Blood-brain barrier leakage and hemorrhagic transformation: The Reperfusion Injury in Ischemic StroKe (RISK) study.

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke treated with reperfusion therapy we aimed to evaluate whether pretreatment blood-brain barrier (BBB) leakage is associated with subsequent hemorrhagic transformation (HT). METHODS: We prospectively screened patients with acute ischemic stroke treated with intravenous thrombolysis and/or endovascular treatment. Before treatment, each patient received computed tomography (CT), CT angiography, and CT perfusion. We assessed pretreatment BBB leakage within the ischemic area using the volume transfer constant (Ktrans ) value. Our primary outcome was relevant HT, defined as hemorrhagic infarction type 2 or parenchymal hemorrhage type 1 or 2. We evaluated independent associations between BBB leakage and HT using logistic regression, adjusting for age, sex, baseline stroke severity, Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6, treatment type, and onset-to-treatment time. RESULTS: We enrolled 171 patients with available assessment of BBB leakage. The patients' mean (±SD) age was 75.5 (±11.8) years, 86 (50%) were men, and the median (interquartile range) National Institutes of Health Stroke Scale score was 18 (12-23). A total of 32 patients (18%) received intravenous thrombolysis, 102 (60%) underwent direct endovascular treatment, and 37 (22%) underwent both. Patients with relevant HT (N = 31;18%) had greater mean BBB leakage (Ktrans 0.77 vs. 0.60; p = 0.027). After adjustment in the logistic regression model, we found that BBB leakage was associated both with a more than twofold risk of relevant HT (odds ratio [OR] 2.50; 95% confidence interval [CI] 1.03-6.03 per Ktrans point increase; OR 2.34; 95% CI 1.06-5.17 for Ktrans values > 0.63 [mean BBB leakage value]) and with symptomatic intracerebral hemorrhage (OR 4.30; 95% CI 1.13-13.77 per Ktrans point increase). CONCLUSION: Pretreatment BBB leakage before reperfusion therapy was associated with HT, and may help to identify patients at risk of HT.

Reperfusion Injury after ischemic Stroke Study (RISKS): single-centre (Florence, Italy), prospective observational protocol study.

INTRODUCTION: Treatments aiming at reperfusion of the acutely ischaemic brain tissue may result futile or even detrimental because of the so-called reperfusion injury. The processes contributing to reperfusion injury involve a number of factors, ranging from blood-brain barrier (BBB) disruption to circulating biomarkers. Our aim is to evaluate the relative effect of imaging and circulating biomarkers in relation to reperfusion injury. METHODS AND ANALYSIS: Observational hospital-based study that will include 140 patients who had ischaemic stroke, treated with systemic thrombolysis, endovascular treatment or both. BBB disruption will be assessed with CT perfusion (CTP) before treatment, and levels of a large panel of biomarkers will be measured before intervention and after 24 hours. Relevant outcomes will include: (1) reperfusion injury, defined as radiologically relevant haemorrhagic transformation at 24 hours and (2) clinical status 3 months after the index stroke. We will investigate the separate and combined effect of pretreatment BBB disruption and circulating biomarkers on reperfusion injury and clinical status at 3 months. Study protocol is registered at http://www.clinicaltrials.gov (ClinicalTrials.gov ID: NCT03041753). ETHICS AND DISSEMINATION: The study protocol has been approved by ethics committee of the Azienda Ospedaliero Universitaria Careggi (Università degli Studi di Firenze). Informed consent is obtained by each patient at time of enrolment or deferred when the participant lacks the capacity to provide consent during the acute phase. Researchers interested in testing hypotheses with the data are encouraged to contact the corresponding author. Results from the study will be disseminated at national and international conferences and in medical thesis. TRIAL REGISTRATION NUMBER: NCT03041753.

Impact of acute-phase complications and interventions on 6-month survival after stroke. A prospective observational study.

The outcome of stroke patients is complex and multidimensional. We evaluated the impact of acute-phase variables, including clinical state, complications, resource use and interventions, on 6-month survival after first-ever stroke, taking into account baseline conditions exerting a possible effect on outcome. As part of a National Research Program, we performed a prospective observational study of acute stroke patients in four Italian Regions. Consecutive patients admitted for a period of 3 months to the emergency rooms of participating hospitals were included. A total of 1030 patients were enrolled (median age 76.0 years, 52.1% males). At 6 months, 816 (79.2%) were alive, and 164 (15.9%) deceased. Survival status at the 6-month follow-up was missing for 50 (4.9%). Neurological state in the acute phase was significantly worse in patients deceased at 6 months, who showed also higher frequency of acute-phase complications. Cox regression analysis adjusted for demographics, pre-stroke function, baseline diseases and risk factors, indicated as significant predictors of 6-month death altered consciousness (HR, 1.70; 95% CI, 1.14-2.53), total anterior circulation infarct (HR, 2.13; 95% CI, 1.44-3.15), hyperthermia (HR, 1.70; 95% CI, 1.18-2.45), pneumonia (HR, 1.76; 95% CI, 1.18-2.61), heart failure (HR, 2.87; 95% CI, 1.34-6.13) and nasogastric feeding (HR, 2.35; 95% CI, 1.53-3.60), while antiplatelet therapy during acute phase (HR, 0.56; 95% CI, 0.39-0.79), and early mobilisation (HR, 0.55; 95% CI, 0.36-0.84) significantly increased 6-month survival. In a prospective observational study, stroke severity and some acute-phase complications, potentially modifiable, significantly increased the risk of 6-month death, independently of baseline variables. Early mobilisation positively affected survival, highlighting the role of early rehabilitation after stroke.

Resolution of Anton-Babinski syndrome after systemic thrombolysis and mechanical thrombectomy with a stentriever.

Anton-Babinski syndrome is a rare neuropsychiatric syndrome characterized by bilateral cortical blindness and anosognosia with visual confabulation. We present the case of a patient presenting with occlusion of both posterior cerebral arteries (PCA), with Anton-Babinski syndrome, completely solved after combined systemic thrombolysis and mechanical thrombectomy with a stent-retriever.

Daily Function as Predictor of Dementia in Cognitive Impairment, No Dementia (CIND) and Mild Cognitive Impairment (MCI): An 8-Year Follow-Up in the ILSA Study.

BACKGROUND: Preclinical cognitive changes may predict an increased risk of dementia, allowing selection of subgroups as possible targets for preventive or therapeutic interventions. OBJECTIVE: To evaluate the predictive effect of daily functioning and motor performance (MP) on the progression to dementia in normal cognition, cognitive impairment, no dementia (CIND), and mild cognitive impairment (MCI). METHODS: The Italian Longitudinal Study on Aging is a large population-based survey on age-related diseases of the cardiovascular and nervous systems. After the baseline assessment, to detect prevalent cases of cognitive impairment and dementia, participants were re-examined at 4-year and 8-year follow-ups. Functional independence was evaluated using the Index of Activities of Daily Living (ADL) and the Instrumental Activities of Daily Living (IADL) Scale. A six-test battery was used to assess MP. RESULTS: Overall, 2,386 individuals were included, for a total of 16,545 person-years. Eight-year incidence of dementia (per 1,000 person-years) was 12.69 in total sample, 9.86 in subjects with normal cognition at baseline, 22.99 in CIND, and 21.43 in MCI. Progression to dementia was significantly higher with increasing baseline ADL and IADL impairment, and with a worse MP. In Cox regression analyses controlled for demographics and major age-related conditions, increased IADL impairment was the stronger predictor of progression to dementia (p < 0.001), with HR ranging from 2.16 (95% CI, 0.82-5.70) to 9.57 (95% CI, 3.40-26.91) in subjects with MCI at baseline. CONCLUSIONS: Inclusion of IADL in the MCI construct significantly improves the prediction of dementia. Individuation of different transition rates is required to plan cost-effective interventions.

Quality indicators in acute stroke care: a prospective observational survey in 13 Italian regions.

BACKGROUND AND AIMS: Quality monitoring has great relevance in stroke care. The Project "How to guarantee adherence to effective interventions in stroke care" aimed to estimate adherence to acute-phase guidelines in stroke care in Italy. METHODS: A prospective observational study was performed in 27 hospitals of 13 Italian Regions. Adherence to 15 process indicators was evaluated, comparing also stroke units (SU) with conventional wards. An overall score of care, defined as the sum of achieved indicators, was calculated. A multilevel hierarchical model described performance at patient, hospital and regional level. RESULTS: Overall, 484 consecutive stroke patients (mean age, 73.4 years; 52.7 % males) were included. Total score ranged from 2 to 15 (mean 8.5 ± 2.4). SU patients were more often evaluated with the National Institutes of Health Stroke Scale (NIHSS) within 24 h, had more frequently an assessment of pre- and post-stroke disability, and a CT scan the same or the day after admission. Regional-hospital- and patient-level variability explained, respectively, 25, 34, and 41 % of total score variance. In multivariate models, patients >80 years vs. younger showed a change in total score of -0.45 (95 % CI -0.79 to -0.12), and those with NIHSS ≥14 vs. ≤5 of -0.92 (95 % CI -1.53 to -0.30). A negative change means a worse adjusted average adherence to process indicators. SU admission increased total score of 1.55 (95 % CI 0.52-2.58). CONCLUSIONS: Our data confirm the need of quality monitoring in stroke care. Although SU patients showed a better adherence to quality indicators, overall compliance was unsatisfactory.

Progressive lacunar stroke: review of mechanisms, prognostic features, and putative treatments.

Lacunar stroke is generally considered to have a fair outcome. However 20-30% of patients with lacunar stroke worsen neurologically in hours or days after onset, reaching eventually an unexpectedly severe disability status. In the field of acute stroke, progressive lacunar stroke remains an important unresolved practice problem, because as yet no treatment does exist proven to prevent or halt progression. Pathophysiology of progression is yet incompletely understood. Hemodynamic factors, extension of thrombosis, excitotoxicity, and inflammation, have been proposed as possible mechanisms of progression. A few clinical studies also aimed at establishing presentation features that may help identifying patients at risk of deterioration. In this paper, we review hypothesized mechanisms of lacunar stroke progression and possible markers of early deterioration. Moreover, based on putative mechanisms and suggestions from reported evidence, we propose a few treatments that seem worthy to be tested by randomized clinical trials.

Selective risk factors profiles and outcomes among patients with stroke and history of prior myocardial infarction. The European Community Stroke Project.

BACKGROUND AND OBJECTIVE: Previous myocardial infarction (MI) has been linked with poorer stroke outcome. Whether this depends on a greater stroke severity is still uncertain. The aim of the study was to assess the effect of previous MI on characteristics and outcome of stroke in a large hospital cohort of patients. METHODS: In a European Union Concerted Action, patients hospitalized for first-in-a-lifetime stroke were assessed for demographics, risk factors, clinical presentation, and 3-month survival and handicap. RESULTS: Out of 4190 study patients, 460 (11%) reported a history of MI. Compared with patients without previous MI, those with MI were significantly older, more often males, smokers, alcohol consumers, and with a more severe pre-stroke level of handicap. They had more frequently atrial fibrillation and a history of transient ischemic attack. The acute neurological state and the 28-day mortality did not differ between the two groups. At 3 months, death or severe handicap were more frequent in the MI group (28.3% vs. 21.7%, P=0.001; 74.8% vs. 65.8%, P=0.008). Controlling by logistic regression analysis for age, sex, vascular risk factors, comorbidities, prior to stroke therapy, pre-stroke level of handicap, and clinical acute phase variables, prior MI remained an independent predictor of 3-month death (OR 1.30; 95% CI, 1.02-1.66) and 3-month handicap (OR 1.46; 95% CI, 1.01-2.11). CONCLUSIONS: Previous MI has no impact on clinical severity of acute stroke, but significantly affects 3-month outcome in terms of handicap and mortality.

Risk factors and outcome of subtypes of ischemic stroke. Data from a multicenter multinational hospital-based registry. The European Community Stroke Project.

BACKGROUND: Information on determinants and prognosis of ischemic stroke subtypes is scarce. We aimed at evaluating risk factors, pathogenesis, treatment and outcome of different ischemic stroke subtypes. METHODS: In a European Concerted Action involving seven countries, ischemic stroke subtypes defined according to the Oxfordshire Community Stroke Project (OCSP) were evaluated for demographics, baseline risk factors, resource use, 3-month survival, disability (Barthel Index) and handicap (Rankin Scale). RESULTS: During the 12-month study period, cerebral infarction was diagnosed in 2740 patients with first-in-a-lifetime stroke (mean age 70.5+/-12.4 years, 53.4% males). OCSP classification was achieved in 2472 (90.2%). Of these, 26.7% were total anterior circulation infarctions (TACI), 29.9% partial anterior circulation infarctions (PACI), 16.7% posterior circulation infarctions (POCI) and 26.7% lacunar infarctions (LACI). In multivariate analysis, atrial fibrillation was predictive of TACI (odds ratio [OR], 1.61; 95% CI, 1.28-2.03), hypertension (OR, 1.38; 95% CI, 1.16-1.65) and myocardial infarction (OR, 1.42; 95% CI, 1.08-1.86) predictive of PACI, hypertension (OR, 1.25; 95% CI, 1.04-1.50) predictive of LACI. A negative association was observed between TACI and hypertension (OR, 0.51; 95% CI, 0.42-0.61). Discharge home was 50% less probable in TACI and PACI than in LACI patients. As compared to LACI, TACI significantly increased the risk of 3-month death (OR, 5.73; 95% CI, 3.91-8.41), disability (OR, 3.27; 95% CI, 2.30-4.66) and handicap (OR, 2.71; 95% CI, 1.91-3.85). CONCLUSIONS: Ischemic stroke subtypes have different risk factors profile, with consequences on pathogenesis and prognosis. Information on determinants of the clinical syndromes may impact on prevention and acute-phase interventions.

Sex differences in the clinical presentation, resource use, and 3-month outcome of acute stroke in Europe: data from a multicenter multinational hospital-based registry.

BACKGROUND AND PURPOSE: The information on the existence of sex differences in management of stroke patients is scarce. We evaluated whether sex differences may influence clinical presentation, resource use, and outcome of stroke in a European multicenter study. METHODS: In a European Concerted Action involving 7 countries, 4499 patients hospitalized for first-in-a-lifetime stroke were evaluated for demographics, risk factors, clinical presentation, resource use, and 3-month survival, disability (Barthel Index), and handicap (Rankin Scale). RESULTS: Overall, 2239 patients were males and 2260 females. Compared with males, female patients were significantly older (mean age 74.5+/-12.5 versus 69.2+/-12.1 years), more frequently institutionalized before stroke, and with a worse prestroke Rankin score (all values P<0.001). History of hypertension (P=0.007) and atrial fibrillation (P<0.001) were significantly more frequent in female stroke patients, as were coma (P<0.001), paralysis (P<0.001), aphasia (P=0.001), swallowing problems (P=0.005), and urinary incontinence (P<0.001) in the acute phase. Brain imaging, Doppler examination, echocardiogram, and angiography were significantly less frequently performed in female than male patients (all values P<0.001). The frequency of carotid surgery was also significantly lower in female patients (P<0.001). At the 3-month follow-up, after controlling for all baseline and clinical variables, female sex was a significant predictor of disability (odds ratio [OR], 1.41; 95% CI 1.10 to 1.81) and handicap (OR, 1.46; 95% CI 1.14 to 1.86). No significant gender effect was observed on 3-month survival. CONCLUSIONS: Sex-specific differences existed in a large European study of hospital admissions for acute stroke. Both medical and sociodemographic factors may significantly influence stroke outcome. Knowledge of these determinants may positively impact quality of care.