Nuclear Magnetic Resonance-Based Metabolomics to Predict Early and Late Adverse Outcomes in Ischemic Stroke Treated with Intravenous Thrombolysis.

Metabolic perturbations and inflammatory mediators play a fundamental role in both early and late adverse post-acute ischemic stroke outcomes. Using data from the observational MAGIC (MArker bioloGici nell'Ictus Cerebrale) study, we evaluated the effect of 130 serum metabolic features, using a nuclear magnetic spectroscopy approach, on the following outcomes: hemorrhagic transformation at 24 h after stroke, non-response to intravenous thrombolytic treatment with the recombinant tissue plasminogen activator (rt-PA), and the 3 month functional outcome. Blood circulating metabolites, lipoproteins, and inflammatory markers were assessed at the baseline and 24 h after rt-PA treatment. Adjusting for the major determinants for unfavorable outcomes (i.e., age, sex, time onset-to-treatment, etc.), we found that acetone and 3-hydroxybutyrate were associated with symptomatic hemorrhagic transformation and with non-response to rt-PA; while 24 h after rt-PA, levels of triglycerides high-density lipoprotein (HDL) and triglycerides low-density lipoprotein (LDL) were associated with 3 month mortality. Cholesterol and phospholipids levels, mainly related to smaller and denser very low-density lipoprotein (VLDL) and LDL subfractions were associated with 3 month poor functional outcomes. We also reported associations between baseline 24 h relative variation (Δ) in VLDL subfractions and ΔC-reactive protein, Δinterleukin-10 levels with hemorrhagic transformation. All observed metabolic changes reflect a general condition of energy failure, oxidative stress, and systemic inflammation that characterize the development of adverse outcomes.

Association of the careggi collateral score with radiological outcomes after thrombectomy for stroke with an occlusion of the middle cerebral artery.

We aimed to examine the association between Careggi Collateral Score (CCS) and radiological outcomes in a large multicenter cohort of patients receiving thrombectomy for stroke with occlusion of middle cerebral artery (MCA). We conducted a study on prospectively collected data from 1785 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. According to the extension of the retrograde reperfusion in the cortical anterior cerebral artery-MCA territories, CCS ranges from 0 (absence of retrograde filling) to 4 (visualization of collaterals until the alar segment of the MCA). Radiological outcomes at 24 h were the presence and severity of infarct growth defined by the absolute change in ASPECTS from baseline to 24 h; presence and severity of cerebral bleeding defined as no ICH, HI-1, HI-2, PH-1, or PH-2; presence and severity of cerebral edema (CED) defined as no CED, CED-1, CED-2, or CED-3. Using CCS = 0 as reference, ORs of CCS grades were significantly associated in the direction of better radiological outcome on infarct growth (0.517 for CCS = 1, 0.413 for CCS = 2, 0.358 for CCS = 3, 0.236 for CCS = 4), cerebral bleeding grading (0.485 for CCS = 1, 0.445 for CCS = 2, 0.400 for CCS = 3, 0.379 for CCS = 4), and CED grading (0.734 for CCS = 1, 0.301 for CCS = 2, 0.295 for CCS = 3, 0.255 for CSS = 4) shift in ordinal regression analysis after adjustment for pre-defined variables (age, NIHSS score, ASPECTS, occlusion site, onset-to-groin puncture time, procedure time, and TICI score). Using CCS = 4 as reference, ORs of CCS grades were significantly associated in the direction of worse radiological outcome on infarct growth (1.521 for CCS = 3, 1.754 for CCS = 2, 2.193 for CCS = 1, 4.244 for CCS = 0), cerebral bleeding grading (2.498 for CCS = 0), and CED grading (1.365 for CCS = 2, 2.876 for CCS = 1, 3.916 for CCS = 0) shift. The CCS could improve the prognostic estimate of radiological outcomes in patients receiving thrombectomy for stroke with MCA occlusion.

Carotid revascularization and cognitive impairment: the neglected role of cerebral small vessel disease.

Carotid atherosclerosis is a pathological process that leads to narrowing of the vessel lumen and a consequent risk of stroke. Revascularization procedures such as carotid endarterectomy (CEA) and carotid stenting aim to reduce occurrence of stroke in selected patients. Due to the proven benefit and low intraoperative risk, CEA is currently the preferred choice in candidates for carotid revascularization. However, the risk of cognitive impairment subsequent to CEA has not been fully elucidated and is unclear whether certain conditions, such as frailty, may increase this risk. There is consistent evidence that shows that frail patients have higher risk of cognitive impairment after surgical procedure. Moreover, brain pre-existing conditions may play a role in cognitive impairment after CEA. Cerebral small vessel disease (SVD) is a pathology that involves microcirculation and is detectable with computed tomography or magnetic resonance. SVD shares common vascular risk factors with carotid atherosclerosis, is a major contributor to vascular cognitive impairment and vascular dementia, and has been proposed as a marker of brain frailty. In this review, we discuss the current evidence about the link between carotid revascularization and cognitive impairment and advance the hypothesis that SVD may play a relevant role in development of cognitive impairment after carotid revascularization.

Fabry-Stroke Italian Registry (FSIR): a nationwide, prospective, observational study about incidence and characteristics of Fabry-related stroke in young-adults. Presentation of the study protocol.

BACKGROUND: TIA and stroke, both ischemic and hemorrhagic, may complicate Fabry disease at young-adult age and be the first manifestation that comes to the clinician's attention. No definite indications have yet been elaborated to guide neurologists in Fabry disease diagnostics. In current practice, it is usually sought in case of cryptogenic strokes (while Fabry-related strokes can also occur by classical pathogenic mechanisms) or through screening programs in young cerebrovascular populations. Data on recurrence and secondary prevention of Fabry's stroke are scanty. METHODS: The study had a prospective observational design involving 33 Italian neurological Stroke Units. Considering the incidence of TIA/stroke in the European population aged < 60 years and the frequency of Fabry disease in this category (as foreseen by a pilot study held at the Careggi University-Hospital, Florence), we planned to screen for Fabry disease a total of 1740 < 60-year-old individuals hospitalized for TIA, ischemic, or hemorrhagic stroke. We investigated TIA and stroke pathogenesis through internationally validated scales and we gathered information on possible early signs of Fabry disease among all cerebrovascular patients. Every patient was tested for Fabry disease through dried blood spot analysis. Patients who received Fabry disease diagnosis underwent a 12-month follow-up to monitor stroke recurrence and multi-system progression after the cerebrovascular event. DISCUSSION: The potential implications of this study are as follows: (i) to add information about the yield of systematic screening for Fabry disease in a prospective large cohort of acute cerebrovascular patients; (ii) to deepen knowledge of clinical, pathophysiological, and prognostic characteristics of Fabry-related stroke.

Influence of atrial fibrillation subtypes on anticoagulant therapy in a high-risk older population: the FAI project.

BACKGROUND AND AIM: Benefits of oral anticoagulants (OAC) in atrial fibrillation (AF) patients with moderate-to-high risk of stroke are independent of AF pattern. We evaluated whether AF clinical subtype influenced OAC use in a representative sample of the Italian older population. METHODS: A cross-sectional examination of all subjects aged 65 + years from three general practices in northern, central, and southern Italy started in 2016. A double-screening procedure was followed by clinical and ECG confirmation. Patients were categorized as having paroxysmal, persistent, or permanent AF. OAC use was evaluated in confirmed AF patients. RESULTS: The sample included 6016 subjects. Excluding 235 non-eligible, participation was 78.3%, which left 4528 participants (mean age 74.5 ± 6.8 years, 47.2% men). Overall, 319 AF cases were identified: 43.0% had paroxysmal, 21.3% persistent, and 35.7% permanent AF. Frequency of OAC therapy was 91.2% in permanent, 85.3% in persistent, and only 43.0% in paroxysmal AF (P < 0.001). In multivariate analysis, controlled for baseline variables and risk scales, persistent and permanent AF were associated with a significant increase in the likelihood of receiving OAC compared with paroxysmal AF (P < 0.001). This was confirmed for permanent AF also in multivariate analyses considering separately vitamin K antagonists or direct-acting oral anticoagulants (OR, 4.37, 95% CI, 2.43-7.85; and 1.92, 95% CI, 1.07-3.42, respectively) and for persistent AF and direct-acting oral anticoagulants (OR, 4.33, 95% CI, 2.30-8.15). CONCLUSIONS: In a population-based survey, AF pattern was an independent predictor of OAC treatment. Paroxysmal AF is still perceived as carrying a lower risk of vascular events.

Analysis of Metabolite and Lipid Association Networks Reveals Molecular Mechanisms Associated with 3-Month Mortality and Poor Functional Outcomes in Patients with Acute Ischemic Stroke after Thrombolytic Treatment with Recombinant Tissue Plasminogen Activator.

Here, we present an integrated multivariate, univariate, network reconstruction and differential analysis of metabolite-metabolite and metabolite-lipid association networks built from an array of 18 serum metabolites and 110 lipids identified and quantified through nuclear magnetic resonance spectroscopy in a cohort of 248 patients, of which 22 died and 82 developed a poor functional outcome within 3 months from acute ischemic stroke (AIS) treated with intravenous recombinant tissue plasminogen activator. We explored differences in metabolite and lipid connectivity of patients who did not develop a poor outcome and who survived the ischemic stroke from the related opposite conditions. We report statistically significant differences in the connectivity patterns of both low- and high-molecular-weight metabolites, implying underlying variations in the metabolic pathway involving leucine, glycine, glutamine, tyrosine, phenylalanine, citric, lactic, and acetic acids, ketone bodies, and different lipids, thus characterizing patients' outcomes. Our results evidence the promising and powerful role of the metabolite-metabolite and metabolite-lipid association networks in investigating molecular mechanisms underlying AIS patient's outcome.

Bridging versus direct endovascular therapy in basilar artery occlusion.

BACKGROUND: We evaluated safety and efficacy of intravenous recombinant tissue Plasminogen Activator plus endovascular (bridging) therapy compared with direct endovascular therapy in patients with ischaemic stroke due to basilar artery occlusion (BAO). METHODS: From a national prospective registry of endovascular therapy in acute ischaemic stroke, we selected patients with BAO. We compared bridging and direct endovascular therapy evaluating vessel recanalisation, haemorrhagic transformation at 24-36 hours; procedural complications; and functional outcome at 3 months according to the modified Rankin Scale. We ran logistic and ordinal regression models adjusting for age, sex, National Institutes of Health Stroke Scale (NIHSS), onset-to-groin-puncture time. RESULTS: We included 464 patients, mean(±SD) age 67.7 (±13.3) years, 279 (63%) males, median (IQR) NIHSS=18 (10-30); 166 (35%) received bridging and 298 (65%) direct endovascular therapy. Recanalisation rates and symptomatic intracerebral haemorrhage were similar in both groups (83% and 3%, respectively), whereas distal embolisation was more frequent in patients treated with direct endovascular therapy (9% vs 3%; p=0.009). In the whole population, there was no difference between bridging and direct endovascular therapy regarding functional outcome at 3 months (OR=0.79; 95% CI=0.55 to 1.13). However, in patients with onset-to-groin-puncture time ≤6 hours, bridging therapy was associated with lower mortality (OR=0.53; 95% CI=0.30 to 0.97) and a shift towards better functional outcome in ordinal analysis (OR=0.65; 95% CI=0.42 to 0.98). CONCLUSIONS: In ischaemic stroke due to BAO, when endovascular therapy is initiated within 6 hours from symptoms onset, bridging therapy resulted in lower mortality and better functional outcome compared with direct endovascular therapy.

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.

Global Burden of Small Vessel Disease-Related Brain Changes on MRI Predicts Cognitive and Functional Decline.

Background and Purpose- Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple types of small vessel disease-related brain changes and examined their individual and combined predictive value on cognitive and functional abilities. Methods- Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network-based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years. Results- The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi (P<0.001 for global cognitive function, processing speed, executive functions, and memory and P<0.001 for poor functional outcome). Volumes of lacunes, enlarged perivascular spaces, and cortical infarcts were significantly associated with part of the outcome measures, but their contribution was weaker. In a multivariable linear mixed model, volumes of white matter hyperintensities, lacunes, gray matter, and hippocampi remained as independent predictors of cognitive impairment. A combined measure of these markers based on Z scores strongly predicted cognitive and functional outcomes (P<0.001) even above the contribution of the individual brain changes. Conclusions- Global burden of small vessel disease-related brain changes as quantified by an image segmentation tool is a powerful predictor of long-term cognitive decline and functional disability. A combined measure of white matter hyperintensities, lacunar, gray matter, and hippocampal volumes could be used as an imaging marker associated with vascular cognitive impairment.

General Anesthesia Versus Conscious Sedation and Local Anesthesia During Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: As numerous questions remain about the best anesthetic strategy during thrombectomy, we assessed functional and radiological outcomes in stroke patients treated with thrombectomy in presence of general anesthesia (GA) versus conscious sedation (CS) and local anesthesia (LA). METHODS: We conducted a cohort study on prospectively collected data from 4429 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. RESULTS: GA was used in 2013 patients, CS in 1285 patients, and LA in 1131 patients. The rates of 3-month modified Rankin Scale score of 0-1 were 32.7%, 33.7%, and 38.1% in the GA, CS, and LA groups: GA versus CS: odds ratios after adjustment for unbalanced variables (adjusted odds ratio [aOR]), 0.811 (95% CI, 0.602-1.091); and GA versus LA: aOR, 0.714 (95% CI, 0.515-0.990). The rates of modified Rankin Scale score of 0-2 were 42.5%, 46.6%, and 52.4% in the GA, CS, and LA groups: GA versus CS: aOR, 0.902 (95% CI, 0.689-1.180); and GA versus LA: aOR, 0.769 (95% CI, 0.566-0.998). The rates of 3-month death were 21.5%, 19.7%, and 14.8% in the GA, CS, and LA groups: GA versus CS: aOR, 0.872 (95% CI, 0.644-1.181); and GA versus LA: aOR, 1.235 (95% CI, 0.844-1.807). The rates of parenchymal hematoma were 9%, 12.6%, and 11.3% in the GA, CS, and LA groups: GA versus CS: aOR, 0.380 (95% CI, 0.262-0.551); and GA versus LA: aOR, 0.532 (95% CI, 0.337-0.838). After model of adjustment for predefined variables (age, sex, thrombolysis, National Institutes of Health Stroke Scale, onset-to-groin time, anterior large vessel occlusion, procedure time, prestroke modified Rankin Scale score of <1, antiplatelet, and anticoagulant), differences were found also between GA versus CS as regards modified Rankin Scale score of 0-2 (aOR, 0.659 [95% CI, 0.538-0.807]) and GA versus LA as regards death (aOR, 1.413 [95% CI, 1.095-1.823]). CONCLUSIONS: GA during thrombectomy was associated with worse 3-month functional outcomes, especially when compared with LA. The inclusion of an LA arm in future randomized clinical trials of anesthesia strategy is recommended.

Endovascular Thrombectomy for Acute Ischemic Stroke Beyond 6 Hours From Onset: A Real-World Experience.

BACKGROUND AND PURPOSE: To evaluate outcome and safety of endovascular treatment beyond 6 hours of onset of ischemic stroke due to large vessel occlusion in the anterior circulation, in routine clinical practice. METHODS: From the Italian Registry of Endovascular Thrombectomy, we extracted clinical and outcome data of patients treated for stroke of known onset beyond 6 hours. Additional inclusion criteria were prestroke modified Rankin Scale score ≤2 and ASPECTS score ≥6. Patients were selected on individual basis by a combination of CT perfusion mismatch (difference between total hypoperfusion and infarct core sizes) and CT collateral score. The primary outcome measure was the score on modified Rankin Scale at 90 days. Safety outcomes were 90-day mortality and the occurrence of symptomatic intracranial hemorrhage. Data were compared with those from patients treated within 6 hours. RESULTS: Out of 3057 patients, 327 were treated beyond 6 hours. Their mean age was 66.8±14.9 years, the median baseline National Institutes of Health Stroke Scale 16, and the median onset to groin puncture time 430 minutes. The most frequent site of occlusion was middle cerebral artery (45.1%). Functional independence (90-day modified Rankin Scale score, 0-2) was achieved by 41.3% of cases. Symptomatic intracranial hemorrhage occurred in 6.7% of patients, and 3-month case fatality rate was 17.1%. The probability of surviving with modified Rankin Scale score, 0-2 (odds ratio, 0.58 [95% CI, 0.43-0.77]) was significantly lower in patients treated beyond 6 hours as compared with patients treated earlier No differences were found regarding recanalization rates and safety outcomes between patients treated within and beyond 6 hours. There were no differences in outcome between people treated 6-12 hours from onset (278 patients) and those treated 12 to 24 hours from onset (49 patients). CONCLUSIONS: This real-world study suggests that in patients with large vessel occlusion selected on the basis of CT perfusion and collateral circulation assessment, endovascular treatment beyond 6 hours is feasible and safe with no increase in symptomatic intracranial hemorrhage.

Correction to: "When should primary angiitis of the central nervous system (PACNS) be suspected?": literature review and proposal of a preliminary screening algorithm.

The above article was published online with inverted given and family names. The correct presentation has been corrected above. The original article has been corrected.

"When should primary angiitis of the central nervous system (PACNS) be suspected?": literature review and proposal of a preliminary screening algorithm.

BACKGROUND: Primary angiitis of the CNS (PACNS) is a process causing variously combined neurological disturbances. Its rarity and kaleidoscopic presentation make it difficult to diagnose and even to suspect. OBJECTIVE: (1) To provide an up-to-date review on PACNS and (2) to create a preliminary screening algorithm based on clinical and radiological first-level data, useful to suspect PACNS and guide further investigations. METHODS: Review of PUBMED case series on PACNS, published from 2002 to 2017, collection of frequencies of clinical and neuroimaging features and calculation of median values. Classification of features as "major" or "minor" if frequency was higher or lower than median value. Combination of features in sets of criteria represented by all possible combinations of major and minor clinical and neuroradiological features. Application of criteria to published PACNS case reports and selection of the ones best identifying patients with definite PACNS. RESULTS: We reviewed 24 case series. "Major" clinical features were headache, stroke, cognitive impairment, focal neurological deficits; "minor" were seizures, altered consciousness, psychiatric disorders. "Major" neuroradiological features were multiple parenchymal lesions, parenchymal/meningeal contrast enhancement, magnetic resonance angiography vessel abnormalities, vessel wall enhancement; "minor" were parenchymal/subarachnoid hemorrhage, single parenchymal lesion. The selected sets of criteria able to identify all PACNS patients were (1) one clinical (major/minor) + one major neuroradiological feature; and (2) Two clinical (≥ 1 major) + one minor neuroradiological feature. CONCLUSION: Our review provides a detailed clinical/neuroradiological picture of PACNS. The proposed algorithm should be regarded as a preliminary screening tool to move the first steps towards PACNS diagnosis that needs validation.

Mechanical thrombectomy in patients with proximal occlusions and low NIHSS: Results from a large prospective registry.

BACKGROUND: Mechanical thrombectomy is now standard of care for treatment of acute ischemic stroke secondary to large vessel occlusion in the setting of high NIHSS. We analysed a large nationwide registry focusing on patients with large vessel occlusion and low NIHSS on admission to evaluate the efficacy and safety of thrombectomy in this patient population METHODS: 2826 patients treated with mechanical thrombectomy were included in a multicentre registry from January 1, 2011 to December 31, 2015. We included patients with large vessel occlusion and NIHSS ≤ 6 on admission. Baseline characteristics, imaging, clinical outcome, procedure adverse events and positive and negative outcome predictors were analysed. RESULTS: 134 patients were included. 90/134 had an anterior circulation and 44 a posterior circulation stroke. One patient died before treatment. Successful revascularization (mTICI 2b-3) was achieved in 73.7% (98/133) of the patients. Intraprocedural adverse event was observed in 3% (4/133) of cases. Symptomatic intracranial haemorrhage rate was 5.3% (7/133). At three months, 70.9% (95/134) of the patients had mRS score 0-2, 15.7% (21/134) mRS 3-5 and 13.4% (18/134) mRS 6. Age and successful recanalization were significant predictors of a good clinical outcome on both univariate (p= 0.005 and p=0.007) and multivariable (p=0.0018 and p=0.009 [nat log]) analysis. Absence of vessel recanalization and symptomatic intracranial hemorrhage were independent predictors of poor outcome (p=0.021) . CONCLUSIONS: Our study suggests that patients with large vessel occlusion and low NIHSS score on admission can benefit from mechanical thrombectomy. Randomized trials are warranted.

Prevalence of atrial fibrillation in the Italian elderly population and projections from 2020 to 2060 for Italy and the European Union: the FAI Project.

AIMS: To estimate prevalence of atrial fibrillation (AF) in a representative sample of the Italian elderly population, projecting figures for Italy and the European Union. METHODS AND RESULTS: A cross-sectional examination of all subjects aged 65+ years from three general practices in Northern, Central, and Southern Italy started in 2016. Participants were administered a systematic and an opportunistic screening, followed by clinical and electrocardiogram confirmation. The study sample included 6016 subjects. Excluding 235 non-eligible, among the remaining 5781 participation was 78.3%, which left 4528 participants (mean age 74.5 ± 6.8 years, 47.2% men). Prevalence of AF was 7.3% [95% confidence intervals (CI) 6.6-8.1], higher in men and with advancing age (6.6% from systematic plus 0.7% from opportunistic screening). Using prevalence figures, Italian elderly having AF in 2016 were estimated at ∼1 081 000 (95% CI 786 000-1 482 000). Considering stable prevalence, this number will increase by 75% to ∼1 892 000 in 2060 (95% CI 1 378 000-2 579 000). European Union elderly having AF in 2016 were estimated at ∼7 617 000 (95% CI 5 530 000-10 460 000), increasing by 89% to ∼14 401 000 in 2060 (95% CI 10 489 000-19 647 000). In 2016, subjects aged 80+ years represented 53.5% of cases in Italy and 51.2% in the European Union; in 2060, 69.6% and 65.2%, respectively. CONCLUSIONS: Our findings indicate a high burden of AF in coming decades, especially among the oldest-old, who carry the higher AF-related risk of stroke and medical complications.

Small vessel disease and clinical outcomes after endovascular treatment in acute ischemic stroke.

BACKGROUND: Pre-existing small vessel disease (SVD) has been associated with poor functional outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis; however, there are scarce data in patients treated with endovascular therapy. We aimed to investigate the associations between SVD and clinical outcomes in patients treated with endovascular therapy. METHODS: We retrospectivel y evaluated patients with acute ischemic stroke in the anterior circulation receiving endovascular treatment. We assessed SVD markers with visual scales using non-contrast computed tomography. Early outcomes included intracerebral hemorrhage and 7-day/discharge stroke severity, and late outcomes included modified Rankin scale (mRS) 90 days after stroke. We used logistic and ordinal regression models adjusted for age, sex, stroke severity, and time-to-groin puncture time. RESULTS: A total of 175 patients were included in the study, mean (±SD) age 72.3 (± 12.4) years, 90 (51%) males. Among SVD features, only brain atrophy was associated with 7-day stroke severity (OR = 2.28; 95% CI = 1.11-4.68) and with worse mRS at 90 days (OR = 2.72; 95% CI = 1.25-5.91). Global SVD burden was associated with worse mRS at 90 days (OR = 1.63; 95% CI = 1.01-2.62) but not with 7-day stroke severity (OR = 1.71; 95% CI = 0.97-3.01). CONCLUSIONS: Pre-existing SVD burden, mainly driven by brain atrophy, negatively affects early and late clinical outcomes in anterior circulation ischemic stroke treated with endovascular therapy. Our results may help prognostic stratification of stroke patients treated with endovascular therapy.

Biopsychosocial frailty and the risk of incident dementia: The Italian longitudinal study on aging.

INTRODUCTION: Frailty is a critical intermediate status of the aging process including physical, cognitive, and psychosocial domains/phenotypes. We operationalized a new biopsychosocial frailty (BF) construct, estimating its impact on the risk of incident dementia and its subtypes. METHODS: In 2171 older individuals from the population-based Italian Longitudinal Study on Aging (ILSA), we identified by latent class procedures the BF construct as the physical frail status plus at least one of the two items of the 30-item Geriatric Depression Scale impaired (items 3/10). RESULTS: Over a 3.5-year follow-up, participants with BF showed an increased risk of overall dementia (hazard ratio [HR]: 2.16, 95% confidence interval [CI]:1.07-4.37), particularly vascular dementia (VaD) (HR: 3.21, 95% CI: 1.05-9.75). Similarly, over a 7-year follow-up, an increased risk of overall dementia (HR: 1.84, 95% CI: 1.06-3.20), particularly VaD (HR: 2.53, 95% CI: 1.08-5.91), was also observed. DISCUSSION: In a large cohort of Italian older individuals without cognitive impairment at baseline, a BF model was a short- and long-term predictor of overall dementia, particularly VaD.

Additive Role of a Potentially Reversible Cognitive Frailty Model and Inflammatory State on the Risk of Disability: The Italian Longitudinal Study on Aging.

OBJECTIVE: Cognitive frailty is a condition recently defined by operationalized criteria describing the simultaneous presence of physical frailty and mild cognitive impairment (MCI). Two subtypes for this clinical construct have been proposed: "potentially reversible" cognitive frailty (physical frailty plus MCI) and "reversible" cognitive frailty (physical frailty plus pre-MCI subjective cognitive decline). Here the prevalence of a potentially reversible cognitive frailty model was estimated. It was also evaluated if introducing a diagnosis of MCI in older subjects with physical frailty could have an additive role on the risk of dementia, disability, and all-cause mortality in comparison with frailty state or MCI condition alone, with analyses separately performed for inflammatory state. METHODS: In 2,373 individuals from the population-based Italian Longitudinal Study on Aging with a 3.5-year-follow-up, we operationally categorized older individuals without dementia into four groups: non-frail/non-MCI, non-frail/MCI, frail/non-MCI, and frail/MCI. RESULTS: The prevalence of potentially reversible cognitive frailty was 1%, increasing with age and more represented in women than in men, and all groups were associated with significant increased incident rate ratios of dementia, disability, and mortality. A significant difference in rates of disability has been found between the MCI and non-MCI groups (contrasts of adjusted predictions: 0.461; 95% confidence interval: 0.187-0.735) in frail individuals with high inflammatory states (fibrinogen >339 mg/dL). CONCLUSION: In older individuals without dementia and with elevated inflammation, a potentially reversible cognitive frailty model could have a significant additional predictive effect on the risk of disability than the single conditions of frailty or MCI.

Blood markers of inflammation and endothelial dysfunction in cardioembolic stroke: systematic review and meta-analysis.

CONTEXT: Various processes including inflammation and endothelial dysfunction have been implicated in the pathogenesis of cardioembolic (CE) strokes. OBJECTIVE: To review the evidence and investigate the association between immune-inflammatory biomarkers and CE strokes versus other stroke subtypes. METHODS: We systematically reviewed the literature (sources: MEDLINE, web-based register http://stroke-biomarkers.com , reference lists) with quality assessment and meta-analysis of selected articles. RESULTS: The most consistent association was found between C-reactive protein (CRP) and CE strokes when compared to other stroke subtypes (standardized mean difference 0.223 (0.116, 0.343); p < 0.001) Conclusions: Our findings confirm a possible association between selected inflammatory biomarkers and CE stroke.

Use of rivaroxaban in patients with stroke.

Rivaroxaban, an inhibitor of Factor Xa, is a direct oral anti-coagulant that has been found to be non-inferior to warfarin in preventing cerebral ischemia in patients with non-valvular atrial fibrillation and in the subgroup of patients with a history of the previous stroke or transient ischemic attack. Vascular neurologists in daily clinical practice may encounter patients taking rivaroxaban or patients who may benefit from its use. In this paper, we review the current clinical indications, contraindications, and clinical management guidelines for rivaroxaban while providing a special focus on neurological aspects and expert opinions on rivaroxaban therapy management in various situations that a neurologist may encounter when treating patients with an ischemic stroke (including those requiring intravenous or intra-arterial reperfusion therapy) and patients with an intracerebral hemorrhage. Since data from clinical trials and real-life data are missing in some clinical situations, strong recommendations are not always available. Nevertheless, practical guidelines should be adopted to maximize benefits from this oral anti-coagulant.