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Haemorrhagic transformation (HT) of ischaemic infarction occurs when an area of brain infarction is stained with blood products, mainly red blood cells. An abnormally permeable blood–brain barrier resulting from ischaemia of the capillary endothelium allows this extravasation of blood products. HT is part of the natural history of some forms of ischaemic infarction, especially cerebral embolism, but it can be precipitated or enhanced by therapeutic interventions used in the acute phase of ischaemic stroke. The old view of HT after cerebral embolism as a generally asymptomatic change in a tissue that is already necrotic has been challenged by observations from therapeutic thrombolysis that suggest that HT can have a negative effect on patients' outcomes. Understanding of the risk factors for and the underlying mechanisms and clinical variability of HT in the context of acute therapeutic interventions in ischaemic stroke could help in the early detection of this complication, in determining the safety of recanalisation approaches, and in setting the stage for future research into the prevention or treatment of HT in patients with acute ischaemic stroke.

Background Silent brain infarcts are detected by neuroimaging in up to 20% of asymptomatic patients based on population studies. They are five times more frequent than stroke in general population, and increase significantly both with advancing age and hypertension. Moreover, they are independently associated with the risk of future stroke and cognitive decline. Despite these numbers and the clinical consequences of silent brain infarcts, their prevalence in Mediterranean populations is not well known and their role as predictors of future cerebrovascular and cardiovascular events in hypertensive remains to be determined. ISSYS (Investigating Silent Strokes in Hypertensives: a magnetic resonance imaging study) is an observational cross-sectional and longitudinal study aimed to: 1- determine the prevalence of silent cerebrovascular infarcts in a large cohort of 1000 hypertensives and to study their associated factors and 2-to study their relationship with the risk of future stroke and cognitive decline. Methods/Design Cohort study in a randomly selected sample of 1000 participants, hypertensive aged 50 to 70 years old, with no history of previous stroke or dementia. On baseline all participants will undergo a brain MRI to determine the presence of brain infarcts and other cerebrovascular lesions (brain microbleeds, white matter changes and enlarged perivascular spaces) and will be also tested to determine other than brain organ damage (heart-left ventricular hypertrophy, kidney-urine albumin to creatinine ratio, vessels-pulse wave velocity, ankle brachial index), in order to establish the contribution of other subclinical conditions to the risk of further vascular events. Several sub-studies assessing the role of 24 hour ambulatory BP monitoring and plasma or genetic biomarkers will be performed. Follow-up will last for at least 3 years, to assess the rate of further stroke/transient ischemic attack, other cardiovascular events and cognitive decline, and their predictors. Discussion Improving the knowledge on the frequency and determinants of these lesions in our setting might help in the future to optimize treatments or establish new preventive strategies to minimize clinical and socioeconomic consequences of stroke and cognitive decline.

BackgroundIn addition to other stroke-related deficits, the risk of seizures may impact driving ability after stroke.MethodsWe analysed data from a multicentre international cohort, including 4452 adults with acute ischaemic stroke and no prior seizures. We calculated the Chance of Occurrence of Seizure in the next Year (COSY) according to the SeLECT2.0 prognostic model. We considered COSY<20% safe for private and <2% for professional driving, aligning with commonly used cut-offs.ResultsSeizure risks in the next year were mainly influenced by the baseline risk-stratified according to the SeLECT2.0 score and, to a lesser extent, by the poststroke seizure-free interval (SFI). Those without acute symptomatic seizures (SeLECT2.0 0–6 points) had low COSY (0.7%–11%) immediately after stroke, not requiring an SFI. In stroke survivors with acute symptomatic seizures (SeLECT2.0 3–13 points), COSY after a 3-month SFI ranged from 2% to 92%, showing substantial interindividual variability. Stroke survivors with acute symptomatic status epilepticus (SeLECT2.0 7–13 points) had the highest risk (14%–92%).ConclusionsPersonalised prognostic models, such as SeLECT2.0, may offer better guidance for poststroke driving decisions than generic SFIs. Our findings provide practical tools, including a smartphone-based or web-based application, to assess seizure risks and determine appropriate SFIs for safe driving.

Early-onset and late-onset Alzheimer’s disease (EOAD and LOAD) are two forms of the disease with the same characteristic neuropathological hallmarks. However, higher burdens of neuritic plaques and neurofibrillary tangles in frontal and parietal lobes have been found in EOAD than in LOAD patients. Thus, the EOAD subjects may have a differentiated clinical presentation compared to the LOAD ones. Some authors have found less hippocampal memory presentations and more focal cortical abnormalities (such as visuoconstructive or executive dysfunction) in EOAD than LOAD patients. The aim of the present study was to determine which initial clinical profiles differ between EOAD and LOAD; and to analyze whether another age cut-off could discriminate better between EOAD and LOAD clinical presentations than the conventional limit of 65. All patients fulfilling NINCDS-ADRDA criteria for probable Alzheimer’s disease who referred to our Hospital between October 2007 and December 2012 were included in the study. The conventional age limit of 65 was established to distinguish between EOAD and LOAD. Baseline neuropsychological scores, adjusted for age and education, were compared between both groups. A total of 181 patients (38 EOAD, 143 LOAD) entered in the analysis. Sex distribution and time of evolution of symptoms did not differ between groups. The EOAD patients performed worse than LOAD in attentional, imitation praxis and verbal learning tests. In addition, the age cut-off of 70 was found to differentiate between early- and late-onset groups better than the standard cut-off of 65 years old. Our results support a differentiated neuropsychological impairment pattern in EOAD compared to LOAD.

Stroke is a major cause of disability and death globally, and prediction of mortality represents a crucial challenge. We aimed to identify blood biomarkers measured during acute ischemic stroke that could predict long-term mortality. Nine hundred and forty-one ischemic stroke patients were prospectively recruited in the Stroke-Chip study. Post-stroke mortality was evaluated during a median 4.8-year follow-up. A 14-biomarker panel was analyzed by immunoassays in blood samples obtained at hospital admission. Biomarkers were normalized and standardized using Z-scores. Multiple Cox regression models were used to identify clinical variables and biomarkers independently associated with long-term mortality and mortality due to stroke. In the multivariate analysis, the independent predictors of long-term mortality were age, female sex, hypertension, glycemia, and baseline National Institutes of Health Stroke Scale (NIHSS) score. Independent blood biomarkers predictive of long-term mortality were endostatin > quartile 2, tumor necrosis factor receptor-1 (TNF-R1) > quartile 2, and interleukin (IL)-6 > quartile 2. The risk of mortality when these three biomarkers were combined increased up to 69%. The addition of the biomarkers to clinical predictors improved the discrimination (integrative discriminative improvement (IDI) 0.022 (0.007–0.048), p < 0.001). Moreover, endostatin > quartile 3 was an independent predictor of mortality due to stroke. Altogether, endostatin, TNF-R1, and IL-6 circulating levels may aid in long-term mortality prediction after stroke.

Advances in acute stroke therapy resulting from thrombolytic treatment, endovascular procedures, and stroke units have improved significantly stroke survival and prognosis; however, for the large majority of patients lacking access to advanced therapies stroke mortality and residual morbidity remain high and many patients become incapacitated by motor and cognitive deficits, with loss of independence in activities of daily living. Therefore, over the past several years, research has been directed to limit the brain lesions produced by acute ischemia (neuroprotection) and to increase the recovery, plasticity and neuroregenerative processes that complement rehabilitation and enhance the possibility of recovery and return to normal functions (neurorepair). Citicoline has therapeutic effects at several stages of the ischemic cascade in acute ischemic stroke and has demonstrated efficiency in a multiplicity of animal models of acute stroke. Long-term treatment with citicoline is safe and effective, improving post-stroke cognitive decline and enhancing patients’ functional recovery. Prolonged citicoline administration at optimal doses has been demonstrated to be remarkably well tolerated and to enhance endogenous mechanisms of neurogenesis and neurorepair contributing to physical therapy and rehabilitation.

Arterial recanalization and subsequent reperfusion have extensively demonstrated the ability to restore the brain function when performed shortly after acute ischemic stroke. Experimental and human studies have consistently demonstrated that early tissue reperfusion may limit ischemic tissue enlargement, leading to a reduced infarct size and favorable clinical outcome. However, arterial recanalization does not necessarily lead to brain tissue reperfusion. Lack of reperfusion after early recanalization may be caused by multiple downstream embolization, blockage of microcirculation due to non-reflow phenomenon or rapid recruitment of ischemic tissue before recanalization resulting in non-nutritional reperfusion. In some cases, sudden tissue reperfusion may be deleterious, leading to brain blood barrier disruption and hemorrhagic transformation or massive brain edema due to the so-called ‘reperfusion injury’. In spite of this, recanalization represents the powerful predictor of stroke outcome and it is being increasingly used as a surrogate efficacy measurement in thrombolytic and other revascularization trials in acute stroke. Several emerging strategies have the potential to extend cerebral reperfusion therapy to larger numbers of patients, including patients presenting beyond the current 3-hour time window. Moreover, novel reperfusion approaches may improve the efficacy and safety of thrombolysis in a larger number of stroke patients. This review highlights recent advances in reperfusion treatments for acute ischemic stroke.

Stroke is one of the most common causes of death and disability. Reperfusion therapies are the only treatment available during the acute phase of stroke. Due to recent clinical trials, these therapies may increase their frequency of use by extending the time-window administration, which may lead to an increase in complications such as hemorrhagic transformation, with parenchymal hematoma (PH) being the more severe subtype, associated with higher mortality and disability rates. Our aim was to find genetic risk factors associated with PH, as that could provide molecular targets/pathways for their prevention/treatment and study its genetic correlations to find traits sharing genetic background. We performed a GWAS and meta-analysis, following standard quality controls and association analysis (fastGWAS), adjusting age, NIHSS, and principal components. FUMA was used to annotate, prioritize, visualize, and interpret the meta-analysis results. The total number of patients in the meta-analysis was 2034 (216 cases and 1818 controls). We found rs79770152 having a genome-wide significant association (beta 0.09, p-value 3.90 × 10−8) located in the RP11-362K2.2:RP11-767I20.1 gene and a suggestive variant (rs13297983: beta 0.07, p-value 6.10 × 10−8) located in PCSK5 associated with PH occurrence. The genetic correlation showed a shared genetic background of PH with Alzheimer’s disease and white matter hyperintensities. In addition, genes containing the ten most significant associations have been related to aggregated amyloid-β, tau protein, white matter microstructure, inflammation, and matrix metalloproteinases.

Background and purpose Infarct volume and age are strong predictors of outcome in patients with stroke. We aimed to determine the impact of infarct volume on outcome according to age. Methods Consecutive patients with acute stroke with documented internal carotid artery/middle cerebral artery occlusion who underwent endovascular procedures were studied. Patients were categorized in three age groups: <70 years (G1), 70–79 years (G2), ≥80 years (G3). The Alberta Stroke Program Early CT score (ASPECTS) was graded on initial CT. Time of successful recanalization (Thrombolysis In Cerebral Infarct (TICI) ≥2b )and good outcome at 3 months (modified Rankin Scale score ≤2) were recorded. Infarct volume was measured on the 24 h control CT. Results A total of 214 patients were studied (G1: 68; G2: 74; G3: 72). For all patients the mean infarct volume was 94.7±127 mL; 35.6% had a good outcome. We observed larger infarct volumes in patients with a bad outcome in each age group (G1: 22 vs 182 mL, p<0.01/G2: 22 vs 164 mL, p<0.01/G3: 7.6 vs 132 mL, p<0.01). However, the target cut-off infarct volume that better predicted a good outcome decreased as age increased: G1: 49 mL (sensitivity 80%, specificity 92.6%); G2: 32.5 mL (sensitivity 80%, specificity 81%); G3: 15.2 mL (sensitivity 81.3%, specificity 86.7%). Overall, after adjusting for age, occlusion location, baseline NIH Stroke Scale score and infarct volume, the only predictor of a good outcome was achieving a final infarct volume less than the age-adjusted target (OR 5.5, 95% CI 1.6 to 18.8; p<0.01). The probability of achieving an infarct volume less than the age-adjusted target decreased according to baseline ASPECTS, time and degree of recanalization. Conclusions Age-adjusted infarct size might represent a powerful surrogate marker of stroke outcome and further refine the predictive accuracy of infarct volume on prognosis in patients with stroke undergoing endovascular treatment. This information may be used in the design of new trials to individualize selection criteria for different age groups.

Background Many guidelines recommend urgent intervention for patients with two or more transient ischaemic attacks (TIAs) within 7 days (multiple TIAs) to reduce the early risk of stroke. Objective To determine whether all patients with multiple TIAs have the same high early risk of stroke. Methods Between April 2008 and December 2009, we included 1255 consecutive patients with a TIA from 30 Spanish stroke centres (PROMAPA study). We prospectively recorded clinical characteristics. We also determined the short-term risk of stroke (at 7 and 90 days). Aetiology was categorised using the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Results Clinical variables and extracranial vascular imaging were available and assessed in 1137/1255 (90.6%) patients. 7-Day and 90-day stroke risk were 2.6% and 3.8%, respectively. Large-artery atherosclerosis (LAA) was confirmed in 190 (16.7%) patients. Multiple TIAs were seen in 274 (24.1%) patients. Duration <1 h (OR=2.97, 95% CI 2.20 to 4.01, p<0.001), LAA (OR=1.92, 95% CI 1.35 to 2.72, p<0.001) and motor weakness (OR=1.37, 95% CI 1.03 to 1.81, p=0.031) were independent predictors of multiple TIAs. The subsequent risk of stroke in these patients at 7 and 90 days was significantly higher than the risk after a single TIA (5.9% vs 1.5%, p<0.001 and 6.8% vs 3.0%, respectively). In the logistic regression model, among patients with multiple TIAs, no variables remained as independent predictors of stroke recurrence. Conclusions According to our results, multiple TIAs within 7 days are associated with a greater subsequent risk of stroke than after a single TIA. Nevertheless, we found no independent predictor of stroke recurrence among these patients.