Background and Purpose: Tenecteplase (TNK) within 4.5 h from symptom onset is not inferior to alteplase in treating ischemic stroke. In recent years, some randomized controlled trials (RCTs) have investigated the efficacy of extending the therapeutic window up to 24 h. This updated meta-analysis aims to synthesize the results of these RCTs comparing TNK to the best medical treatment (BMT) with or without endovascular thrombectomy. Methods: In accordance with PRISMA guidelines, all RCTs comparing TNK with BMT in adult patients between 4.5 and 24 h were systematically searched. The primary endpoint was good functional outcome at 90 days (mRS 0–2). Secondary endpoints included excellent outcome (mRS 0–1), symptomatic intracerebral hemorrhage (sICH), 90-day mortality, complete reperfusion at 24 h. Odd and Hazard ratios (ORs; HRs) were pooled using meta-analytic methods. Results: A total of seven RCTs involving 1754 patients were included. The rates of the primary endpoint were higher in TNK-treated patients (HR: 1.15; 95% CI: 1.03–1.27), as were rates of excellent functional outcome (HR: 1.29; 95% CI: 1.08–1.55). In the subgroup receiving intravenous therapy (IVT) alone, the primary endpoint was significantly more frequent in the TNK group than in the BMT group (OR: 1.47; 95% CI: 1.17–1.84; p for heterogeneity < 0.0001). TNK treatment was also associated with higher reperfusion rates compared with BMT, reflecting a greater proportion of saved ischemic penumbra as assessed via perfusion imaging. Although symptomatic intracranial hemorrhage (sICH) occurred more frequently in TNK-treated patients, the difference did not reach statistical significance, and mortality rates were comparable between treatment groups. Conclusions: Tenecteplase administered between 4.5 and 24 h is associated with improved rates of both good and excellent functional outcomes compared with BMT, especially in patients treated with IVT alone. Additionally, TNK is linked to higher rates of reperfusion.

Background Whether statin use after spontaneous intracerebral haemorrhage (ICH) increases the risk of recurrent ICH is uncertain. Methods In the setting of the Multicentric Study on Cerebral Haemorrhage in Italy we followed up a cohort of 30-day ICH survivors, consecutively admitted from January 2002 to July 2014, to assess whether the use of statins after the acute event is associated with recurrent cerebral bleeding. Results 1623 patients (mean age, 73.910.3 years; males, 55.9%) qualified for the analysis. After a median follow-up of 40.5 months (25th to 75th percentile, 67.7) statin use was not associated with increased risk of recurrent ICH either in the whole study group (adjusted HR, 0.99; 95%CI 0.64 to 1.53) or in the subgroups defined by haematoma location (deep ICH, adjusted HR, 0.74; 95%CI 0.35 to 1.57; lobar ICH, adjusted HR, 1.09; 95%CI 0.62 to 1.90), intensity of statins (low-moderate intensity statins, adjusted HR, 0.93; 95%CI 0.58 to 1.49; high-intensity statins, adjusted HR, 1.48; 95%CI 0.66 to 3.31) and use of statins before the index event (adjusted HR, 0.66; 95%CI 0.38 to 1.17). Conclusions Statin use appears to be unrelated to the risk of ICH recurrence.

Endovascular treatment (EVT) is recommended for acute ischemic stroke due to large-vessel occlusion (LVO) and an ASPECTs ≥ 6. Recent randomized controlled trials (RCTs) have become available on effect of EVT in patients with LVO-related large core infarct stroke (ASPECTS 0–5). We conducted a systematic review and meta-analysis of trials on patients with large core infarct treated with thrombectomy compared to best medical therapy (BMT). The study followed PRISMA guidelines. Primary endpoint was functional independence at 90 days (modified Rankin Scale mRS < 3). Secondary endpoints were 3-month moderate disability (mRS < 4), excellent outcome (mRS < 2) and change in mRS (shift analysis). Safety outcomes were: symptomatic intracranial hemorrhage (sICH) and 3-month mortality. Seven RCTs were included with a total of 1964 patients. Functional independence was significantly more frequent in EVT vs BMT group (19.4

Background/Objectives: Endovascular treatment (EVT) is recommended for acute ischemic stroke due to large-vessel occlusion (LVO) and an Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6. Randomized controlled trials (RCTs) have recently become available on EVT effects in people with LVO-related large core stroke (ASPECTS 0–5). Here, we provide an updated meta-analysis of the EVT effect on functional neurological status in people with large-core stroke. Methods: The study followed the PRISMA guidelines. PubMed, EMBASE and Cochrane Central were searched for RCTs comparing EVT vs. best medical treatment (BMT) in large-core LVO stroke. The primary outcome was functional independence at 90 days (modified Rankin Scale; mRS 0–2). The secondary outcomes were symptomatic intracranial hemorrhage (sICH), good functional outcome (mRS 0–3) and excellent functional outcome (mRS 0–1). EVT vs. BMT was compared through random effect meta-analysis. Heterogeneity was assessed with the I2 and Q test and risk of bias reported according to the RoB2 tool. Results: Six RCTs were included (n = 1656 patients). All studies had a moderate risk of bias, with blinding bias due to the nature of the intervention, potential allocation bias and incomplete outcome reporting. Functional independence was significantly more frequent in the EVT vs. BMT group (OR = 2.47, 95% CI = 1.52–4.03, p < 0.001). sICH rates (OR = 1.77, 95% CI = 1.01–3.11, p = 0.04) and good functional outcome (OR = 2.20; 95% CI = 1.72–2.81, p < 0.001) were more frequent in the EVT vs. BMT group, while the rates of mRS 0–1 did not differ. Conclusions: In patients with large-core stroke and LVO, EVT plus BMT as compared to BMT alone carries a significant increase in independent ambulation and good functional outcome at 3 months despite the marginal increase in sICH.

Introduction: It is unclear which patients with non-traumatic (spontaneous) intracerebral haemorrhage (ICH) are at risk of developing acute symptomatic seizures (provoked seizures occurring within the first week after stroke onset; early seizures, ES) and whether ES predispose to the occurrence of remote symptomatic seizures (unprovoked seizures occurring more than 1 week after stroke; post-stroke epilepsy, PSE) and long-term mortality.Patients and Methods: In the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) we examined the risk of ES and whether they predict the occurrence of PSE and all-cause mortality in a cohort of patients with first-ever spontaneous ICH and no previous history of epilepsy, consecutively hospitalized in 12 Italian neurological centers from 2002 to 2014.Results: Among 2570 patients (mean age, 73.4 +/- 12.5 years; males, 55.4%) 228 (8.9%) had acute ES (183 (7.1%) short seizures and 45 (1.8%) status epilepticus (SE)). Lobar location of the hematoma (OR, 1.49; 95% CI, 1.06-2.08) was independently associated with the occurrence of ES. Of the 2,037 patients who were followed-up (median follow-up time, 68.0 months (25th-75th percentile, 77.0)), 155 (7.6%) developed PSE. ES (aHR, 2.34; 95% CI, 1.42-3.85), especially when presenting as short seizures (aHR, 2.35; 95% CI, 1.38-4.00) were associated to PSE occurrence. Unlike short seizures, SE was an independent predictor of all-cause mortality (aHR, 1.50; 95% CI, 1.005-2.26).Discussion and Conclusion: The long-term risk of PSE and death after an ICH vary according to ES subtype. This might have implications for the design of future clinical trials targeting post-ICH epileptic seizures. Graphical abstract

Interpretation Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. Findings In 2019, 273 center dot 9 million (95% uncertainty interval 258 center dot 5 to 290 center dot 9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4 center dot 72% (4 center dot 46 to 5 center dot 01). 228 center dot 2 million (213 center dot 6 to 244 center dot 7; 83 center dot 29% [82 center dot 15 to 84 center dot 42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global agestandardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1 center dot 21% [-1 center dot 26 to -1 center dot 16]), similar progress was not observed for chewing tobacco (0 center dot 46% [0 center dot 13 to 0 center dot 79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0 center dot 94% [-1 center dot 72 to -0 center dot 14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Summary Background Chewing tobacco and other types of smokeless tobacco use have had less attention from the global health community than smoked tobacco use. However, the practice is popular in many parts of the world and has been linked to several adverse health outcomes. Understanding trends in prevalence with age, over time, and by location and sex is important for policy setting and in relation to monitoring and assessing commitment to the WHO Framework Convention on Tobacco Control. Methods We estimated prevalence of chewing tobacco use as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 using a modelling strategy that used information on multiple types of smokeless tobacco products. We generated a time series of prevalence of chewing tobacco use among individuals aged 15 years and older from 1990 to 2019 in 204 countries and territories, including age-sex specific estimates. We also compared these trends to those of smoked tobacco over the same time period. Findings In 2019, 273 & middot;9 million (95% uncertainty interval 258 & middot;5 to 290 & middot;9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4 & middot;72% (4 & middot;46 to 5 & middot;01). 228 & middot;2 million (213 & middot;6 to 244 & middot;7; 83 & middot;29% [82 & middot;15 to 84 & middot;42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global age standardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1 & middot;21% [-1 & middot;26 to -1 & middot;16]), similar progress was not observed for chewing tobacco (0 & middot;46% [0 & middot;13 to 0 & middot;79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0 & middot;94% [-1 & middot;72 to -0 & middot;14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Interpretation Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. Copyright (c) 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Background The effect of the COVID pandemic on stroke network performance is unclear, particularly with consideration of drip&ship vs. mothership models. Aims We systematically reviewed and meta-analyzed variations in stroke admissions, rate and timing of reperfusion treatments during the first wave COVID pandemic vs. the pre-pandemic timeframe depending on stroke network model adopted. Summary of findings The systematic review followed registered protocol (PROSPERO-CRD42020211535), PRISMA and MOOSE guidelines. We searched MEDLINE, EMBASE, and CENTRAL until 9 October 2020 for studies reporting variations in ischemic stroke admissions, treatment rates, and timing in COVID (first wave) vs. control-period. Primary outcome was the weekly admission incidence rate ratio (IRR = admissions during COVID-period/admissions during control-period). Secondary outcomes were (i) changes in rate of reperfusion treatments and (ii) time metrics for pre- and in-hospital phase. Data were pooled using random-effects models, comparing mothership vs. drip&ship model. Overall, 29 studies were included in quantitative synthesis (n = 212,960). COVID-period was associated with a significant reduction in stroke admission rates (IRR = 0.69, 95%CI = 0.61–0.79), with higher relative presentation of large vessel occlusion (risk ratio (RR) = 1.62, 95% confidence interval (CI) = 1.24–2.12). Proportions of patients treated with endovascular treatment increased (RR = 1.14, 95%CI = 1.02–1.28). Intravenous thrombolysis decreased overall (IRR = 0.72, 95%CI = 0.54–0.96) but not in the mothership model (IRR = 0.81, 95%CI = 0.43–1.52). Onset-to-door time was longer for the drip&ship in COVID-period compared to the control-period (+32 min, 95%CI = 0–64). Door-to-scan was longer in COVID-period (+5 min, 95%CI = 2–7). Door-to-needle and door-to-groin were similar in COVID-period and control-period. Conclusions Despite a 35% drop in stroke admissions during the first pandemic wave, proportions of patients receiving reperfusion and time-metrics were not inferior to control-period. Mothership preserved the weekly rate of intravenous thrombolysis and the onset-to-door timing to pre-pandemic standards.

Background and Purpose: Coronavirus disease 2019 (CO­VID-19) infection is an ongoing pandemic and worldwide health emergency that has caused important changes in healthcare systems. Previous studies reported an increased risk of thromboembolic events, including stroke. This systematic review aims to describe the clinical features and etiological characteristics of ischemic stroke patients with CO­VID-19 infection. Method: A literature search was performed in principal databases for studies and case reports containing data concerning risk factors, clinical features, and etiological characteristics of patients infected with COVID-19 and suffering from stroke. Descriptive and analytical statistics were applied. Results: Overall, 14 articles were included for a total of 93 patients. Median age was 65 (IQR: 55–75) years with prevalence in males. Stroke occurred after a median of 6 days from COVID-19 infection diagnosis. Median National of Institute of Health Stroke Scale (NIHSS) score was 19. Cryptogenic (Cry) strokes were more frequent (51.8%), followed by cardioembolic etiology, and they occurred a long time after COVID-19 diagnosis compared with large-artery atherosclerosis strokes (ptrend: 0.03). The clinical severity of stroke was significantly associated with the severity grade of COVID-19 infection (ptrend: 0.03). Conclusions: Ischemic strokes in COVID-19-infected patients were clinically severe, affecting younger patients mainly with Cry and cardioembolic etiologies. Further multicenter prospective registries are needed to better describe the causal association and the effect of COVID-19 infection on stroke.

Background and Aims: The effect of the COVID pandemic on stroke networks performance are unclear, particularly with consideration of drip & ship versus mothership models. We systematically reviewed and metaanalyzed variations in stroke admissions, rate and timing of reperfusion treatments during the COVID pandemic versus the prepandemic timeframe. Methods: The systematic review followed registered protocol (PROSPERO-CRD42020211535), PRISMA and MOOSE guidelines. We searched MEDLINE, EMBASE and Cochrane CENTRAL until 9/10/ 2020, for studies reporting variations in ischemic stroke admissions, treatment rates and timing in COVID vs control-period. Primary outcome was the weekly admission incidence rate ratio (IRR=admissions during COVID-period/admissions during control-period). Secondary outcomes were (i) changes in rate of patients undergoing reperfusion treatment and (ii) time metrics for pre-and in-hospital phase. Results: Twenty-nine studies were included in qualitative synthesis, with 212960 patients observed for 532 cumulative weeks (325 control-period, 207 COVID-period). COVID-period was associated with a significant reduction in stroke admission rates (IRR=0.69, 95%CI, 0.61-0.79) and a higher relative presentation with large vessel occlusion stroke (RR=1.62, 95%CI, 1.24-2.12). Proportions of patients treated with intravenous thrombolysis remained unchanged, while endovascular treatment increased (RR=1.14, 95%CI, 1.02-1.28). Onset-to-door time was longer for drip&ship compared to mothership model (+32 minutes vs-12 minutes, pmeta-regression =.03). Conclusions: Despite a 35% drop in stroke admissions during the pandemic, proportions of patients receiving reperfusion and time-metrics were not inferior to control-period, justifying allocation of resources to keep stroke networks up and running.

BACKGROUND:Mechanical thrombectomy (MT) is effective in treating ischemic strokes due to large vessel occlusion. However, the risk-benefit ratio of intravenous thrombolysis (IVT) prior to MT is still unclear. Aim of the study was to provide a pooled analysis of only randomized controlled trials (RCTs) comparing direct MT (dMT) vs bridging treatment (IVT+MT). METHODS:PubMed, EMBASE and Cochrane Central were searched only for RCTs comparing IVT+MT vs dMT in ischemic stroke patients. Primary endpoint was functional independence at 90 days (mRS<3), while secondary endpoints were represented by successful recanalization (TICI>2a), mortality at 90 days and symptomatic intracranial hemorrhage (sICH). Odds ratios for endpoints were pooled with meta-analysis and compared between reperfusion strategies. RESULTS:The pooled analysis comprised 5 studies (n. patients = 1657). The rates for the primary endpoint were 39% and 34.5% for dMT and IVT+MT, respectively (OR 1.06; 95%CI 0.80-1.40). For the secondary endpoints, we did not observe significant differences between groups, even if the rate of successful recanalization was higher in IVT+MT treated patients (OR: 0.58; 95%CI 0.26-1.30;pheterogeneity = 0.002), without a significant increase in sICH rates (4.3% vs 5.5%; OR: 0.96; 95%CI 0.43-2.13;pheterogeneity = 0.26). Finally, mortality rates were 19.8% and 15.9% for dMT and IVT+MT, respectively. CONCLUSIONS:In this meta-analysis including only RCTs, dMT and bridging treatment were substantially equivalent for good functional outcome. IVT+MT was associated to higher rates of successful recanalization, even if not significant. Therefore, further adequately powered RCTs comparing dMT vs IVT+MT are warranted.

Dementia is currently one of the leading causes of mortality globally, and mortality due to dementia will likely increase in the future along with corresponding increases in population growth and population aging. However, large inconsistencies in coding practices in vital registration systems over time and between countries complicate the estimation of global dementia mortality.

During the coronavirus disease 2019 (COVID-19) outbreak, a decrease of stroke’s hospital admissions and reperfusion therapy has been reported worldwide. This retrospective observational study assessed the volume of stroke cases managed in the Emergency Department (ED) and reperfusion therapies in an Italian stroke network with a high incidence of COVID-19, particularly to evaluate if the in-hospital rerouting and the switch from a drip-and-ship to a mothership model could assure an adequate volume of acute treatments. We compared data from March 2020 with those from previous years and formulated five PICO questions regarding (1) incidence of stroke cases in the ED; (2) relation between stroke cases and COVID-19; (3) differences in the number of reperfusion therapies, (4) in the call-to-needle and door-to-needle times for intravenous thrombolysis, and (5) in the call-to-groin and door-to-groin times for thrombectomy. We found (1) a 28% decreased of confirmed stroke cases managed in the ED, (2) a negative correlation between stroke cases in ED and COVID-19 progression (rs = − .390, p = .030), and (3) a similar number of treatments in March 2020 and March 2019. The adoption of the mothership model (4) did not delay alteplase infusion (median call-to-needle p = .126, median door-to-needle p = .142) but led to (5) a significant reduction in median call-to-groin (p = .018) and door-to-groin times (p = .010). The “hospital avoidance” of stroke patients during the “stay-at-home” appeals needs to be considered for future public health campaigns. A prompt reorganization of the stroke network can guarantee optimal performances at times of crisis.

Introduction Despite intravenous thrombolysis (IVT) and endovascular treatment (EVT) have been demonstrated effective in acute ischemic stroke (AIS) due to large vessel occlusions, there are still no conclusive data to guide treatment in stroke due to cervical internal carotid artery (ICA) occlusion. We systematically reviewed available literature to compare IVT, EVT, and bridging (IVT + EVT) and define optimal treatment. Methods Systematic review followed predefined protocol (Open-Science-Framework osf.io/bfykj ). MEDLINE, EMBASE, and Cochrane CENTRAL were searched. Results were restricted to studies in English, with sample size ≥ 10 and follow-up ≥30 days. Primary outcomes were favorable outcome (mRS ≤ 2), mortality, and symptomatic intracerebral hemorrhage(sICH), defined according to study original report. Newcastle-Ottawa scale was used for bias assessment. Results Seven records of 930 screened were included in meta-analysis. Quality of studies was low-to-fair in 5, good in 2. IVT ( n = 450) did not differ for favorable outcome and mortality compared to EVT ( n = 150), though having lower rate of sICH (OR = 0.4, 95% CI 0.2–0.8). Compared to IVT, bridging (IVT + EVT) was associated with higher rate of favorable outcome (OR = 2.2, 95% CI 1.3–3.7). Compared to EVT, bridging (IVT + EVT) provided higher rate of favorable outcome (OR = 1.9, 95% CI 1.1–3.4), with a marginally increased risk of sICH (OR = 2.1, 95% CI 1–4.4) but similar mortality rates. Conclusions Our systematic review highlights that, in acute ischemic stroke associated with isolated cervical ICA occlusion, bridging (IVT + EVT) might lead to higher rate of functional independence at follow-up, without increasing mortality. The low quality of available studies prevents from drawing firm conclusions, and randomized-controlled clinical trials are critically needed to define optimal treatment in this AIS subgroup.

Background and Purpose Substantial uncertainty exists on the benefit of organizational paradigms in stroke networks. Here we systematically reviewed and meta-analyzed data from studies comparing functional outcome between the mothership (MS) and the drip and ship (DS) models.Methods The meta-analysis protocol was registered international prospective register of systematic reviews (PROSPERO) and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, and Cochrane Central databases were searched for randomized-controlled clinical trials (RCTs), retrospective and prospective studies comparing MS versus DS. Primary endpoints were functional independence at 90 days (modified Rankin Scale <3) and successful recanalization (Thrombolysis in Cerebral Infarction Scale [TICI] >2a); secondary endpoints were 3-month mortality and symptomatic intracranial haemorrhage (sICH). Odds ratios for endpoints were pooled using the random effects model and were compared between the two organizational models.Results Overall, 18 studies (n=7,017) were included in quantitative synthesis. MS paradigm was superior to DS model for functional independence (odds ratio, 1.34; 95% confidence interval, 1.16 to 1.55; I2=30%). Meta-regression analysis revealed association between onset-to-needle time and good functional outcome, with longer onset-to-needle time being detrimental. Similar rates of recanalization, sICH and mortality at 90 days were documented between MS and DS.Conclusions Patients with acute ischemic stroke eligible for reperfusion strategies might benefit more from MS paradigm as compared to DS. RCTs are needed to further refine best management taking into account logistics, facilities and resources.

Cervicocerebral artery dissection (CAD) is one of the more frequent causes of stroke in young adults with rates of up to 25%. Predisposing and risk factors for CAD are very different, and an etiological classification is based on the presence of a previous minor or major trauma, differentiating traumatic from spontaneous CAD. Headache represents one of the main initial symptoms for this pathological condition, probably due to the release of pro-inflammatory neurotransmitters from nerve terminals near the injured vessel. For its peculiar characteristics, the headache due to CAD has been defined with specific ICHD-3 criteria. In many cases, headache is associated with other signs related to the dissection or cerebral ischemia. In this systematic review of literature, headache was reported in more than 70% of cases with CAD with a prevalence in vertebrobasilar dissections. More than half of patients suffered a severe pain that was usually located in fronto-temporal and occipito-nuchal regions in the case of dissections in the anterior and posterior circulation, respectively. For the high stroke risk, CAD has to be promptly diagnosed with MRI or CTA and treated with anticoagulants or antithrombotics.

Stroke is a major health-care problem that represents a leading cause of death and also the top cause of disability in adulthood. In recent years there has been a significant paradigm shift in treatments for acute ischemic stroke to favor earlier reperfusion therapy, mainly using the systemic infusion of recombinant tissue plasminogen activator. Subsequent trials found that combining this treatment with endovascular therapy was effective in selected patients. The increased complexity of acute stroke treatments has resulted in a substantial reorganization of stroke care. This review reports on the evolution of acute ischemic stroke treatment and describes the main organizational models based on the hub-and-spoke system. The lack of evidence for comparisons of the effectiveness of different paradigms means that some decision-analysis models predicting the best organizational pathways are also reported, with a particular emphasis on the workflow timing in the prehospital and in-hospital settings. Major benchmarks and performance measures are also reported, focusing on the timing of interventions and rates of process indicators. Finally, future directions are illustrated, including using telemedicine for stroke, mobile stroke units, and artificial intelligence and automated machines to produce software for detecting large-vessel occlusion.

Objective To report on efficacy and safety of intravenous immunoglobulin (IVIg) therapy in a case series of patients with COVID-19-related encephalopathy. Methods We retrospectively collected data on all patients with COVID-19 hospitalized at two Italian hospitals who developed encephalopathy during disease course and were treated with IVIg. Results Five patients (two females, mean age 66.8 years) developed encephalopathy after a mean of 12.6 days, since the onset of respiratory/constitutional symptoms related to COVID-19. Four patients suffered severe respiratory distress, three of which required invasive mechanical ventilation. Neurological manifestations included impaired consciousness, agitation, delirium, pyramidal and extrapyramidal signs. EEG demonstrated diffuse slowing in all patients. Brain MRI showed non-specific findings. CSF analysis revealed normal cell count and protein levels. In all subjects, RT-PCR for SARS-CoV-2 in CSF tested negative. IVIg at 0.4 g/kg/die was commenced 29.8 days (mean, range: 19–55 days) after encephalopathy onset, leading to complete electroclinical recovery in all patients, with an initial improvement of neuropsychiatric symptoms observed in 3.4 days (mean, range: 1–10 days). No adverse events related to IVIg were observed. Conclusions Our preliminary findings suggest that IVIg may represent a safe and effective treatment for COVID-19-associated encephalopathy. Clinical efficacy may be driven by the anti-inflammatory action of IVIg, associated with its anti-cytokine qualities.

Background and Aim: The risk/benefit profile of intravenous thrombolysis (IVT) prior to endovascular thrombectomy (EVT) in acute ischemic stroke is still unclear. We provide a systematic review and meta-analysis including studies comparing direct EVT (dEVT) vs. bridging treatment (IVT + EVT), defining the impact of treatment timing and eligibility to IVT on functional status and mortality. Methods: Protocol was registered with PROSPERO (CRD42019135915) and followed PRISMA guidelines. PubMed, EMBASE, and Cochrane Central were searched for randomized controlled trials (RCTs), retrospective, and prospective studies comparing IVT + EVT vs. dEVT in adults (≥18) with acute ischemic stroke. Primary endpoint was functional independence at 90 days (modified Rankin Scale <3); secondary endpoints were (i) good recanalization (thrombolysis in cerebral infarction >2a), (ii) mortality, and (iii) symptomatic intracranial hemorrhage (sICH). Subgroup analysis was performed according to study type, eligibility to IVT, and onset-to-groin timing (OGT), stratifying studies for similar OGT. ORs for endpoints were pooled with meta-analysis and compared between reperfusion strategies. Results: Overall, 35 studies were included (n = 9,117). No significant differences emerged comparing patients undergoing dEVT and bridging treatment for gender, hypertension, diabetes, National Institute of Health Stroke Scale score at admission. Regarding primary endpoint, IVT + EVT was superior to dEVT (OR 1.44, 95% CI 1.22–1.69, p < 0.001, pheterogeneity<0.001), with number needed to treat being 18 in favor of IVT + EVT. Results were confirmed in studies with similar OGT (OR 1.66; 95% CI 1.21–2.28), shorter OGT for IVT + EVT (OR 1.53, 95% CI 1.27–1.85), and independently from IVT eligibility (OR 1.53, 95% CI 1.29–1.82). Mortality at 90 days was higher in dEVT (OR 1.38; 95% CI 1.09–1.75), but no significant difference was noted for sICH. However, considering data from RCT only, reperfusion strategies had similar primary (OR 0.91, 95% CI 0.6–1.39) and secondary endpoints. Differences in age and clinical severity across groups were unrelated to the primary endpoint. Conclusions: Compared to dEVT, IVT + EVT associates with better functional outcome and lower mortality. Post hoc data from RCTs point to substantial equivalence of reperfusion strategies. Therefore, an adequately powered RCTs comparing dEVT versus IVT + EVT are warranted.

Background Through a comprehensive analysis of Italy's estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we aimed to understand the patterns of health loss and response of the health-care system, and offer evidence-based policy indications in light of the demographic transition and government health spending in the country. Methods Estimates for Italy were extracted from GBD 2017. Data on Italy are presented for 1990 and 2017, on prevalence, causes of death, years of life lost, years lived with disability, disability-adjusted life-years (DALYs), life expectancy at birth and at age 65 years, healthy life expectancy, and Healthcare Access and Quality (HAQ) Index. We compared the estimates for Italy with those of 15 other western European countries. Findings The quality of the universal health system and healthy behaviours contribute to favourable overall health, even in comparison with other western European countries. In 2017, life expectancy and HAQ Index score in Italy were among the highest globally, with life expectancy at birth reaching 85.3 years for females and 80.8 for males in 2017, ranking Italy eighth globally for females and sixth for males, and an HAQ Index score of 94.9 in 2016 compared with 81.54 in 1990, keeping Italy ranked as ninth globally. Between 1990 and 2017 age-standardised death rates for cardiovascular diseases decreased by 53.7% (95% uncertainty interval -56.1 to -51.4), for neoplasms decreased by 28.2% (-32.3 to -24.6), and for transport injuries decreased by 62.1% (-64.6 to -59.2). However, population ageing is causing an increase in the burden of specific diseases, such as Alzheimer's disease and other dementias (DALYs increased by 77.9% [68.4 to 87.2]) and pancreatic (DALYs increased by 39.7% [28.4 to 51.7]) and uterine cancers (DALYs increased by 164.7% [129.7 to 202.5]). Behavioural risk factors, which are potentially modifiable, still have a strong effect, particularly on cardiovascular diseases and neoplasms. For instance, in 2017, 44 400 (41 200 to 47 800) cancer deaths were attributed to smoking, 12 000 (9600 to 14 800) to alcohol use, and 9500 (5400 to 14 200) to high body-mass index, while 47 000 (31 100 to 65 700) deaths due to cardiovascular diseases could be attributed to high LDL cholesterol, 28 700 (19 700 to 38 500) to diets low in whole grains, and 15 900 (8500 to 24 900) to low physical activity. Interpretation Italy provides an interesting example of the results that can be achieved by a mix of relatively healthy lifestyles and a universal health system. Two main issues require attention, population ageing and gradual decrease of public health financing, which both pose several challenges to the future of Italy's health status. Our findings should be useful to Italy's policy makers and health system experts elsewhere. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.

Introduction: The aim of this study was to prospectively investigate the occurrence of early poststroke seizures (within 7 days of stroke) in patients undergoing reperfusion therapies (intravenous rtPA [recombinant tissue plasminogen activator] and/or endovascular thrombectomy) in comparison to those not undergoing these procedures. Methods: Patients aged >= 18 years with acute ischemic stroke admitted in five Italian centers were prospectively recruited. Clinical data, details on stroke type and etiology, stroke treatment, and radiological datawere collected. The frequency of early poststroke seizures was assessed, and predictive factors for their occurrence were evaluated. Results: Five hundred and sixteen patients (262 in the reperfusion therapies group) were included. Stroke severity on admission and at discharge was higher among patients undergoing reperfusion therapies. Ten patients (3.8%) undergoing reperfusion therapies and 6 (2.3%) of those not receiving these treatments experienced early poststroke seizures (p= 0.45). Therewere no differences in any of the baseline characteristics between patients experiencing and those not experiencing early seizures. Conclusion: The incidence of early poststroke seizureswas overall rare, and no significant differences emerged between patients receiving and those not receiving reperfusion therapies. (C) 2019 Elsevier Inc. All rights reserved.