Statin use and long-term risk of recurrent intracerebral haemorrhage: the MUCH-Italy.

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, 73.9±10.3 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.

Early seizures and risk of epilepsy and death after intracerebral haemorrhage: The MUCH Italy.

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.

Stroke network performance during the first COVID-19 pandemic stage: A meta-analysis based on stroke network models.

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.

Risk Factors, and Clinical and Etiological Characteristics of Ischemic Strokes in COVID-19-Infected Patients: A Systematic Review of Literature.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (CO-VID-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 CO-VID-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.

Endovascular treatment versus intravenous thrombolysis alone in isolated M2 occlusion: a meta-analysis.

BACKGROUND: Optimal reperfusion strategies for M2 occlusion are still uncertain, with previous studies questioning benefit of mechanical thrombectomy (MT) over intravenous thrombolysis alone (IVT). Here we systematically reviewed and meta-analyzed data from studies comparing IVT alone vs MT with/without previous IVT, to define risk/benefit profile of each paradigm. METHODS: The study followed PRISMA guidelines. PubMed, EMBASE, and Cochrane Central were searched only for RCTs comparing MT with or without IVT vs IVT alone in adults with acute ischemic stroke and M2 occlusion. Primary endpoint was functional independence at 90 days (modified Rankin Scale<3); secondary endpoints were represented by symptomatic intracranial hemorrhage (sICH) and good recanalization (TICI>2a). Odds ratios for endpoints were pooled with meta-analysis and compared between reperfusion strategies. RESULTS: Seven studies (n=779) were included, all of high quality. Rate of good functional outcome was similar for MT and IVT (62.4% vs 66.3%; OR=0.73; 95%CI: 0.38-1.41; pheterogeneity=0.008) (Fig. 1).sICH was significantly more frequent in the MT group (8.5%) vs IVT group (3%) (OR 2.76, 95%CI 1.19-6.36, pheterogeneity=0.14). Good recanalization (TICI>2a) rate was higher in MT group vs IVT alone group (81.2% vs 51.4%; OR 3.99; 95%CI: 1.98-8.94; pheterogeneity=0.80). CONCLUSIONS: IVT alone provides similar clinical benefit compared to MT with/without IVT in cases of M2 occlusion. MT quadruplicates rates of good recanalization, but triplicates risk of sICH. Further trials are needed to define if MT confers any advantage over IVT for M2 occlusion.

Mechanical thrombectomy with or without thrombolysis: A meta-analysis of RCTs.

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.

Impact of COVID-19 pandemic on acute stroke care: facing an epidemiological paradox with a paradigm shift.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Reperfusion strategies in stroke due to isolated cervical internal carotid artery occlusion: systematic review and treatment comparison.

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.

Intravenous immunoglobulin therapy in COVID-19-related encephalopathy.

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.

Mothership versus Drip-and-Ship Model for Mechanical Thrombectomy in Acute Stroke: A Systematic Review and Meta-Analysis for Clinical and Radiological Outcomes.

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.

Headache in cervicocerebral artery dissection.

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.

Organizing Healthcare for Optimal Acute Ischemic Stroke Treatment.

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.

Bridging versus Direct Mechanical Thrombectomy in Acute Ischemic Stroke: A Subgroup Pooled Meta-Analysis for Time of Intervention, Eligibility, and Study Design.

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.

Incidence of early poststroke seizures during reperfusion therapies in patients with acute ischemic stroke: An observational prospective study: (TESI study: "Trombolisi/Trombectomia e crisi Epilettiche precoci nello Stroke Ischemico").

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 data were 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). There were no differences in any of the baseline characteristics between patients experiencing and those not experiencing early seizures. CONCLUSION: The incidence of early poststroke seizures was overall rare, and no significant differences emerged between patients receiving and those not receiving reperfusion therapies. This article is part of the Special Issue "Seizures and Stroke".

The Large ARtery Intracranial Occlusion Stroke Scale: A New Tool With High Accuracy in Predicting Large Vessel Occlusion.

Objectives: The combination of systemic thrombolysis and mechanical thrombectomy is indicated in patients with ischemic stroke due to a large vessel occlusion (LVO) and these treatments are time-dependent. Rapid identification of patients with suspected LVO also in a prehospital setting could influence the choice of the destination hospital. Aim of this pilot study was to evaluate the predictive role of a new stroke scale for LVO, comparing it to other scores. Patients and Methods: All consecutive patients admitted to our comprehensive stroke center with suspected ischemic stroke were studied with a CT angiography and 5 different stroke scales were applied. The Large ARtery Occlusion (LARIO) stroke scale consists of 5 items including the assessment of facial palsy, language alteration, grip and arm weakness, and the presence of neglect. A Receiving Operating Characteristic curve was evaluated for each stroke scale to explore the level of accuracy in LVO prediction. Results: A total of 145 patients were included in the analysis. LVO was detected in 37.2% of patients. The Area Under Curve of the LARIO score was 0.951 (95%CI: 0.902-0.980), similar to NIHSS and higher than other scales. The cut-off score for best performance of the LARIO stroke scale was higher than 3 (positive predictive value: 77% and negative predictive value: 100%). Conclusion: The LARIO stroke scale is a simple tool, showing high accuracy in detecting LVO, even if with some limitations due to some false positive cases. Its efficacy has to be confirmed in a pre-hospital setting and other centers.

Patent Foramen Ovale Closure Versus Medical Therapy in Cryptogenic Strokes and Transient Ischemic Attacks: A Meta-Analysis of Randomized Trials.

Cryptogenic strokes account for about 25% to 40% of total ischemic strokes, and 1 of the 3 of these have a patent foramen ovale (PFO). A meta-analysis concerning the effectiveness and safety of PFO closure in cryptogenic strokes or transient ischemic attacks (TIAs) was performed. We systematically searched Medline, Embase, and the Cochrane Library through April 2018. Eligible studies were randomized clinical trials. Primary and secondary end points were, respectively, stroke or TIA and stroke recurrences. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for all end points using fixed- and random-effects meta-analyses. Data were included from 6 trials involving 3560 patients. In the pooled analysis, PFO closure was superior to medical treatment for both primary (RR: 0.39; 95% CI: 0.18-0.82; P < .02) and secondary end points (RR: 0.58; 95% CI: 0.44-0.76; P < .001). Transcatheter closure significantly increased the risk of new-onset atrial fibrillation (AF; RR: 5.74; P < .001). Percutaneous closure is superior to medical treatment in reducing stroke and TIA recurrence, even if with a significant risk increasing for new-onset AF. These findings suggest that transcatheter closure is indicated in patients with cryptogenic strokes and large PFO.

Mechanical Thrombectomy in Strokes with Large-Vessel Occlusion Beyond 6 Hours: A Pooled Analysis of Randomized Trials.

BACKGROUND AND PURPOSE: Mechanical thrombectomy with or without intravenous thrombolysis is indicated in the acute treatment of ischemic strokes caused by an emergent large-vessel occlusion (ELVO) within 6 hours from symptom onset. However, a significant proportion of patients are referred to comprehensive stroke centers beyond this therapeutic time window. This study performed a pooled analysis of data from trials in which mechanical thrombectomy was performed beyond 6 hours from symptom onset. METHODS: We searched for randomized controlled trials that compared mechanical thrombectomy with the best medical treatment beyond 6 hours for ischemic strokes due to ELVO and reported on between 1990 and April 2018. The intervention group comprised patients treated with mechanical thrombectomy. Statistical analysis was conducted while pooling data and analyzing fixed- or random-effects models as appropriate. RESULTS: Four trials involving 518 stroke patients met the eligibility criteria. There were 267 strokes treated with mechanical thrombectomy, with a median time of 10.8 hours between when the patient was last known to be well to randomization. We observed a significant difference between groups concerning the rate of functional independence at 90 days from stroke, with an absolute difference of 27.5% (odds ratio=3.33, 95% CI=1.81-6.12, p<0.001) and good recanalization (odds ratio=13.17, 95% CI=4.17-41.60, p<0.001) favoring the intervention group. CONCLUSIONS: This meta-analysis confirms the efficacy of mechanical thrombectomy in selected ischemic stroke patients beyond 6 hours from symptom onset. The selection is mainly based on the limited core infarct detected by emergent assessment using neuroimaging techniques.

Ambient air pollution and cardiovascular diseases: From bench to bedside.

Air pollution has a great impact on health, representing one of the leading causes of death worldwide. Previous experimental and epidemiological studies suggested the role of pollutants as risk factors for cardiovascular diseases. For this reason, international guidelines included specific statements regarding the contribution of particulate matter exposure to increase the risk of these events. In this review, we summarise the main evidence concerning the mechanisms involved in the processes linking air pollutants to the development of cardiovascular diseases.

The organisation of the acute ischemic stroke management: key notes of the Italian Neurological Society and of the Italian Stroke Organization.

The main aim of acute ischemic stroke treatment is the as much possible prompt, safe and effective arterial recanalisation, in order to restore reperfusion into the ischemic brain area. The procedures obtaining this result are rapidly evolving and in the last years, we observed new evidences that affirmed the therapeutical benefit of the concomitant treatment using endovenous thrombolysis and mechanical thrombectomy in selected patients with ischemic stroke. However, all treatments are time-sensitive and the main limitation for their application is represented by the time. For this reason, the optimisation of the acute stroke management that includes a pre-hospital and an in-hospital phase is essential to reduce the avoidable delay, increasing the number of patients potentially treatable. The purpose of this document is to define the main elements and to suggest the principal key points constituting the optimal pathway of stroke management in Italian care settings, in line with the recommendations coming from the current national and international guidelines.

Infections and Chlamydia pneumoniae antibodies influence the functional outcome in thrombolysed strokes.

OBJECTIVE: Thrombolysis is effective in ischemic stroke patients, but some factors influence its benefit. Previous infections could increase the risk of ischemic stroke by an activation of systemic inflammation. We analysed the influence of previous infections and Chlamydia pneumoniae serology on functional outcome in thrombolysed stroke patients. METHODS: Consecutive thrombolysed stroke patients admitted during calendar year 2011 were analysed. Demographics, vascular risk factors, clinical and aetiological data were registered. Standardised blood tests were collected acutely for each patient, including inflammatory factors. Primary outcome was the functional outcome at 6months follow-up. t-test, Mann-Withney U test and chi-square test were applied for univariate analysis, while a logistic regression was performed for multivariate analysis. RESULTS: A total of 142 patients were included in the analysis. Median onset-to-needle time was 156min. A previous infection occurred in 16.9% of patients, while a positive IgA antiChlamydia was detected in 40 cases. Good functional outcome was achieved by 72.5% of patients. At multivariate analysis poor outcome was associated to clinical severity, delay treatment time, haemorrhagic transformation and large artery etiological stroke type (p<0.01). Also IgA antiChlamydia pneumonia seropositivity (OR: 3.699; 95%CI: 1.094-12.512; p: 0.035) and poststroke infections (OR: 6.031; 95%CI: 2.485-11.301; p: 0.037) were predictors of poor outcome. INTERPRETATION: In this study IgA antiChlamydia pneumonia seropositivity represents a negative predictor of functional outcome in thrombolysed stroke patients. Further and larger studies are required to confirm these observations and to plan a prompt administration of antibiotics or immunomodulant agents.