pollutants. Conclusions: Short-term exposures to NO2 may increase the risk of cerebrovascular mortality, specifically for ischemic stroke and sequelae of cerebrovascular disease.

Nurses play an important role in healthcare, and the Nursing Outcomes Classification is a key tool for the standardization of care. This study aims to validate the nursing outcome “Neurological Status” for patients with cerebrovascular diseases. A methodological study was performed in four phases. In Phase 1, the relevance of the indicators was evaluated by seven specialists and the modified kappa coefficient and content validity index were calculated. In Phase 2, conceptual and operational definitions were formulated. In addition, their content was validated with a focus group in Phase 3. In Phase 4, the results were applied in clinical practice and convergence with the National Institute of Health Stroke Scale was verified. The reliability was measured by Cronbach’s alpha. Of the 22 initial indicators, 6 were excluded. The focus group suggested changes in the definitions and the exclusion of two indicators. In Phase 4, only 13 indicators were validated due to the impossibility of measuring intracranial pressure. A strong correlation between the two scales and agreement among all the indicators were observed. Following the specialists’ review, the nursing outcome was reliable and clinically validated with 13 indicators: consciousness, orientation, language, central motor control, cranial sensory and motor function, spinal sensory and motor function, body temperature, blood pressure, heart rate, eye movement pattern, pupil size, pupil reactivity, and breathing pattern.

Stroke remains a major cause of death and disability worldwide. Identifying new circulating biomarkers able to distinguish and monitor common and rare cerebrovascular diseases that lead to stroke is of great importance. Biomarkers provide complementary information that may improve diagnosis, prognosis and prediction of progression as well. Furthermore, biomarkers can contribute to filling the gap in knowledge concerning the underlying disease mechanisms by pointing out novel potential therapeutic targets for personalized medicine. If many “conventional” lipid biomarkers are already known to exert a relevant role in cerebrovascular diseases, the aim of our study is to review novel “unconventional” lipid biomarkers that have been recently identified in common and rare cerebrovascular disorders using novel, cutting-edge lipidomic approaches.

The determinants of blood pressure variability (BPV) are complex. We aimed to evaluate whether circulating high-sensitivity C-reactive protein (hsCRP) is associated with short-term BPV during the subacute stage of ischemic stroke. In this observational study, a consecutive series of acute ischemic stroke patients who underwent 24 h ambulator blood pressure monitoring (ABPM) during day 4 to 10 after onset were enrolled. Multivariable linear regression models were constructed to assess relationships between hsCRP and BPV. Among a total of 325 patients analyzed, the mean age was 60 years old and 72% were male. The SD, CV, ARV of 24 h SBP and DBP were more likely to be higher in patients with hsCRP ≥ 2 mg/L, and these predispositions remained unchanged in linear regression analyses after adjusting for possible confounding factors, with a dose-response relationship when patients were additionally categorized into quartiles according to hsCRP levels using the lowest quartile as a reference category. In contrast, similar results were observed for the mean of SBP but not the mean of DBP. These results indicate that hsCRP is dose-dependently associated with short-term BPV during the subacute stage of ischemic stroke. These findings suggested that patients with a higher level of hsCRP tended to have larger blood pressure fluctuations.

Cerebral cavernous malformation (CCM) or cavernoma is a major vascular disease of genetic origin, whose main phenotypes occur in the central nervous system, and is currently devoid of pharmacological therapeutic strategies. Cavernomas can remain asymptomatic during a lifetime or manifest with a wide range of symptoms, including recurrent headaches, seizures, strokes, and intracerebral hemorrhages. Loss-of-function mutations in KRIT1/CCM1 are responsible for more than 50% of all familial cases, and have been clearly shown to affect cellular junctions, redox homeostasis, inflammatory responses, and angiogenesis. In this study, we investigated the therapeutic effects of multidrug-loaded lipid nanoemulsions in rescuing the pathological phenotype of CCM disease. The pro-autophagic rapamycin, antioxidant avenanthramide, and antiangiogenic bevacizumab were loaded into nanoemulsions, with the aim of reducing the major molecular dysfunctions associated with cavernomas. Through Western blot analysis of biomarkers in an in vitro CCM model, we demonstrated that drug-loaded lipid nanoemulsions rescue antioxidant responses, reactivate autophagy, and reduce the effect of pro-angiogenic factors better than the free drugs. Our results show the importance of developing a combinatorial preventive and therapeutic approach to reduce the risk of lesion formation and inhibit or completely revert the multiple hallmarks that characterize the pathogenesis and progression of cavernomas.

Acute spontaneous intracerebral hemorrhage (ICH) is the most severe stroke subtype, with a high risk of death, dependence, and dementia. Knowledge about the clinical profile and early outcomes of ICH patients with lobar versus deep subcortical brain topography remains limited. In this study, we investigated the effects of ICH topography on demographics, cerebrovascular risk factors, clinical characteristics, and early outcomes in a sample of 298 consecutive acute ICH patients (165 with lobar and 133 with subcortical hemorrhagic stroke) available in a single-center-based stroke registry over 24 years. The multiple logistic regression analysis shows that variables independently associated with lobar ICH were early seizures (OR 6.81, CI 95% 1.27–5.15), chronic liver disease (OR 4.55, 95% CI 1.03–20.15), hemianopia (OR 2.55, 95% CI 1.26–5.15), headaches (OR 1.90, 95% CI 1.90, 95% IC 1.06–3.41), alcohol abuse (>80 gr/day) (OR 0–10, 95% CI 0.02–0,53), hypertension (OR 0,41, 95% CI 0.23–0–70), sensory deficit (OR 0.43, 95% CI 0.25–0.75), and limb weakness (OR: 0.47, 95% CI 0.24–0.93). The in-hospital mortality was 26.7% for lobar and 16.5% for subcortical ICH. The study confirmed that the clinical spectrum, prognosis, and early mortality of patients with ICH depend on the site of bleeding, with a more severe early prognosis in lobar intracerebral hemorrhage.

Cardiovascular diseases (CVDs) are the leading cause of death and illness in Europe and worldwide, responsible for a staggering 47% of deaths in Europe. Over the past few years, there has been increasing evidence pointing to bioactive sphingolipids as drivers of CVDs. Among them, most studies place emphasis on the cardiovascular effect of ceramides and sphingosine-1-phosphate (S1P), reporting correlation between their aberrant expression and CVD risk factors. In experimental in vivo models, pharmacological inhibition of de novo ceramide synthesis averts the development of diabetes, atherosclerosis, hypertension and heart failure. In humans, levels of circulating sphingolipids have been suggested as prognostic indicators for a broad spectrum of diseases. This article provides a comprehensive review of sphingolipids’ contribution to cardiovascular, cerebrovascular and metabolic diseases, focusing on the latest experimental and clinical findings. Cumulatively, these studies indicate that monitoring sphingolipid level alterations could allow for better assessment of cardiovascular disease progression and/or severity, and also suggest them as a potential target for future therapeutic intervention. Some approaches may include the down-regulation of specific sphingolipid species levels in the circulation, by inhibiting critical enzymes that catalyze ceramide metabolism, such as ceramidases, sphingomyelinases and sphingosine kinases. Therefore, manipulation of the sphingolipid pathway may be a promising strategy for the treatment of cardio- and cerebrovascular diseases.

Neurons are the basic building blocks of the human body’s neurological system. Atrophy is defined by the disintegration of the connections between cells that enable them to communicate. Peripheral neuropathy and demyelinating disorders, as well as cerebrovascular illnesses and central nervous system (CNS) inflammatory diseases, have all been linked to brain damage, including Parkinson’s disease (PD). It turns out that these diseases have a direct impact on brain atrophy. However, it may take some time after the onset of one of these diseases for this atrophy to be clearly diagnosed. With the emergence of the Coronavirus disease 2019 (COVID-19) pandemic, there were several clinical observations of COVID-19 patients. Among those observations is that the virus can cause any of the diseases that can lead to brain atrophy. Here we shed light on the research that tracked the relationship of these diseases to the COVID-19 virus. The importance of this review is that it is the first to link the relationship between the Coronavirus and diseases that cause brain atrophy. It also indicates the indirect role of the virus in dystrophy.

Background: Cerebral cavernous malformations (CCMs) are a major type of cerebrovascular lesions of proven genetic origin that occur in either sporadic (sCCM) or familial (fCCM) forms, the latter being inherited as an autosomal dominant condition linked to loss-of-function mutations in three known CCM genes. In contrast to fCCMs, sCCMs are rarely linked to mutations in CCM genes and are instead commonly and peculiarly associated with developmental venous anomalies (DVAs), suggesting distinct origins and common pathogenic mechanisms. Case report: A hemorrhagic sCCM in the right frontal lobe of the brain was surgically excised from a symptomatic 3 year old patient, preserving intact and pervious the associated DVA. MRI follow-up examination performed periodically up to 15 years after neurosurgery intervention demonstrated complete removal of the CCM lesion and no residual or relapse signs. However, 18 years after surgery, the patient experienced acute episodes of paresthesia due to a distant recurrence of a new hemorrhagic CCM lesion located within the same area as the previous one. A new surgical intervention was, therefore, necessary, which was again limited to the CCM without affecting the pre-existing DVA. Subsequent follow-up examination by contrast-enhanced MRI evidenced a persistent pattern of signal-intensity abnormalities in the bed of the DVA, including hyperintense gliotic areas, suggesting chronic inflammatory conditions. Conclusions: This case report highlights the possibility of long-term distant recurrence of hemorrhagic sCCMs associated with a DVA, suggesting that such recurrence is secondary to focal sterile inflammatory conditions generated by the DVA.

Background: Vertigo is an uncommon symptom among acute stroke victims. Knowledge about the clinical profile, the brain location, and the early outcome in stroke patients with cerebrovascular diseases and vertigo remains limited. Objectives: In this study, the effects of vertigo on cerebral topography and early prognosis in cerebrovascular diseases were investigated. Methods: A comparative analysis in terms of demographics, risk factors, clinical characteristics, stroke subtypes, cerebral and vascular topography, and early outcome was performed between patients with presence or absence of vertigo on a sample of 3743 consecutive acute stroke patients available from a 24-year ongoing single-center hospital-based stroke registry. Results: Vertigo was present in 147 patients (3.9%). Multiple logistic regression analysis showed that variables independently associated with vertigo were: location in the cerebellum (OR 5.59, CI 95% 3.24–9.64), nausea or vomiting (OR 4.48, CI 95% 2.95–6.82), medulla (OR 2.87, CI 95% 1.31–6.30), pons (OR 2.39, CI 95% 1.26–4.51), basilar artery (OR 2.36, CI 95% 1.33–4.17), ataxia (OR 2.33, CI 95% 1.41–3.85), and headache (OR 2.31, CI 95% 1.53–3.49). Conclusion: The study confirmed that the presence of vertigo was not related with increased in-hospital mortality or poor prognosis at hospital discharge. Vertigo is mainly related to non-lacunar vertebrobasilar stroke with topographic localization in the cerebellum and/or brainstem.

Cerebrovascular disease is one of the leading causes of disability and death worldwide, and seeking a potential treatment is essential. Trilinolein (TriL) is a natural triacylglycerol presented in several plants. The effects of TriL on cerebrovascular diseases such as cerebral ischemia and carotid stenosis have never been studied. Accordingly, we investigated the protection of TriL on cerebral ischemia/reperfusion (I/R) and vascular smooth muscle cell (VSMC) migration in vivo and in vitro. The cerebral infarction area, the intima to media area (I/M ratio), and proliferating cell nuclear antigen (PCNA)-staining of the carotid artery were measured. Platelet-derived growth factor (PDGF)-BB-stimulated A7r5 cell migration and potential mechanisms of TriL were investigated by wound healing, transwell, and Western blotting. TriL (50, 100, and 200 mg/kg, p.o.) reduced: the cerebral infarction area; neurological deficit; TUNEL-positive apoptosis; intimal hyperplasia; and PCNA-positive cells in rodents. TriL (5, 10, and 20 µM) significantly inhibited PDGF-BB-stimulated A7r5 cell migration and reduced matrix metalloproteinase-2 (MMP-2), Ras, MEK, and p-ERK protein levels in PDGF-BB-stimulated A7r5 cells. TriL is protective in models of I/R-induced brain injury, carotid artery ligation-induced intimal hyperplasia, and VSMC migration both in vivo and in vitro. TriL could be potentially efficacious in preventing cerebral ischemia and cerebrovascular diseases.

Neurological diseases such as stroke and multiple sclerosis are associated with high morbidity and mortality, long-term disability, and social and economic burden. Therefore, they represent a major challenge for medical treatment. Numerous evidences support the beneficial effects of polyphenols from olive trees, which can alleviate or even prevent demyelination, neurodegeneration, cerebrovascular diseases, and stroke. Polyphenols from olive oils, especially extra virgin olive oil, olive leaves, olive leaf extract, and from other olive tree derivatives, alleviate inflammation and oxidative stress, two major factors in demyelination. In addition, they reduce the risk of stroke due to their multiple anti-stroke effects, such as anti-atherosclerotic, antihypertensive, antioxidant, anti-inflammatory, hypocholesterolemic, hypoglycemic, and anti-thrombotic effects. In addition, olive polyphenols have beneficial effects on the plasma lipid profiles and insulin sensitivity in obese individuals. This review provides an updated version of the beneficial properties and mechanisms of action of olive polyphenols against demyelination in the prevention/mitigation of multiple sclerosis, the most common non-traumatic neurological cause of impairment in younger adults, and against cerebral insult with increasing incidence, that has already reached epidemic proportions.

Background: Enteral nutrition is often prescribed in acute stroke to meet energy and fluid needs in patients with dysphagia. Tubes clogging represent a common complication of enteral formula delivery, requiring substitution and influencing nutrition administration. Frequent water flushes are recommended as one of the most effective procedures to prevent tube occlusion, but it might be time demanding and not consistently performed by the healthcare staff. This study aimed to assess the efficacy of an automatic flush pump, compared to a manual flush system, to prevent tubes’ occlusions in acute-stroke patients, as this might affect nutrition and hydration. Methods: Gastrointestinal symptoms, nutrition and hydration biomarkers were also monitored to determine the different devices’ safety. Sixty-two patients were included in the study and allocated to the “manual” or “automatic” flushes device. Results: The mean duration of data collection was 7 ± 2 days. Tube occlusions occurred in 22.6% of the patients in the “manual” group, whereas only one tube clogging was reported in the “automatic” group (p = 0.023). No significant differences between groups were reported for constipation and diarrhea frequency nor nutrition and hydration status. When the nurses were asked to simulate manual flush administration at the same frequency of the automatic device, they were able to meet the recommendations only 10% of the time. Conclusion: This preliminary study suggests the efficacy of automatic flush systems to prevent enteral tube clogging, without affecting health status compared to standard manual flush systems.

Patients with intracranial artery stenosis show high incidence of stroke. Angiography reports contain rich but underutilized information that can enable the detection of cerebrovascular diseases. This study evaluated various natural language processing (NLP) techniques to accurately identify eleven intracranial artery stenosis from angiography reports. Three NLP models, including a rule-based model, a recurrent neural network (RNN), and a contextualized language model, XLNet, were developed and evaluated by internal–external cross-validation. In this study, angiography reports from two independent medical centers (9614 for training and internal validation testing and 315 as external validation) were assessed. The internal testing results showed that XLNet had the best performance, with a receiver operating characteristic curve (AUROC) ranging from 0.97 to 0.99 using eleven targeted arteries. The rule-based model attained an AUROC from 0.92 to 0.96, and the RNN long short-term memory model attained an AUROC from 0.95 to 0.97. The study showed the potential application of NLP techniques such as the XLNet model for the routine and automatic screening of patients with high risk of intracranial artery stenosis using angiography reports. However, the NLP models were investigated based on relatively small sample sizes with very different report writing styles and a prevalence of stenosis case distributions, revealing challenges for model generalization.

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are administered as first-line therapy for hypercholesterolemia, both as primary and secondary prevention. Besides the lipid-lowering effect, statins have been suggested to inhibit the development of cardiovascular disease through anti-inflammatory, antioxidant, vascular endothelial function-improving, plaque-stabilizing, and platelet aggregation-inhibiting effects. The preventive effect of statins on atherothrombotic stroke has been well established, but statins can influence other cerebrovascular diseases. This suggests that statins have many neuroprotective effects in addition to lowering cholesterol. Furthermore, research suggests that statins cause pro-apoptotic, growth-inhibitory, and pro-differentiation effects in various malignancies. Preclinical and clinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. The pleiotropic effects of statins on cardiovascular and cerebrovascular diseases have been well established; however, the effects of statins on cancer patients have not been fully elucidated and are still controversial. This review discusses the recent evidence on the effects of statins on cardiovascular and cerebrovascular diseases and cancer. Additionally, this study describes the pharmacological action of statins, focusing on the aspect of ‘beyond lipid-lowering’.

A high percentage of patients with COVID-19 (coronavirus disease 2019) have previous cardiovascular disease (CVD). The findings presented here came from an epidemiological population-based registry study (real-world data) that enrolled all in-hospital COVID-19 patients with previous CVD from 1 March to 31 May 2020. Death, other comorbidities, hospital stay variables, ventilation type, and main clinical outcomes were evaluated. In Castile and Leon, 35.83% of the 7307 in-hospital COVID-19 patients who participated in this study had previous CVD, particularly arrhythmias (48.97%), cerebrovascular disease (25.02%), ischemic heart disease (22.8%), and chronic heart failure (20.82%). Of the patients, 21.36% were men and more than 90% were over 65 years of age, and the mortality rate achieved 32.93%. The most used medicines were antibiotics (91.41%), antimalarials (73.3%), steroids (46.64%), and antivirals (43.16%). The main predictors of death were age over 65 years (OR: 5), ventilation needs (OR: 2.81), treatment with anti-SIRS (systemic inflammatory response syndrome) medicines (OR: 1.97), antivirals (OR: 1.74) or steroids (OR: 1.68), SIRS (OR: 5.75), SARS (severe acute respiratory syndrome) (OR: 2.44), or AKI (acute kidney injury) (OR: 1.63) occurrence. Chronic heart failure and cerebrovascular disease were associated with a worse clinical course of COVID-19, especially in men older than 65 years with diabetes who developed SIRS, SARS, or AKI.

New predictors of ischemic incidents are constantly sought since they raise the awareness of patients and their doctors of stroke occurrence. The goal was to verify whether Advanced Glycation End Products (AGEs), in particular AGE10, could be one of them. The AGE10 measurement was conducted using a non-commercial ELISA assay in the blood serum of neurological patients without cerebrovascular event (n = 24), those with transient brain attack (TIA) (n = 17), and severe ischemic stroke (n = 35). Twice as many of the people with TIA or severe stroke presented high AGE10 serum concentrations compared to the patients with other neurological conditions (χ 2 = 8.2, p = 0.004; χ 2 = 8.0, p = 0.005, respectively). The risk of ischemic incident was significantly risen in people with higher levels of AGE10 (OR = 6.5, CI95%: 1.7-24.8; OR = 4.7, CI95%: 1.5-14.5 for TIA and stroke subjects, respectively). We observed a positive correlation (r = 0.40) between high AGE10 levels and diabetes. Moreover, all the diabetic patients that had a high AGE10 content experienced either a severe ischemic stroke or TIA. The patients with high levels of AGE10 exhibited higher grades of disability assessed by the NIHSS scale (r = 0.35). AGE10 can be considered a new biomarker of ischemic stroke risk. Patients with diabetes presenting high AGE10 levels are particularly prone to the occurrence of cerebrovascular incidents.

Background: Existing studies have already shown a connection between nitrogen dioxide (NO 2 ) exposure and cerebrovascular mortality. However, the differential effects of NO 2 on cerebrovascular disease and its subtypes remain unclear and require further exploration., Methods: Daily stroke mortality data between 2013 and 2021 in Shanghai, China were collected. Residential daily air pollution data for each decedent were predicted from a satellite model. An individual-level, time-stratified, case-crossover design was applied to examine the relationship between NO 2 exposure and cerebrovascular mortality. A combination of conditional logistic regression and distributed lag models with a maximum lag of 7 days was used for data analysis., Results: A total of 219,147 cases of cerebrovascular mortality were recorded. Among them, the proportion of sequelae of cerebrovascular disease, hemorrhagic stroke and ischemic stroke was 50.7%, 17.1% and 27.5%, respectively. The monotonic increases in mortality risks of cerebrovascular diseases, sequelae of cerebrovascular disease and ischemic stroke were observed, without any discernible thresholds. Each 10 μg/m 3 increase in NO 2 concentration was associated with increments of 3.62% [95% confidence interval (CI): 2.56%, 4.69%] for total cerebrovascular mortality, 4.29% (95% CI: 2.81%, 5.80%) for sequelae of cerebrovascular disease mortality and 4.30% (95% CI: 2.30%, 6.33%) for ischemic stroke mortality. No positive associations between NO 2 exposure and hemorrhagic stroke mortality were observed. A greater risk of NO 2 was observed in the warm season, in patients with less than 9 years of education and in those with single marital status. The effects of NO 2 were robust to mutual adjustment of co-pollutants., Conclusions: Short-term exposures to NO 2 may increase the risk of cerebrovascular mortality, specifically for ischemic stroke and sequelae of cerebrovascular disease.

Background: The combined use of clopidogrel and aspirin is recommended for the short-term (21 days) therapy of minor stroke or transient ischemic attack. Previous studies have demonstrated its efficacy and superiority over treatment with a single antiplatelet agent. However, there is insufficient support for the advantages of such therapy based on platelet function testing. We aimed to compare the effect of the concomitant use of clopidogrel and aspirin versus clopidogrel alone on the dynamics of platelet reactivity over time to determine the appropriate antiplatelet treatment strategy for minor strokes. Methods: We enrolled 74 ischemic stroke subjects, including 38 minor strokes. Platelet reactivity was assessed by impedance aggregometry (Multiplate Analyzer) 48 and 96 h after a first 75 mg dose of clopidogrel, using the acetylsalicylic acid platelet inhibition (ASPI) test and the adenosine diphosphate (ADP) test. Dual antiplatelet therapy was strictly reserved only to minor strokes, as the other strokes received clopidogrel alone in the secondary prevention. The dynamics of platelet reactivity refer to the difference between two assessments, and a decrease in values over time was considered favorable. Results: The incidence of clopidogrel non-responsiveness was 64.8%, and this was similar in the group of minor strokes and the group of more disabling strokes. We indicated diabetes mellitus as an independent predictor of high on-clopidogrel platelet reactivity (Odds ratio OR 5.69 95% Confidence Interval CI 1.13–41.26, p = 0.0386). Among minor strokes treated with dual antiplatelet therapy, in relation to clopidogrel, we reported a trend toward more favorable dynamics of platelet reactivity over time compared to the group using clopidogrel alone (p = 0.0652 vs. p = 0.3384, respectively). We identified five predictors (sex, female; small-vessel disease; no diabetes; no hyperlipidemia; and no alcohol abuse) related to a significant decrease in platelet reactivity over time with respect to clopidogrel. No significant dynamics of platelet reactivity when using aspirin were found. Conclusions: Our findings, based on the favorable dynamics of platelet reactivity over time in relation to clopidogrel, confirm the usefulness of dual antiplatelet therapy in minor strokes and support the continuation of the secondary prevention with clopidogrel alone rather than aspirin, particularly among identified beneficiaries of such a strategy.

Background: It is often challenging to formulate a reliable prognosis for patients with acute ischemic stroke. The most accepted prognostic factors may not be sufficient to predict the recovery process. In this view, describing the evolution of motor deficits over time via sensors might be useful for strengthening the prognostic model. Our aim was to assess whether an actigraphic-based parameter (Asymmetry Rate Index for the 24 h period (AR2_24 h)) obtained in the acute stroke phase could be a predictor of a 90 d prognosis. Methods: In this observational study, we recorded and analyzed the 24 h upper limb movement asymmetry of 20 consecutive patients with acute ischemic stroke during their stay in a stroke unit. We recorded the motor activity of both arms using two programmable actigraphic systems positioned on patients’ wrists. We clinically evaluated the stroke patients by NIHSS in the acute phase and then assessed them across 90 days using the modified Rankin Scale (mRS). Results: We found that the AR2_24 h parameter positively correlates with the 90 d mRS (r = 0.69, p < 0.001). Moreover, we found that an AR2_24 h > 32% predicts a poorer outcome (90 d mRS > 2), with sensitivity = 100% and specificity = 89%. Conclusions: Sensor-based parameters might provide useful information for predicting ischemic stroke prognosis in the acute phase.

Neurological disorders are the most devastating and challenging diseases associated with the central nervous system (CNS). The blood-brain barrier (BBB) maintains homeostasis of the brain and contributes towards the maintenance of a very delicate microenvironment, impairing the transport of many therapeutics into the CNS and making the management of common neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), cerebrovascular diseases (CVDs) and traumatic brain injury (TBI), exceptionally complicated. Nanoparticle (NP) technology offers a platform for the design of tissue-specific drug carrying systems owing to its versatile and modifiable nature. The prospect of being able to design NPs capable of successfully crossing the BBB, and maintaining a high drug bioavailability in neural parenchyma, has spurred much interest in the field of nanomedicine. NPs, which also come in an array of forms including polymeric NPs, solid lipid nanoparticles (SLNs), quantum dots and liposomes, have the flexibility of being conjugated with various macromolecules, such as surfactants to confer the physical or chemical property desired. These nanodelivery strategies represent potential novel and minimally invasive approaches to the treatment and diagnosis of these neurological disorders. Most of the strategies revolve around the ability of the NPs to cross the BBB via various influx mechanisms, such as adsorptive-mediated transcytosis (AMT) and receptor-mediated transcytosis (RMT), targeting specific biomarkers or lesions unique to that pathological condition, thereby ensuring high tissue-specific targeting and minimizing off-target side effects. In this article, insights into common neurological disorders and challenges of delivering CNS drugs due to the presence of BBB is provided, before an in-depth review of nanoparticle-based theranostic strategies.

DNA methylation is an epigenetic mechanism by which methyl groups are added to DNA, playing a crucial role in gene expression regulation. The aim of the present study is to compare methylation status of healthy subjects with that of patients with Alzheimer’s, Parkinson’s or Cerebrovascular diseases. We also analyze methylation status of a transgenic Alzheimer’s disease mouse model (3xTg-AD). Our results show that both global methylation (n = 141) and hydroxymethylation (n = 131) levels are reduced in DNA samples from buffy coats of patients with neurodegenerative disorders and age-related cerebrovascular disease. The importance of methylation and hydroxymethylation reduction is stressed by the finding that DNMT3a mRNA levels are also downregulated in buffy coats of patients with Dementia (n = 25). Global methylation is also reduced in brain, liver and serum samples of 3xTg-AD vs. wild type mice, such as DNMT3a mRNA levels that are also decreased in the brain of 3xTg-AD (n = 10). These results suggest that the use of global methylation and hydroxymethylation levels, together with the study of DNMT3a expression, could be useful as a new diagnostic biomarker for these prevalent disorders.

Cognitive impairment and dementia are recognized as major threats to public health. Many studies have shown the important role played by challenges to the cerebral vasculature and the neurovascular unit. To investigate the structural and functional characteristics of the brain, MRI has proven an invaluable tool for visualizing the internal organs of patients and analyzing the parameters related to neuronal activation and blood flow in vivo. Different strategies of imaging can be combined to obtain various parameters: (i) measures of cortical and subcortical structures (cortical thickness, subcortical structures volume); (ii) evaluation of microstructural characteristics of the white matter (fractional anisotropy, mean diffusivity); (iii) neuronal activation and synchronicity to identify functional networks across different regions (functional connectivity between specific regions, graph measures of specific nodes); and (iv) structure of the cerebral vasculature and its efficacy in irrorating the brain (main vessel diameter, cerebral perfusion). The high amount of data obtainable from multi-modal sources calls for methods of advanced analysis, like machine-learning algorithms that allow the discrimination of the most informative features, to comprehensively characterize the cerebrovascular network into specific and sensitive biomarkers. By using the same techniques of human imaging in pre-clinical research, we can also investigate the mechanisms underlying the pathophysiological alterations identified in patients by imaging, with the chance of looking for molecular mechanisms to recover the pathology or hamper its progression.

Background : There is a growing body of evidence suggesting a link between obstructive sleep apnea (OSA) and atrial fibrillation (AF). The primary objective of this study is to evaluate the association between OSA and AF in acute ischemic stroke. The secondary objective is to describe the clinical features of patients with acute ischemic stroke and concomitant OSA. Methods : We enrolled consecutive patients with acute ischemic stroke. All patients underwent full-night cardiorespiratory polygraphy. To determine if there is an association between AF and OSA, we compared the observed frequency of this association with the expected frequency from a random co-occurrence of the two conditions. Subsequently, patients with and without OSA were compared. Results : A total of 174 patients were enrolled (mean age 67.3 ± 11.6 years; 95 males). OSA and AF were present in 89 and 55 patients, respectively. The association OSA + AF was observed in 33/174 cases, which was not statistically different compared to the expected co-occurrence of the two conditions. Patients with OSA showed a higher neck circumference and body mass index, a higher prevalence of hypertension and dysphagia, and a higher number of central apneas/hypoapneas. In the multivariate analysis, dysphagia and hypertension were independent predictors of OSA. A positive correlation was observed between OSA severity, BMI, and neck circumference. The number of central apneas/hypoapneas was positively correlated with stroke severity. Conclusions : Our data suggest that OSA and AF are highly prevalent but not associated in acute stroke. Our findings support the hypothesis that OSA acts as an independent risk factor for stroke.

Cerebral cavernous malformation (CCM) or cavernoma is a major vascular disease of genetic origin, whose main phenotypes occur in the central nervous system, and is currently devoid of pharmacological therapeutic strategies. Cavernomas can remain asymptomatic during a lifetime or manifest with a wide range of symptoms, including recurrent headaches, seizures, strokes, and intracerebral hemorrhages. Loss-of-function mutations in KRIT1/CCM1 are responsible for more than 50% of all familial cases, and have been clearly shown to affect cellular junctions, redox homeostasis, inflammatory responses, and angiogenesis. In this study, we investigated the therapeutic effects of multidrug-loaded lipid nanoemulsions in rescuing the pathological phenotype of CCM disease. The pro-autophagic rapamycin, antioxidant avenanthramide, and antiangiogenic bevacizumab were loaded into nanoemulsions, with the aim of reducing the major molecular dysfunctions associated with cavernomas. Through Western blot analysis of biomarkers in an in vitro CCM model, we demonstrated that drug-loaded lipid nanoemulsions rescue antioxidant responses, reactivate autophagy, and reduce the effect of pro-angiogenic factors better than the free drugs. Our results show the importance of developing a combinatorial preventive and therapeutic approach to reduce the risk of lesion formation and inhibit or completely revert the multiple hallmarks that characterize the pathogenesis and progression of cavernomas.

Acute spontaneous intracerebral hemorrhage (ICH) is the most severe stroke subtype, with a high risk of death, dependence, and dementia. Knowledge about the clinical profile and early outcomes of ICH patients with lobar versus deep subcortical brain topography remains limited. In this study, we investigated the effects of ICH topography on demographics, cerebrovascular risk factors, clinical characteristics, and early outcomes in a sample of 298 consecutive acute ICH patients (165 with lobar and 133 with subcortical hemorrhagic stroke) available in a single-center-based stroke registry over 24 years. The multiple logistic regression analysis shows that variables independently associated with lobar ICH were early seizures (OR 6.81, CI 95% 1.27−5.15), chronic liver disease (OR 4.55, 95% CI 1.03−20.15), hemianopia (OR 2.55, 95% CI 1.26−5.15), headaches (OR 1.90, 95% CI 1.90, 95% IC 1.06−3.41), alcohol abuse (>80 gr/day) (OR 0−10, 95% CI 0.02−0,53), hypertension (OR 0,41, 95% CI 0.23−0−70), sensory deficit (OR 0.43, 95% CI 0.25−0.75), and limb weakness (OR: 0.47, 95% CI 0.24−0.93). The in-hospital mortality was 26.7% for lobar and 16.5% for subcortical ICH. The study confirmed that the clinical spectrum, prognosis, and early mortality of patients with ICH depend on the site of bleeding, with a more severe early prognosis in lobar intracerebral hemorrhage.

Background: Vertigo is an uncommon symptom among acute stroke victims. Knowledge about the clinical profile, the brain location, and the early outcome in stroke patients with cerebrovascular diseases and vertigo remains limited., Objectives: In this study, the effects of vertigo on cerebral topography and early prognosis in cerebrovascular diseases were investigated., Methods: A comparative analysis in terms of demographics, risk factors, clinical characteristics, stroke subtypes, cerebral and vascular topography, and early outcome was performed between patients with presence or absence of vertigo on a sample of 3743 consecutive acute stroke patients available from a 24-year ongoing single-center hospital-based stroke registry., Results: Vertigo was present in 147 patients (3.9%). Multiple logistic regression analysis showed that variables independently associated with vertigo were: location in the cerebellum (OR 5.59, CI 95% 3.24-9.64), nausea or vomiting (OR 4.48, CI 95% 2.95-6.82), medulla (OR 2.87, CI 95% 1.31-6.30), pons (OR 2.39, CI 95% 1.26-4.51), basilar artery (OR 2.36, CI 95% 1.33-4.17), ataxia (OR 2.33, CI 95% 1.41-3.85), and headache (OR 2.31, CI 95% 1.53-3.49)., Conclusion: The study confirmed that the presence of vertigo was not related with increased in-hospital mortality or poor prognosis at hospital discharge. Vertigo is mainly related to non-lacunar vertebrobasilar stroke with topographic localization in the cerebellum and/or brainstem.

Patients with intracranial artery stenosis show high incidence of stroke. Angiography reports contain rich but underutilized information that can enable the detection of cerebrovascular diseases. This study evaluated various natural language processing (NLP) techniques to accurately identify eleven intracranial artery stenosis from angiography reports. Three NLP models, including a rule-based model, a recurrent neural network (RNN), and a contextualized language model, XLNet, were developed and evaluated by internal-external cross-validation. In this study, angiography reports from two independent medical centers (9614 for training and internal validation testing and 315 as external validation) were assessed. The internal testing results showed that XLNet had the best performance, with a receiver operating characteristic curve (AUROC) ranging from 0.97 to 0.99 using eleven targeted arteries. The rule-based model attained an AUROC from 0.92 to 0.96, and the RNN long short-term memory model attained an AUROC from 0.95 to 0.97. The study showed the potential application of NLP techniques such as the XLNet model for the routine and automatic screening of patients with high risk of intracranial artery stenosis using angiography reports. However, the NLP models were investigated based on relatively small sample sizes with very different report writing styles and a prevalence of stenosis case distributions, revealing challenges for model generalization.

The future of healthcare is an organic blend of technology, innovation, and human connection. As artificial intelligence (AI) is gradually becoming a go-to technology in healthcare to improve efficiency and outcomes, we must understand our limitations. We should realize that our goal is not only to provide faster and more efficient care, but also to deliver an integrated solution to ensure that the care is fair and not biased to a group of sub-population. In this context, the field of cardio-cerebrovascular diseases, which encompasses a wide range of conditions-from heart failure to stroke-has made some advances to provide assistive tools to care providers. This article aimed to provide an overall thematic review of recent development focusing on various AI applications in cardio-cerebrovascular diseases to identify gaps and potential areas of improvement. If well designed, technological engines have the potential to improve healthcare access and equitability while reducing overall costs, diagnostic errors, and disparity in a system that affects patients and providers and strives for efficiency.

A high percentage of patients with COVID-19 (coronavirus disease 2019) have previous cardiovascular disease (CVD). The findings presented here came from an epidemiological population-based registry study (real-world data) that enrolled all in-hospital COVID-19 patients with previous CVD from 1 March to 31 May 2020. Death, other comorbidities, hospital stay variables, ventilation type, and main clinical outcomes were evaluated. In Castile and Leon, 35.83% of the 7307 in-hospital COVID-19 patients who participated in this study had previous CVD, particularly arrhythmias (48.97%), cerebrovascular disease (25.02%), ischemic heart disease (22.8%), and chronic heart failure (20.82%). Of the patients, 21.36% were men and more than 90% were over 65 years of age, and the mortality rate achieved 32.93%. The most used medicines were antibiotics (91.41%), antimalarials (73.3%), steroids (46.64%), and antivirals (43.16%). The main predictors of death were age over 65 years (OR: 5), ventilation needs (OR: 2.81), treatment with anti-SIRS (systemic inflammatory response syndrome) medicines (OR: 1.97), antivirals (OR: 1.74) or steroids (OR: 1.68), SIRS (OR: 5.75), SARS (severe acute respiratory syndrome) (OR: 2.44), or AKI (acute kidney injury) (OR: 1.63) occurrence. Chronic heart failure and cerebrovascular disease were associated with a worse clinical course of COVID-19, especially in men older than 65 years with diabetes who developed SIRS, SARS, or AKI.

Background: The combined use of clopidogrel and aspirin is recommended for the short-term (21 days) therapy of minor stroke or transient ischemic attack. Previous studies have demonstrated its efficacy and superiority over treatment with a single antiplatelet agent. However, there is insufficient support for the advantages of such therapy based on platelet function testing. We aimed to compare the effect of the concomitant use of clopidogrel and aspirin versus clopidogrel alone on the dynamics of platelet reactivity over time to determine the appropriate antiplatelet treatment strategy for minor strokes., Methods: We enrolled 74 ischemic stroke subjects, including 38 minor strokes. Platelet reactivity was assessed by impedance aggregometry (Multiplate Analyzer) 48 and 96 h after a first 75 mg dose of clopidogrel, using the acetylsalicylic acid platelet inhibition (ASPI) test and the adenosine diphosphate (ADP) test. Dual antiplatelet therapy was strictly reserved only to minor strokes, as the other strokes received clopidogrel alone in the secondary prevention. The dynamics of platelet reactivity refer to the difference between two assessments, and a decrease in values over time was considered favorable., Results: The incidence of clopidogrel non-responsiveness was 64.8%, and this was similar in the group of minor strokes and the group of more disabling strokes. We indicated diabetes mellitus as an independent predictor of high on-clopidogrel platelet reactivity (Odds ratio OR 5.69 95% Confidence Interval CI 1.13-41.26, p = 0.0386). Among minor strokes treated with dual antiplatelet therapy, in relation to clopidogrel, we reported a trend toward more favorable dynamics of platelet reactivity over time compared to the group using clopidogrel alone ( p = 0.0652 vs. p = 0.3384, respectively). We identified five predictors (sex, female; small-vessel disease; no diabetes; no hyperlipidemia; and no alcohol abuse) related to a significant decrease in platelet reactivity over time with respect to clopidogrel. No significant dynamics of platelet reactivity when using aspirin were found., Conclusions: Our findings, based on the favorable dynamics of platelet reactivity over time in relation to clopidogrel, confirm the usefulness of dual antiplatelet therapy in minor strokes and support the continuation of the secondary prevention with clopidogrel alone rather than aspirin, particularly among identified beneficiaries of such a strategy.