Molecular Mechanisms and Pathophysiology of Acute Stroke: Recent Advances and Controversies.

Stroke is a prevalent neurological disorder defined as an abnormality in brain function resulting from the disruption of cerebral circulation [...].

Predictive Clinical Factors of In-Hospital Mortality in Women Aged 85 Years or More with Acute Ischemic Stroke.

INTRODUCTION: There are limited data on the outcome of acute ischemic stroke oldest old women. We assessed clinical risk factors for in-hospital mortality in women aged 85 years or more with acute ischemic stroke. METHODS: This single-center retrospective cohort study included 506 women aged ≥ 85 years collected from a total of 4,600 patients with acute cerebral infarction registered in an ongoing 24-year hospital stroke database. The identification of clinical risk factors for in-hospital mortality was the primary endpoint of the study. RESULTS: The mean (± standard deviation) age of the patients was 88.6 ± 3.2 years. Stroke subtypes were cardioembolic infarcts in 37.7% of patients, atherothrombotic infarcts in 30.8%, infarcts of unknown cause and lacunar infarcts in 26.1% each, and infarcts of unusual cause in 11.5%. The in-hospital mortality rate was 20.4% (n = 103). Cardioembolic infarct accounted for 67% of all deaths (n = 69). Sudden stroke onset (OR 1.87, 95% CI 1.14-3.06), altered consciousness (OR 7.05, 95% CI 4.36-11.38) and neurological, cardiac, respiratory, and hemorrhagic events during hospitalization were independent risk factors for death, whereas lacunar infarction was a protective factor (OR 0.10, 95% CI 0.01-0.82). CONCLUSION: The oldest old age segment of women with acute ischemic infarction is a subgroup of stroke patients with unfavorable prognosis and high in-hospital mortality associated with sudden stroke onset, altered consciousness and medical complications developed during hospitalization. Lacunar infarction as stroke subtype showed a favourable prognosis.

Gender Predicts Differences in Acute Ischemic Cardioembolic Stroke Profile: Emphasis on Woman-Specific Clinical Data and Early Outcome-The Experience of Sagrat Cor Hospital of Barcelona Stroke Registry.

Background and Objectives: Acute ischemic cardioembolic stroke (CS) is a clinical condition with a high risk of death, and can lead to dependence, recurrence, and dementia. Materials and Methods: In this study, we evaluated gender differences and female-specific clinical data and early outcomes in 602 women diagnosed with CS from a total of 4600 consecutive acute stroke patients in a single-center hospital stroke registry over 24 years. A comparative analysis was performed in women and men in terms of demographics, cerebrovascular risk factors, clinical data, and early outcomes. Results: In a multivariate analysis, age, hypertension, valvular heart disease, obesity, and internal capsule location were independent variables associated with CS in women. The overall in-hospital mortality rate was similar, but the group of women had a greater presence of neurological deficits and a higher percentage of severe limitation at hospital discharge. After the multivariate analysis, age, altered consciousness, limb weakness, and neurological, respiratory, gastrointestinal, renal, cardiac and peripheral vascular complications were independent predictors related to early mortality in women. Conclusions: Women with CS showed a differential demographic and clinical profile and worse early outcomes than men. Advanced age, impaired consciousness, and medical complications were predictors of stroke severity in women with CS.

Molecular Mechanisms and Pathophysiology of Acute Stroke: Emphasis on Biomarkers in the Different Stroke Subtypes.

According to WHO data, strokes are the second leading cause of death in adult males, the first cause of death of adult women worldwide and one of the most important causes of disability and dementia in adults [...].

The Potential Impact of Neuroimaging and Translational Research on the Clinical Management of Lacunar Stroke.

Lacunar infarcts represent one of the most frequent subtypes of ischemic strokes and may represent the first recognizable manifestation of a progressive disease of the small perforating arteries, capillaries, and venules of the brain, defined as cerebral small vessel disease. The pathophysiological mechanisms leading to a perforating artery occlusion are multiple and still not completely defined, due to spatial resolution issues in neuroimaging, sparsity of pathological studies, and lack of valid experimental models. Recent advances in the endovascular treatment of large vessel occlusion may have diverted attention from the management of patients with small vessel occlusions, often excluded from clinical trials of acute therapy and secondary prevention. However, patients with a lacunar stroke benefit from early diagnosis, reperfusion therapy, and secondary prevention measures. In addition, there are new developments in the knowledge of this entity that suggest potential benefits of thrombolysis in an extended time window in selected patients, as well as novel therapeutic approaches targeting different pathophysiological mechanisms involved in small vessel disease. This review offers a comprehensive update in lacunar stroke pathophysiology and clinical perspective for managing lacunar strokes, in light of the latest insights from imaging and translational studies.

Contribution of "Omic" Studies to the Understanding of Cadasil. A Systematic Review.

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a small vessel disease caused by mutations in NOTCH3 that lead to an odd number of cysteines in the epidermal growth factor (EGF)-like repeat domain, causing protein misfolding and aggregation. The main symptoms are migraines, psychiatric disorders, recurrent strokes, and dementia. Omic technologies allow the massive study of different molecules for understanding diseases in a non-biased manner or even for discovering targets and their possible treatments. We analyzed the progress in understanding CADASIL that has been made possible by omics sciences. For this purpose, we included studies that focused on CADASIL and used omics techniques, searching bibliographic resources, such as PubMed. We excluded studies with other phenotypes, such as migraine or leukodystrophies. A total of 18 articles were reviewed. Due to the high prevalence of NOTCH3 mutations considered pathogenic to date in genomic repositories, one can ask whether all of them produce CADASIL, different degrees of the disease, or whether they are just a risk factor for small vessel disease. Besides, proteomics and transcriptomics studies found that the molecules that are significantly altered in CADASIL are mainly related to cell adhesion, the cytoskeleton or extracellular matrix components, misfolding control, autophagia, angiogenesis, or the transforming growth factor ß (TGFß) signaling pathway. The omics studies performed on CADASIL have been useful for understanding the biological mechanisms and could be key factors for finding potential drug targets.

Cardioembolic Stroke: Risk Factors, Clinical Features, and Early Outcome in 956 Consecutive Patients.

BACKGROUND: There is little information about the early clinical features of cardioembolic stroke before complementary examinations. OBJECTIVE: The aim of this study was to identify risk factors, clinical features, and early outcomes of cardioembolic stroke. METHODS: Retrospective study based on prospectively collected data available from a university medical center hospitalbased stroke registry. Consecutive patients diagnosed with cardioembolic infarction were selected and compared to those diagnosed with an atherothrombotic stroke. Predictors of cardioembolic infarction were assessed by multivariate analysis. RESULTS: From a cohort of 4597 consecutive patients, we studied 956 patients diagnosed with cardioembolic infarction (80 years [standard deviation (SD) 9.14]; 63% women) and 945 with atherothrombotic infarction (77.01 years [SD 9.75]; 49.8% women). The univariate comparative analysis reported that advanced age (≥ 85 years), female gender, atrial fibrillation (AF), ischemic heart disease, and congestive heart failure were significantly more frequent in the cardioembolic group, whereas hypertension, diabetes, peripheral vascular disease, heavy smoking, hyperlipidemia, and previous transient ischemic attack were significant in the atherothrombotic group. In the logistic regression model, AF (odds ratio [OR] 15.75, 95% confidence interval [CI]: 12.14-20.42), ischemic heart disease (OR 3.12, 95% CI: 2.16-4.5), female gender (OR 1.56, 95% CI: 1.22-2.00), and sudden-onset (OR 1.97, 95% CI: 1.54-2.51), were independent significant predictors of cardioembolic stroke. CONCLUSIONS: Potential cardioembolic stroke requires a comprehensive evaluation, since early classification and identification through predictors would improve effective management.

GRECOS Project (Genotyping Recurrence Risk of Stroke): The Use of Genetics to Predict the Vascular Recurrence After Stroke.

BACKGROUND AND PURPOSE: Vascular recurrence occurs in 11% of patients during the first year after ischemic stroke (IS) or transient ischemic attack. Clinical scores do not predict the whole vascular recurrence risk; therefore, we aimed to find genetic variants associated with recurrence that might improve the clinical predictive models in IS. METHODS: We analyzed 256 polymorphisms from 115 candidate genes in 3 patient cohorts comprising 4482 IS or transient ischemic attack patients. The discovery cohort was prospectively recruited and included 1494 patients, 6.2% of them developed a new IS during the first year of follow-up. Replication analysis was performed in 2988 patients using SNPlex or HumanOmni1-Quad technology. We generated a predictive model using Cox regression (GRECOS score [Genotyping Reurrence Risk of Stroke]) and generated risk groups using a classification tree method. RESULTS: The analyses revealed that rs1800801 in the MGP gene (hazard ratio, 1.33; P=9×10-03), a gene related to artery calcification, was associated with new IS during the first year of follow-up. This polymorphism was replicated in a Spanish cohort (n=1.305); however, it was not significantly associated in a North American cohort (n=1.683). The GRECOS score predicted new IS (P=3.2×10-09) and could classify patients, from low risk of stroke recurrence (1.9%) to high risk (12.6%). Moreover, the addition of genetic risk factors to the GRECOS score improves the prediction compared with previous Stroke Prognosis Instrument-II score (P=0.03). CONCLUSIONS: The use of genetics could be useful to estimate vascular recurrence risk after IS. Genetic variability in the MGP gene was associated with vascular recurrence in the Spanish population.

Efficacy of continuous positive airway pressure treatment on 5-year survival in patients with ischaemic stroke and obstructive sleep apnea: a randomized controlled trial.

The main purpose of the present analysis is to assess the influence of introducing early nasal continuous positive airway pressure (nCPAP) treatment on cardiovascular recurrences and mortality in patients with a first-ever ischaemic stroke and moderate-severe obstructive sleep apnea (OSA) with an apnea-hypopnea index (AHI) ≥20 events h(-1) during a 5-year follow-up. Patients received conventional treatment for stroke and were assigned randomly to the nCPAP group (n = 71) or the control group (n = 69). Cardiovascular events and mortality were registered for all patients. Survival and cardiovascular event-free survival analysis were performed after 5-year follow-up using the Kaplan-Meier test. Patients in the nCPAP group had significantly higher cardiovascular survival than the control group (100 versus 89.9%, log-rank test 5.887; P = 0.015) However, and also despite a positive tendency, there were no significant differences in the cardiovascular event-free survival at 68 months between the nCPAP and control groups (89.5 versus 75.4%, log-rank test 3.565; P = 0.059). Early nCPAP therapy has a positive effect on long-term survival in ischaemic stroke patients and moderate-severe OSA.

Malignant middle cerebral artery infarction: a clinical study of 32 patients.

BACKGROUND AND OBJECTIVE: Malignant middle cerebral artery infarction is a devastating type of ischemic stroke whose clinical predictors remain scarcely known. The present study aims to improve the knowledge about the prognosis factors through an analysis of a malignant middle cerebral artery infarction sample of patients from our stroke registry. MATERIAL AND METHODS: From a total of 1,396 patients with ischemic stroke in the middle cerebral artery included in the "Sagrat Cor Hospital of Barcelona Stroke Registry", we identified 32 patients with malignant middle cerebral artery infarction (2.3%). Demographic, anamnestic, clinical, and outcome variables in this subgroup of patients were compared with those of the middle cerebral artery. The independent predictive value of each variable on the development of malignant middle cerebral artery infarction was assessed with a logistic regression analysis. RESULTS: The mean age was 74.7 (SD, 11.4) years and 50% were males. In-hospital death was observed in eight patients (25%) and early bad prognosis (in-hospital death or severe residual focality at discharge) was present in 16 patients (50%). Decreased consciousness (OR: 4.17; 95% CI: 2.02-8.61), presence of nausea or vomiting (OR: 3.65; 95% CI: 1.40-8.49), and heavy smoking (> 20 cigarettes/day; OR: 2.62; 95% CI: 1.03-6.64) appeared to be independent prognostic factors for malignant middle cerebral artery infarction in the multivariate analysis. CONCLUSIONS: Malignant middle cerebral artery infarction is an infrequent clinical condition associated with poor prognosis and high mortality rate. In our sample, decreased consciousness, nausea or vomiting, and heavy smoking are the main clinical factors associated.

Cognitive profile in patients with a first-ever lacunar infarct with and without silent lacunes: a comparative study.

BACKGROUND: The detection of early neuropsychological abnormalities as precursors of cognitive decline of vascular origin in patients with lacunar stroke is a subject of increasing interest. The objective of this study was to assess whether there were differences in the performance of a battery of neuropsychological tests in first-ever lacunar stroke patients with and without associated silent multiple lacunar infarctions found incidentally on the brain magnetic resonance imaging (MRI) scan. METHODS: A total of 72 consecutive patients with first-ever lacunar infarction were studied 1 month after stroke. All patients underwent a comprehensive neuropsychological evaluation, which included the California Verbal Learning Test (CVLT), Phonetic Verbal Fluency Test (PMR), Semantic Verbal Fluency Test (category "animals"), Digit Span Forward and Backward from the Wechsler Adult Intelligence Scale (WAIS-III), and Mini-Mental State Examination (MMSE). RESULTS: A total of 38 patients (52.7%) had silent multiple lacunar infarcts, with corona radiata as the most frequent topography (P < 0.023). White matter hyperintensities (leukoaraiosis) were observed in 81.1% of patients with silent multiple lacunar infarcts and in 50% with a single lacunar infarction (P < 0.007). Patients in both groups showed similar scores in the MMSE, but those with associated silent lacunar infarctions showed a poorer performance in the semantic fluency test (P < 0.008) and in short delayed verbal memory (P < 0.001). In both cases, however, leukoaraiosis was not statistically significant in multivariate linear regression models adjusted by confounding covariates. In these models, multiple silent lacunar infarctions and education were independent predictors of poor performance in the semantic fluency test and in short delayed verbal memory. CONCLUSIONS: The presence of silent multiple lacunar infarctions documented on brain MRI scans in patients with first-ever lacunar stroke was associated with mild neuropsychological abnormalities, particularly in the performance of executive functions (semantic fluency) and short delayed verbal memory. According to these findings, in the initial stages of small vessel disease, mild neuropsychological abnormalities appear to be related to lacunes rather than to leukoaraiosis or perivascular hyperintensities of vascular cause.

Acute Spontaneous Lobar Cerebral Hemorrhages Present a Different Clinical Profile and a More Severe Early Prognosis than Deep Subcortical Intracerebral Hemorrhages-A Hospital-Based Stroke Registry Study.

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.

Trends in clinical features and early outcome in patients with acute cardioembolic stroke subtype over a 19-year period.

OBJECTIVES: To assess changing trends in clinical characteristics and early outcome of patients with acute cardioembolic stroke (ACS) over a 19-year period. MATERIALS AND METHODS: Data of 575 patients with first-ever ACS included in the Sagrat Cor Hospital of Barcelona Stroke Registry were analyzed. Changing trends for 1986-1992, 1993-1998, and 1999-2004 periods were compared. RESULTS: A statistically significant increase (P < 0.001) in the age of patients (74.6 years in 1986-1992 vs. 81.4 years in 1999-2004) and the percentage of patients older than 85 years of age (16% vs. 38.2%) was observed. Patients with hypertension increased from 40.5 to 60.8% (P = 0.001) as were patients with diabetes, chronic bronchitis, and obesity (P = NS). The median length of hospital stay decreased from 18 to 12 days (P = 0.031) and prolonged hospital stay (>12 days) from 18.3 to 13.1 (P = 0.033). In-hospital death rate remained around 20%. CONCLUSIONS: ACS continues to be a severe ischemic stroke subtype with high risk of in-hospital death. The lack of improvement in the early prognosis over a 19-year period may be explained by an increase in the prevalence of major cardiovascular risk factors and progressive aging of the population.

Relationship between Performance and Inter-Limb Asymmetries Using Flywheel Resistance Device in Elite Youth Female Basketball Players.

The purposes of this study were to quantify inter-limb asymmetries from unilateral jumps, change of direction (COD) speed, and flywheel resistance skill tests and to examine their relationship with physical performance in a sample of elite youth female basketball players. Eleven female basketball players (age = 17.56 ± 0.60 year; body mass = 75.13 ± 12.37 kg; height = 1.83 ± 0.08 m; BMI = 22.42 ± 2.28; sports experience = 6.31 ± 1.73 year; years post-peak height velocity = 4.79 ± 0.68 year) performed a battery of fitness tests in the post-season consisting of the Single Leg Countermovement Jump in vertical (SLCJ-V), horizontal (SLCJ-H), and lateral (SLCJ-L) directions, 135° and 90° COD tests, and four skills (acceleration step, deceleration step, sidestep, and crossover step) with an flywheel resistance device. The results showed significant differences between the higher performing and lower performing limbs across all tasks (p < 0.05). The mean asymmetry index values ranged from 1.26% (COD 135°) to 11.75% (SLC-V). Inter-limb asymmetries were greatest during the flywheel resistance skills. Spearman's correlations (ρ) for all tests were only significant for inter-limb asymmetries during the sidestep test and reduced performance in SLCJ-L (ρ = −0.61; p = 0.046) and all COD deficits (ρ range = −0.72 to −0.81). The findings of the present study showed that inter-limb asymmetries are task-specific in female youth basketball players and suggest that the use of flywheel devices can be included in the battery of tests to detect inter-limb asymmetry.

Vertigo in Acute Stroke Is a Predictor of Brain Location but Is Not Related to Early Outcome: The Experience of Sagrat Cor Hospital of Barcelona Stroke Registry.

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.

Patent foramen ovale closure in non-lacunar cryptogenic ischemic stroke: where are we now?

Patent foram ovale (PFO) is the most common anatomical cause of an interarterial shunt. It is usually asymptomatic but may cause paradoxical embolism and is a risk factor for non-lacunar cryptogenic cerebral ischemia in young adults. Although the first clinical trials did not show a significant superiority of PFO closure in the secondary prevention of cerebral ischemia as compared with standard antithrombotic treatment, six subsequent randomized clinical trials (CLOSURE I, PC Trial, RESPECT, CLOSE, REDUCE, and DEFENSE-PFO) performed in a sample of cryptogenic stroke in patients aged 60 years or younger provided evidence of a significant reduction of recurrent cerebral ischemia after percutaneous PFO closure. However, the use of percutaneous PFO closure cannot be generalized to the entire population of patients with cerebral ischemia and PFO, but it is indicated in highly selected patients with non-lacunar cryptogenic cerebral infarction with a large right-to-left shunt, an atrial septal aneurysm and no evidence of atrial fibrillation, as well as in association with antithrombotic treatment for an optimal secondary prevention of cerebral ischemia.

The Behaviour of Home Advantage during the COVID-19 Pandemic in European Rink Hockey Leagues.

The primary purpose of the present study was to compare the home advantage (HA) and the home team performance in the most relevant European rink hockey leagues (Spanish, Portuguese and Italian), considering the presence or absence of spectators in the competition venues due to the effect of COVID-19 restrictions. The sample was composed of 1665 rink hockey matches (654 from the Spanish league, 497 from the Portuguese league, and 514 from the Italian league) played between the 2018-2019 and 2020-2021 seasons. The HA and match variables comparisons were established using several negative binomial regression models. Results showed that the effect of HA did not disappear despite playing without spectators but decreased from 63.99% to 57.41% (p = 0.002). Moreover, the comparison of the match variables showed that playing with spectators benefited local teams' performance, especially in the Portuguese and Italian leagues. Playing with spectators favoured local team performance in rink hockey matches, which is more evident in some analysed leagues. However, as HA does not disappear entirely without spectators, it is necessary to study other relevant performance factors that are not directly or indirectly attributable to crowd behaviour in rink hockey performance analyses.

Differential Characteristics of Ischemic and Hemorrhagic Stroke in Patients with Cerebral Small Vessel Disease.

BACKGROUND: Small vessel disease (SVD) is the underlying anatomical substrate for both lacunar infarction and subcortical hemorrhage. AIM: To assess predictive factors of ischemic or hemorrhagic stroke in patients with cerebral SVD. MATERIALS AND METHODS: Prospective hospital-based stroke registry ("The Sagrat Cor Hospital of Barcelona Stroke Registry") in an acute-care teaching hospital in Barcelona, Spain. From 4597 acute stroke patients included in the stroke registry over a 24-year period, 440 cases of lacunar stroke and 210 of subcortical intracerebral hemorrhage were selected. Demographics, clinical characteristics, risk factors, and early outcome were compared. Predictors of lacuna versus subcortical hemorrhage were assessed by multivariate analyses. RESULTS: In a logistic regression model based on demographics, risk factors, clinical features and outcome, dyslipidemia (odds ratio [OR] 2.06 (95% confidence interval (CI) 1.17-3.62) and diabetes (OR 1.97, 95% CI 1.19-3.26) were independent risk factors for lacunar infarction. Anticoagulation therapy (OR 0.05, 95% CI 0.01-0.28), sudden onset (OR 0.51, 95% CI 0.33-0.78), motor symptoms (OR 0.44, 95% CI 0.26-0.76), headache (OR 0.23, 95% CI 0.12-0.41), altered consciousness (OR 0.10, 95% CI 0.05-0.21), respiratory complications (OR 0.19, 95% CI 0.08-0.46), and in-hospital death (OR 0.08, 95% CI 0.02-0.36) were predictors of subcortical hemorrhage. CONCLUSION: Identification of differential clinical and prognostic profile between ischemic and hemorrhagic consequences of underlying cerebral SVD is useful for risk stratification in the current process pursuing precision medicine.