Detection of atrial fibrillation after stroke due to large or small vessel disease: systematic review and meta-analysis.

BACKGROUND: Emerging evidence indicates a frequent occurrence of atrial fibrillation (AF) detection among patients with established causes of ischemic stroke unrelated to AF. This systematic review and meta-analysis aimed to evaluate AF detection rates in stroke patients with large or small vessel disease, considering the AF detection modality and duration of cardiac rhythm monitoring. AIMS: We conducted a comprehensive search of PubMed and Scopus databases up to March 2, 2024, to identify randomized controlled trials, non-randomized prospective studies, and retrospective studies assessing the frequency of AF detection in stroke patients with large or small vessel disease. The primary outcome of interest was the rate of AF detection. We utilized inverse-variance weights to produce the pooled prevalence (effect size-ES) and 95% confidence interval (CI) of patients diagnosed with post-stroke AF. SUMMARY OF REVIEW: In the analysis of 14 eligible studies encompassing 4,334 patients, AF was identified in 154 out of 2,082 patients with strokes attributed to small or large-vessel disease, yielding a pooled prevalence of 6.27% (ES; 95% confidence interval [CI]: 3.18-10.17, I2=87.83%). Among patients with large-vessel disease strokes, AF was diagnosed in 79 out of 1,042 patients, accounting for a pooled prevalence of 5.07% (ES;95% CI: 1.30-10.33, I2=77.05%). Similarly, among those with small-vessel disease strokes, AF was detected in 75 out of 1,040 patients, with a pooled prevalence of 5.03% (ES; 95% CI: 1.96-9.06, I2=78.05%). CONCLUSIONS: AF is often found in ischemic stroke patients with large or small-vessel disease. Detection rates increase with longer cardiac rhythm monitoring. The safety and benefits of oral anticoagulation for these AF episodes are uncertain.

Characteristics and outcomes of atrial fibrillation detected before and after acute ischemic stroke.

BACKGROUND: Atrial fibrillation (AF) can be known before the stroke (KAF) or be newly detected after stroke (AFDAS). It is unknown whether the outcome of stroke differs between KAF and AFDAS. We performed a propensity-matched analysis to investigate the outcome of patients with AFDAS and their counterparts with KAF. METHODS: We analysed a consecutive series of patients enrolled into the EIDASAF study, a single centre, retrospective study of ischemic stroke patients with a diagnosis of AF before or after the event who had been admitted to the Hyperacute Stroke Unit of Imperial College Healthcare NHS Trust between 2010 and 2017. RESULTS: Overall, our cohort included 959 patients with AF and acute ischemic stroke. After propensity score matching, 547 patients were matched (404 KAF group and 143 AFDAS group). The rates of in hospital death and of haemorrhagic transformation were significantly higher in KAF patients compared to AFDAS patients. Logistic regression analysis did not reveal a statistically significant influence of AF subtypes on the outcome of death. However, in logistic regression analysis KAF was associated with increased probability of haemorrhagic transformation (OR 9.64; CI 1.29-71.68, p = 0.022) after the index event. CONCLUSION: KAF is associated with an increased risk of haemorrhagic transformation but not of death when compared to AFDAS.

Mechanical Thrombectomy in Ischemic Stroke with a Large Infarct Core: A Meta-Analysis of Randomized Controlled Trials.

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.

Endovascular Treatment for Basilar Artery Occlusion.

Basilar artery occlusion (BAO) is a neurological emergency associated with a high risk for adverse outcomes. This review provides evidence on the therapeutic efficacy of intravenous thrombolysis (IVT) and endovascular therapy (EVT) in the treatment of BAO. Historically considered the primary intervention for acute ischemic stroke, IVT has been progressively combined with EVT, which has emerged from recent studies demonstrating clinical benefits, notably in patients presenting with severe stroke. Several randomised controlled trials have shown that EVT improves patient outcomes in select clinical contexts. Future research directions could address therapeutic treatment thresholds, combination strategies, and long-term outcomes.

Safety and Outcomes of Mechanical Thrombectomy in Acute Ischemic Stroke Attributable to Cardiological Diseases: A Scoping Review.

There is limited evidence on the outcomes and safety of mechanical thrombectomy (MT) among patients with acute ischemic stroke (AIS) in the context of cardiac diseases. Our study reviews MT in AIS within the context of cardiac diseases, aiming to identify existing and emerging needs and gaps. PubMed and Scopus were searched until December 31, 2023, using a combination of cardiological diseases and "mechanical thrombectomy" or "endovascular treatment" as keywords. Study design included case reports/series, observational studies, randomized clinical trials, and meta-analyses/systematic reviews. We identified 943 articles, of which 130 were included in the review. Results were categorized according to the cardiac conditions. MT shows significant benefits in patients with atrial fibrillation (n=139) but lacks data for stroke occurring after percutaneous coronary intervention (n=2) or transcatheter aortic valve implantation (n=5). MT is beneficial in AIS attributable to infective endocarditis (n=34), although functional benefit may be limited. Controversy surrounds the functional outcomes and mortality of patients with AIS with heart failure undergoing MT (n=11). Despite technical challenges, MT appears feasible in aortic dissection cases (n=4), and in patients with left ventricular assist device or total artificial heart (n=10). Data on AIS attributable to congenital heart disease (n=4) primarily focus on pediatric cases requiring technical modifications. Treatment outcomes of MT in patients with cardiac tumors (n=8) vary because of clot consistency differences. After cardiac surgery stroke, MT may improve outcomes with early intervention (n=13). Available data outline the feasibility of MT in patients with AIS attributable to large-vessel occlusion in the context of cardiac diseases.

Predictors of futile recanalization in nonagenarians treated with mechanical thrombectomy: a multi-center observational study.

BACKGROUND: There is a lack of data regarding patients aged 90 years or older undergoing mechanical thrombectomy and their predictors of futile recanalization. AIMS: We sought to evaluate the predictors of futile recanalization in patients ≥ 90 years with large vessel occlusion undergoing mechanical thrombectomy. METHODS: This multi-center observational retrospective study included patients ≥ 90 years consecutively treated with mechanical thrombectomy in four thrombectomy capable centers between January 1st, 2016 and 30th March 2023. Futile recanalization was defined as large vessel occlusion patients experiencing a 90-day poor outcome (mRS 3-6) despite successful recanalization (mTICI ≥ 2b) after mechanical thrombectomy. RESULTS: Our cohort included 139 patients ≥ 90 years with acute ischemic stroke due to anterior circulation large vessel occlusion treated with mechanical thrombectomy. One hundred seventeen of one hundred thirty-nine patients ≥ 90 years who achieved successful recanalization were included in the analysis (seventy-six female (64.9%)), of whom thirty-one (26.49%) experienced effective recanalization and eighty-six (73.51%) experienced futile recanalization. Patients with futile recanalization had higher NIHSS on admission (p < 0.001); they were less frequently treated with intravenous thrombolysis (p = 0.048), had more often general anesthesia (p = 0.011), and longer door to groin puncture delay (p = 0.002). Univariable regression analysis showed that use of intravenous thrombolysis (0.29, 95% CI 0.02-0.79, p = 0.034) and site of occlusion distal vs proximal (0.34, 95% CI 0.11-0.97, p = 0.044) were associated with reduced probability of futile recanalization while NIHSS on admission (1.29, 95% CI 1.16-1.45, p < 0.001), NIHSS at 24 h (1.15, 95% CI 1.07-1.25, p = 0.002), type of anesthesia used (4.18, 95% CI 1.57-11.08, p = 0.004), and door to groin puncture time (1.02, 95% CI 1.00-1.05, p = 0.005) were associated with increased probability of futile recanalization. Multivariable regression analysis showed that use of intravenous thrombolysis (0.44, 95% CI 0.09-0.88, p = 0.039) was associated with reduced probability of futile recanalization. CONCLUSION: Our study seems to suggest that mechanical thrombectomy with intravenous thrombolysis is associated with reduced probability of futile recanalization in a multi-center cohort of patients aged 90 years or older.

Stress hyperglycemia is associated with futile recanalization in patients with anterior large vessel occlusion undergoing mechanical thrombectomy.

INTRODUCTION: Mechanical thrombectomy (MT) is the standard treatment for acute ischemic stroke (AIS) due to anterior large vessel occlusion (LVO). Despite successful recanalization, some patients remain disabled after 3 months. Mechanisms that can cause futile recanalization (FR) are still largely unknown. We investigated if stress hyperglycemia might be associated with FR. PATIENTS AND METHODS: This is a retrospective analysis of consecutive patients with successful recanalization treated in four participating centers between January 2021 and December 2022. According to the modified Rankin scale (mRS) status at 3 months, patients were divided into two groups: FR, if mRS score >2, and useful recanalization (UR), if mRS score ⩽2. Stress hyperglycemia was estimated by the glucose-to-glycated hemoglobin ratio (GAR) index. RESULTS: A total of 691 subjects were included. At 3 months, 403 patients (58.3%) were included in the FR group, while the remaining 288 patients (41.7%) were included in the UR group. At the multivariate analysis, variables independently associated with FR were the following: age (OR 1.04, 95% CI 1.02-1.06, p < 0.001), GAR index (OR 1.08, 95% CI 1.03-1.14, p = 0.003), NIHSS at admission (OR 1.16, 95% CI 1.11-1.22; p < 0.001), and procedure length (OR 1.01, 95% CI 1.00-1.02; p = 0.009). We observed that the model combining age, GAR index, NIHSS at admission, and procedure length had good predictive accuracy (AUC 0.78, 95% CI 0.74-0.81). CONCLUSIONS: Stress hyperglycemia predicts FR in patients with successful recanalization after MT. Further studies should explore if managing stress hyperglycemia may reduce futile recanalization. Additionally, we recommend paying close attention to AIS patients with a GAR index greater than 24.8 who exhibit a high risk of FR.

Posterior reversible encephalopathy syndrome associated with antibiotic therapy: a case report and systematic review.

Posterior reversible encephalopathy syndrome (PRES) is an acute neurological condition associated with different etiologies, including antibiotic therapy. To date, most data regarding antibiotic-related PRES are limited to case reports and small case series. Here, we report a novel case description and provide a systematic review of the clinico-radiological characteristics and prognosis of available cases of PRES associated with antibiotic therapy. We performed a systematic literature search in PubMed and Scopus from inception to 10 January 2024, following PRISMA guidelines and a predefined protocol. The database search yielded 12 subjects (including our case). We described the case of a 55-year-old female patient with PRES occurring one day after administration of metronidazole and showing elevated serum neurofilament light chain protein levels and favorable outcome. In our systematic review, antibiotic-associated PRES was more frequent in female patients (83.3%). Metronidazole and fluoroquinolones were the most reported antibiotics (33.3% each). Clinical and radiological features were comparable to those of PRES due to other causes. Regarding the prognosis, about one third of the cases were admitted to the intensive care unit, but almost all subjects (90.0%) had a complete or almost complete clinical and radiological recovery after prompt cessation of the causative drug. Antibiotic-associated PRES appears to share most of the characteristics of classic PRES. Given the overall good prognosis of the disease, it is important to promptly diagnose antibiotic-associated PRES and discontinue the causative drug.

Predictors of atrial fibrillation detection in embolic stroke of undetermined source patients with implantable loop recorder.

Background: Covert atrial fibrillation (AF) is a predominant aetiology of embolic stroke of undetermined source (ESUS). Evidence suggested that AF is more frequently detected by implantable loop recorder (ILR) than by conventional monitoring. However, the predictive factors associated with occult AF detected using ILRs are not well established yet. In this study we aim to investigate the predictors of AF detection in patients with ESUS undergoing an ILR. Methods: This observational multi-centre study included consecutive ESUS patients who underwent ILR implantation. The infarcts were divided in deep, cortical infarcts or both. The infarction sites were categorized as anterior and middle cerebral artery, posterior cerebral artery with and without brainstem/cerebellum involvement. Multivariable logistic regression analysis was performed to investigate variables associated with AF detection. Results: Overall, 3,000 patients were initially identified. However, in total, 127 patients who consecutively underwent ILR implantation were included in our analysis. AF was detected in 33 (26%) out of 127 patients. The median follow-up was 411 days. There were no significant differences in clinical characteristics and comorbidities between patients with and without AF detected. AF was detected more often after posterior cerebral artery infarct with brainstem/cerebellum involvement (p < 0.001) whereas less often after infarction in the anterior and middle cerebral artery (p = 0.021). Multivariable regression analysis demonstrated that posterior cerebral artery infarct with brainstem/cerebellum involvement was an independent predictor of AF detection. Conclusion: Our study showed that posterior circulation infarcts with brainstem/cerebellum involvement are associated with AF detection in ESUS patients undergoing ILR. Larger prospective studies are needed to validate our findings.

Risk of stroke with different levels of leisure-time physical activity: a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Leisure-time physical activity (LTPA) protects against vascular diseases. Whether and to what extent different levels of LTPA, including lower ones, benefit stroke prevention is still unclear. METHODS: We searched prospective cohort studies, indexed on PubMed and Scopus, published in English up to 22 April 2023, that investigated, in a general healthy population, the relationship between different predefined LTPA levels, compared with inactivity, and the risk of any type of stroke. We applied random effect modelling for meta-analyses and meta-regression to control for the impact of age and sex. RESULTS: Out of 3064 screened articles, 15 articles on 16 cohorts of subjects were included in meta-analyses, with a total of 752 050 followed-up subjects. Mean follow-up was 125.7±77.5 months. Included studies identified three (none, below target and ideal) to five (none, insufficient, low, moderate and intense) levels of LTPA. In the five studies identifying three levels of LTPA, compared with no LTPA, below target (risk ratio (RR)=0.82, 95% CI=0.75 to 0.88) and ideal LTPA significantly reduced stroke risk (RR=0.71, 95% CI=0.58 to 0.86).Lower levels of LTPA also mitigated stroke risk in studies reporting on four (n=6; RR=0.73, 95% CI=0.62 to 0.87 favouring moderate LTPA over no LTPA) and five levels (n=2; RR=0.71, 95% CI=0.58 to 0.88 favouring moderate LTPA over no LTPA). The benefits of LTPA were independent of age and sex. CONCLUSIONS: According to our results, all levels of LTPA can be beneficial for stroke prevention, including levels currently regarded as low or insufficient. People should be encouraged to be physically active even at the lowest levels. PROSPERO REGISTRATION NUMBER: CRD42023425302.

Sex Differences in the Epidemiology of Intracerebral Hemorrhage Over 10 Years in a Population-Based Stroke Registry.

BACKGROUND: We investigated incidence and outcome of spontaneous intracerebral hemorrhage (ICH) in a population-based stroke registry and provided data to inform on the figures of the disease in women and in men. METHODS AND RESULTS: Our prospective population-based registry included patients with first-ever ICH occurring from January 2011 to December 2020. Incidence rates were standardized to the 2011 Italian and European population, and incidence rate ratios were calculated. Multivariate hazard ratios for 30-day and 1-year fatality were estimated with Cox regression, including components of the ICH score and sex. We included 748 first-ever ICHs (41.3% women). Women were significantly older than men at ICH onset (78.9±12.6 versus 73.2±13.6 years; P<0.001) and showed higher clinical severity on presentation (median National Institutes of Health Stroke Scale score, 11 [interquartile range, 6-20] versus 9 [interquartile range, 4-15], respectively; P=0.016). The crude annual incidence rate was 20.2 (95% CI, 18.0-22.6) per 100 000 person-years in women and 30.2 (95% CI, 27.4-33.2) per 100 000 person-years in men); incidence was lower in women versus men (incidence rate ratio, 0.67 [95% CI, 0.58-0.78]; P<0.001) and did not change over time in both sexes (P for trend=0.073 and 0.904, respectively). Unadjusted comparison showed higher 1-year case-fatality rates in women versus men (48.5% versus 40.1%; P=0.026). After adjusting for components of the ICH score, female sex lost significance as a predictor of mortality. CONCLUSIONS: We found lower ICH incidence in women than in men. However, women showed a higher 1-year case-fatality rate versus men, which was likely related to older age at ICH onset and higher clinical severity. Identification of factors explaining the reported differences is important to develop targeted interventions.

Safety and outcomes of different endovascular treatment techniques for anterior circulation ischaemic stroke in the elderly: data from the Imperial College Thrombectomy Registry.

BACKGROUND: Although previous studies investigated the main predictors of outcomes after endovascular thrombectomy (EVT) in patients aged 80 years and older, less is known about the impact of the procedural features on outcomes in elderly patients. The aim of this study was to investigate the influence of EVT technical procedures on the main 3-month outcomes in a population of patients aged 80 years and older. METHODS: This observational, prospective, single-centre study included consecutive patients with acute LVO ischaemic stroke of the anterior circulation. The study outcomes were functional independence at 3 months after EVT (defined as a mRS score of 0-2), successful reperfusion (mTICI ≥ 2b), incidence of haeamorrhagic transformation, and 90-day all cause of mortality. RESULTS: Our cohort included 497 patients with acute ischaemic stroke due to LVO treated with EVT. Among them, 105 (21.1%) patients were aged ≥ 80 years. In the elderly group, multivariable regression analysis showed that thromboaspiration technique vs stent-retriever was the single independent predictor of favourable post-procedural TICI score (OR = 7.65, 95%CI = 2.22-26.32, p = 0.001). CONCLUSIONS: Our study suggests that EVT for LVO stroke in the elderly could be safe. The use of thromboaspiration was associated with positive reperfusion outcome in this population. Further studies in larger series are warranted to confirm the present results and to evaluate the safety and efficacy of EVT in the elderly and oldest adults.

Outcomes of mechanical thrombectomy in acute stroke patients with atrial fibrillation detected after stroke versus known atrial fibrillation.

We aim to compare the outcomes in patients with atrial fibrillation detected after stroke (AFDAS) and their counterparts with known AF (KAF) presenting with large vessel occlusion (LVO) treated with mechanical thrombectomy (MT). This observational, prospective study included consecutive patients with acute LVO ischemic stroke of the anterior circulation with AFDAS, KAF and without AF. The primary study outcome was functional independence at 90 days after stroke. The secondary study outcomes were variation of the NIHSS score at 24 h, rate of successful reperfusion, death at 90 days and rate of immediate complications post-procedure. Overall, our cohort included 518 patients with acute ischemic stroke and LVO treated with MT, with 289 (56.8%) without a diagnosis of AF; 107 (21%) with AFDAS; 122 (22.2%) with KAF. There was no significant difference in terms of functional independence at 90 days after stroke between the three groups. Regarding the secondary study outcome, the rate of symptomatic intracranial haemorrhage (sICH) and/or parenchymal hematoma (PH) were significantly higher in the group of patients without AF (respectively, P = 0.030 and < 0.010). Logistic regression analysis showed that the subtypes of AF were not statistically significantly associated with functional independence at 90 days after stroke and with the likelihood of any ICH. Our results suggest that the subtypes of AF are not associated with clinical and safety outcomes of MT in patients with acute stroke and LVO. Further studies are needed to confirm our findings.

Advances in mechanical thrombectomy for acute ischaemic stroke.

Mechanical thrombectomy is a ground breaking treatment for acute ischaemic stroke caused by occlusion of a large vessel. Its efficacy over intravenous thrombolysis has been proven in multiple trials with a lower number needed to treat than percutaneous coronary intervention for acute myocardial infarction. However, access to this key treatment modality remains limited with a considerable postcode lottery across the UK and many parts of the world. The evidence base for mechanical thrombectomy dates back to 2015. Since then, there have been important advances in establishing and widening the criteria for treatment. This narrative review aims to summarise the current evidence base and latest advances for physicians and academics with an interest in recanalisation treatments for acute ischaemic stroke.

Outcomes of mechanical thrombectomy in orally anticoagulated patients with anterior circulation large vessel occlusion: a propensity-matched analysis of the Imperial College Thrombectomy Registry.

BACKGROUND: Mechanical thrombectomy (MT) remains an effective treatment for patients with acute ischemic stroke receiving oral anticoagulation (OAC) and large vessel occlusion (LVO). However, to date, it remains unclear whether MT is safe in patients on treatment with OAC. AIMS: In our study, we performed a propensity-matched analysis to investigate the safety and efficacy of MT in patients with acute ischemic stroke receiving anticoagulants. A propensity score method was used to target the causal inference of the observational study design. METHODS: This observational, prospective, single-centre study included consecutive patients with acute LVO ischemic stroke of the anterior circulation. Demographic, neuro-imaging and clinical data were collected and compared according to the anticoagulation status at baseline, patients on OAC vs those not on OAC. The primary study outcomes were the occurrence of any intracerebral haemorrhage (ICH) and symptomatic ICH. The secondary study outcomes were functional independence at 90 days after stroke (defined as modified Rankin Scale (mRS) scores of 0 through 2), mortality at 3 months and successful reperfusion rate according to the modified treatment in cerebral infarction (mTICI) score. RESULTS: Overall, our cohort included 573 patients with acute ischemic stroke and LVO treated with MT. After propensity score matching, 495 patients were matched (99 OAC group vs 396 no OAC group). There were no differences in terms of clinical characteristics between the two groups, except for the rate of intravenous thrombolysis less frequently given in the OAC group. There was no significant difference in terms of the rate of any ICH and symptomatic ICH between the two groups. With regards to the secondary study outcome, there was no significant difference in terms of the rate of successful recanalization post-procedure and functional independence at 3 months between the two groups. Patients in the OAC group showed a reduced mortality rate at 90 days compared to the patients with no previous use of anticoagulation (20.2% vs 21.2%, p = 0.031). Logistic regression analysis did not reveal a statistically significant influence of the anticoagulation status on the likelihood of any ICH (OR = 0.95, 95% CI = 0.46-1.97, p = 0.900) and symptomatic ICH (OR = 4.87, 95% CI = 0.64-37.1, p = 0.127). Our analysis showed also that pre-admission anticoagulant use was not associated with functional independence at 90 days after stroke (OR = 0.76, 95% CI = 0.39-1.48, p = 0.422) and rate of successful reperfusion (OR = 0.81, 95% CI = 0.38-1.72, p = 0.582). CONCLUSION: According to our findings anticoagulation status at baseline did not raise any suggestion of safety and efficacy concerns when MT treatment is provided according to the standard guidelines. Confirmation of these results in larger controlled prospective cohorts is necessary.

Prognostic performance of blood neurofilament light chain protein in hospitalized COVID-19 patients without major central nervous system manifestations: an individual participant data meta-analysis.

BACKGROUND AND AIMS: To investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19). METHODS: We conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd 2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU) admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL. RESULTS: We identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2 ± 15.0 years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13-3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with a higher likelihood of ICU admission, need of MV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need of MV and ICU admission, respectively. CONCLUSIONS: Blood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19.

Time course of neuroinflammation after human stroke - a pilot study using co-registered PET and MRI.

BACKGROUND: Microglial activation contributes to both inflammatory damage and repair in experimental ischemic stroke. However, because of the logistical challenges, there have been few clinical imaging studies directly describing inflammatory activation and its resolution after stroke. The purpose of our pilot study was to describe the spatio-temporal profile of brain inflammation after stroke using 18kD translocator protein (TSPO) positron emission tomography (PET) with magnetic resonance (MR) co-registration in the subacute and chronic stage after stroke. METHODS: Three patients underwent magnetic resonance imaging (MRI) and PET scans with TSPO ligand [11C]PBR28 15 ± 3 and 90 ± 7 days after an ischaemic stroke. Regions of interest (ROI) were defined on MRI images and applied to the dynamic PET data to derive regional time-activity curves. Regional uptake was quantified as standardised uptake values (SUV) over 60 to 90 min post-injection. ROI analysis was applied to identify binding in the infarct, and in frontal, temporal, parietal, and occipital lobes and cerebellum excluding the infarcted area. RESULTS: The mean age of participants was 56 ± 20.4 years and mean infarct volume was 17.9 ± 18.1 ml. [11C]PBR28 showed increased tracer signal in the infarcted area compared to non-infarcted areas of the brain in the subacute phase of stroke (Patient 1 SUV 1.81; Patient 2 SUV 1.15; Patient 3 SUV 1.64). [11C]PBR28 uptake returned to the level of non-infarcted areas at 90 days Patient 1 SUV 0.99; Patient 3 SUV 0.80). No additional upregulation was detected elsewhere at either time point. CONCLUSIONS: The neuroinflammatory reaction after ischaemic stroke is limited in time and circumscribed in space suggesting that post-ischaemic inflammation is tightly controlled but regulatory mechanisms.

Endovascular Thrombectomy with or without Intravenous Thrombolysis for Anterior Circulation Large Vessel Occlusion in the Imperial College London Thrombectomy Registry.

Background and purpose. Mechanical thrombectomy (MT) is the standard of care for eligible patients with a large vessel occlusion (LVO) acute ischemic stroke. Among patients undergoing MT there has been uncertainty regarding the role of intravenous thrombolysis (IVT) and previous trials have yielded conflicting results regarding clinical outcomes. We aim to investigate clinical, reperfusion outcomes and safety of MT with or without IVT for ischemic stroke due to anterior circulation LVO. Materials and Methods. This observational, prospective, single-centre study included consecutive patients with acute LVO ischemic stroke of the anterior circulation. The primary outcomes were the rate of in-hospital mortality, symptomatic intracranial haemorrhage and functional independence (mRS 0-2 at 90 days). Results. We enrolled a total of 577 consecutive patients: 161 (27.9%) were treated with MT alone while 416 (72.1%) underwent IVT and MT. Patients with MT who were treated with IVT had lower rates of in-hospital mortality (p = 0.037), higher TICI reperfusion grades (p = 0.007), similar rates of symptomatic intracranial haemorrhage (p = 0.317) and a higher percentage of functional independence mRS (0-2) at 90 days (p = 0.022). Bridging IVT with MT compared to MT alone was independently associated with a favorable post-intervention TICI score (>2b) (OR, 1.716; 95% CI, 1.076-2.735, p = 0.023). Conclusions. Our findings suggest that combined treatment with MT and IVT is safe and results in increased reperfusion rates as compared to MT alone.

The multifaceted role of neurofilament light chain protein in non-primary neurological diseases.

The advancing validation and exploitation of CSF and blood neurofilament light chain protein as a biomarker of neuroaxonal damage has deeply changed the current diagnostic and prognostic approach to neurological diseases. Further, recent studies have provided evidence of potential new applications of this biomarker also in non-primary neurological diseases. In the present review we summarize the state of the art, future perspectives, but also limitations, of neurofilament light chain protein as a CSF and blood biomarker in several medical fields, including intensive care medicine, surgery, internal medicine and psychiatry. In particular, neurofilament light chain protein is associated with the degree of neurological impairment and outcome in patients admitted to intensive care units or in the perioperative phase and it seems to be highly interconnected with cardiovascular risk factors. Beyond that, interesting diagnostic and prognostic insights have been provided by the investigation of neurofilament light chain protein in psychiatric disorders as well as in the current coronavirus disease-19 pandemic and in normal ageing. Altogether, current data outline a multifaceted applicability of CSF and blood neurofilament light chain protein ranging from the critical clinical setting to the development of precision medicine models suggesting a strict interplay between the nervous system pathophysiology and the health-illness continuum.