Plasma Brain-Derived Tau in Prognosis of Large Vessel Occlusion Ischemic Stroke.

BACKGROUND: Large vessel occlusion acute ischemic stroke prognosis improved following the 2015 endovascular therapy (EVT) trials. Blood-based biomarkers may improve outcome prediction. We aimed to assess plasma brain-derived tau (BD-Tau) performance in predicting post-EVT large vessel occlusion acute ischemic stroke outcomes. METHODS: We included 2 temporally independent prospective cohorts of anterior circulation in patients with large vessel occlusion acute ischemic stroke who successfully recanalized post-EVT. We measured plasma BD-Tau, GFAP (glial-fibrillary-acidic-protein), NfL (neurofilament-light-chain), and total-Tau upon admission, immediately, 24 hours, and 72 hours post-EVT. Twenty-four-hour neuroimaging and 90-day functional outcomes were independently assessed using the Alberta Stroke Program Early Computed Tomography Score (good outcome: >7 or unchanged) and the modified Rankin Scale (favorable outcome <3 or unchanged), respectively. Based on the first cohort (derivation), we built a multivariable logistic regression model to predict a 90-day functional outcome. Model results were evaluated using the second cohort (evaluation). RESULTS: In the derivation cohort (n=78, mean age=72.9 years, 50% women), 62% of patients had a good 24-hour neuroimaging outcome, and 45% had a favorable 90-day functional outcome. GFAP admission-to-EVT rate-of-change was the best predictor for early neuroimaging outcome but not for 90-day functional outcome. At admission, BD-Tau levels presented the highest discriminative performance for 90-day functional outcomes (area under the curve, 0.76 [95% CI, 0.65-0.87]; P<0.001). The model incorporating age, admission BD-Tau, and 24-hour Alberta Stroke Program Early Computed Tomography Score achieved excellent discrimination of 90-day functional outcome (area under the curve, 0.89 [95% CI, 0.82-0.97]; P<0.001). The score's predictive performance was maintained in the evaluation cohort (n=66; area under the curve, 0.82 [95% CI, 0.71-0.92]; P<0.001). CONCLUSIONS: Admission plasma BD-Tau accurately predicted 90-day functional outcomes in patients with large vessel occlusion acute ischemic stroke after successful EVT. The proposed model may predict functional outcomes using objective measures, minimizing human-related biases and serving as a simplified prognostic tool for AIS.

Early plasma biomarker dynamic profiles are associated with acute ischemic stroke outcomes.

BACKGROUND: Early outcome prediction after acute ischemic stroke (AIS) might be improved with blood-based biomarkers. We investigated whether the longitudinal profile of a multi-marker panel could predict the outcome of successfully recanalized AIS patients. METHODS: We used ultrasensitive single-molecule array (Simoa) to measure glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), total-tau (t-tau) and ELISA for brevican in a prospective study of AIS patients with anterior circulation large vessel occlusion successfully submitted to thrombectomy. Plasma was obtained at admission, upon treatment, 24 h and 72 h after treatment. Clinical and neuroimaging outcomes were assessed independently. RESULTS: Thirty-five patients (64.8%) had good early clinical or neuroimaging outcome. Baseline biomarker levels did not distinguish between outcomes. However, longitudinal intra-individual biomarker changes followed different dynamic profiles with time and according to outcome. GFAP levels exhibited an early and prominent increase between admission and just after treatment. NfL increase was less pronounced between admission and up to 24 h. T-tau increased between treatment and 24 h. Interestingly, GFAP rate-of-change (pg/ml/h) between admission and immediately after recanalization had a good discriminative capacity between clinical outcomes (AUC = 0.88, p < 0.001), which was higher than admission CT-ASPECTS (AUC = 0.75, p < 0.01). T-tau rate-of-change provided moderate discriminative capacity (AUC = 0.71, p < 0.05). Moreover, in AIS patients with admission CT-ASPECTS <9 both GFAP and NfL rate-of-change were good outcome predictors (AUC = 0.82 and 0.77, p < 0.05). CONCLUSION: Early GFAP, t-tau and NfL rate-of-change in plasma can predict AIS clinical and neuroimaging outcome after successful recanalization. Such dynamic measures match and anticipate neuroimaging predictive capacity, potentially improving AIS patient stratification for treatment, and targeting individualized stroke care.

Posterior Circulation Stroke: Coma (More Than Time) is Brain.

BACKGROUND AND PURPOSE: Contrary to anterior circulation, the legitimacy of endovascular treatment in posterior circulation stroke is still being questioned. Finding reliable prognostic factors and determining how patient selection should be done has become top priority. METHODS: Observational and retrospective study from two Portuguese hospitals, including all consecutive patients with posterior circulation occlusions who underwent thrombectomy between January 1st 2015 and December 31st 2019. RESULTS: Out of a total of 126 patients, the median age was 74 (IQR 61-80) and 39.7% were female. A good clinical outcome (mRS ≤2) was associated with a lower incidence of coma (24,2% vs 66,7%, p < 0,001) and of sudden onset coma (3% vs 18%,=0,04), a lower NIHSS at admission (14 vs 19, p < 0,001), a higher pc-ASPECTS at admission (10 vs 9, p < 0,001) and at 24 h (8 vs 6, p < 0,001) and a higher BATMAN score (7 vs 6, p = 0,017). Differences in the times of symptom-onset-to-recanalization (496 vs 536, p = 0,19) and symptom-onset-to-coma (130 vs 195, p = 0,52) were not remarkable. When excluding NIHSS and pc-ASPECTS at 24 h, coma (p = 0,003; OR=0,22; 95% CI: 0,08-0,59) and the pc-ASPECTS at admission (p = 0,037; OR=1,63; 95% CI: 1,03-2,57) become independent predictors of good outcome. CONCLUSIONS: In strokes from the posterior circulation, coma, more than time, appears to be an important prognostic factor. The BATMAN and the pc-ASPECTS scores were also associated with clinical outcome and coma.

Periprocedural Myocardial Infarction After Carotid Endarterectomy and Stenting: Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Carotid angioplasty and stenting (CAS) is associated with higher risk of periprocedural stroke and death when compared with carotid endarterectomy (CEA). By contrast, the risk of myocardial infarction (MI) was higher after CEA than after CAS in randomized trials. However, numbers were small, and risk factors are unknown. METHODS: We performed a systematic review and a meta-analysis of studies published from January 1980 to June 2014 and collected unpublished data. We extracted data on 9 predefined risk factors (age, contralateral carotid occlusion, coronary artery disease, diabetes mellitus, sex, hypertension, peripheral artery disease, type stenosis, and clinical presentation). We selected studies with data available on MI in at least 1 subgroup, calculated absolute and relative risks, and identified differential effects on risks of MI. RESULTS: The 30-day absolute risk of MI was 0.87% (95% confidence interval, 0.69-1.07) after CEA and 0.70% (95% confidence interval, 0.54-0.88) after CAS (Pint=0.38). After CAS, patients with symptomatic stenosis and restenosis were at higher risk of MI, whereas men were at lower risk. After CEA, age, history of coronary artery disease, peripheral artery disease, and restenosis increased the risk of MI. Only the effect of sex differed between CAS and CEA with men being at lower risk of MI than women after CAS, whereas there was no difference between after CEA (Pint=0.01). CONCLUSIONS: The risk of MI after CEA and CAS did not significantly differ. Risk factors for MI are overall similar in both techniques except that men are at lower risk of MI after CAS but not after CEA.

Long-term prognosis of patients presenting first-ever vestibular symptoms in a community-based study.

BACKGROUND: Vestibular symptoms (VSs) are frequent complaints in patients attending ambulatory care and the emergency room. They may represent a peripheral vestibular disorder or a stroke/transient ischemic attack (TIA), yet many patients have VSs that cannot be clearly classified at presentation. This study aims to characterize and determine the long-term prognosis of these patients. METHODS: In a prospective community-based study involving 104,700 individuals registered at 4 health centers of Northern Portugal, patients with a first-ever-in-lifetime focal neurologic symptom (FNS) were ascertained using comprehensive methods, including referrals from physicians working in the study area and data retrieved from emergency/discharge records. Physicians were encouraged to report/notify any patient who might have experienced an FNS, including those with vertigo or vertigo-like symptoms, imbalance, presyncope, or nonspecific dizziness. After neurologic assessment patients were classified as having a peripheral vestibular symptom (pVS), a stroke/TIA, or an unclassified vestibular symptom (uVS). They were followed up 7 years after the index event at the outpatient clinic; predictors of survival free from stroke or vascular events were determined using Cox proportional hazards models. RESULTS: Of the 1163 patients with an FNS, 360 (31.0%) were included, 16.7% had a stroke/TIA, 57.8% had pVS, and 25.6% had uVS. Most patients presented only isolated VSs (62.8%); 63% were women and mean age was 60.1 years (standard deviation = 16); hypertension (47.8%), hypercholesterolemia (41.9%), and diabetes (19.2%) were the most prevalent vascular risk factors (VRFs). Cranial computed tomography (CT) scan was performed in 63.3%. Adjusting for age, sex, VRFs, and diagnosis (TIA, pVS and uVS), the long-term risk of stroke was higher when CT showed silent infarctions (hazard rate [HR] = 3.96; 95% confidence interval [CI], 1.63-9.60) and the risk of vascular events (stroke, myocardial infarction, or vascular death) was higher in patients with 2 or more VRFs (HR = 2.70; 95% CI, 1.25-5.86). Identical results were obtained when restricting the model to patients with pVS or uVS. CONCLUSIONS: First-ever-in-lifetime VSs are common in patients with FNS and may represent a good opportunity for preventing a serious vascular event, particularly in patients with vascular comorbidity (silent infarctions and VRFs).

A clinical rule (sex, contralateral occlusion, age, and restenosis) to select patients for stenting versus carotid endarterectomy: systematic review of observational studies with validation in randomized trials.

BACKGROUND AND PURPOSE: Compared with carotid endarterectomy (CEA), carotid angioplasty and stenting (CAS) is associated with a higher risk of procedural stroke or death especially in patients with symptomatic stenosis. However, after the perioperative period, risk is similar with both treatments, suggesting that CAS could be an acceptable option in selected patients. METHODS: We performed systematic reviews of observational studies of procedural risks of CEA or CAS and extracted data on 9 predefined risk factors (age, contralateral carotid occlusion, coronary artery disease, diabetes mellitus, sex, hypertension, peripheral artery disease, and type and side of stenosis). We calculated pooled relative risks of procedural stroke or death. Factors with differential effects on risk of CAS versus CEA were identified by interaction tests and used to derive a rule. The rule was tested using individual patient data from randomized trials of CAS versus CEA from the Carotid Stenting Trialists' Collaboration (CSTC). RESULTS: We identified 170 studies. The effects of sex, contralateral occlusion, age, and restenosis (SCAR) on the procedural risk of stroke or death differed. Patients with contralateral occlusion or restenosis and women<75 years were at relatively low risk for CAS (SCAR negative), with all others being high risk (SCAR positive). Among the 3049 patients in the CSTC validation, 694 (23%) patients were SCAR negative. The pooled RR of procedural stroke and death with CAS versus CEA was 0.93 (0.49-1.77; P=0.83) in SCAR-negative and 2.41 (1.68-3.45; P<0.0001) in SCAR-positive patients (P [interaction]=0.05). CONCLUSIONS: The SCAR rule is potentially useful to identify patients in whom CAS has a similar risk of perioperative stroke or death to CEA.

Nationwide Access to Endovascular Treatment for Acute Ischemic Stroke in Portugal.

INTRODUCTION: Since the publication of endovascular treatment trials and European Stroke Guidelines, Portugal has re-organized stroke healthcare. The nine centers performing endovascular treatment are not equally distributed within the country, which may lead to differential access to endovascular treatment. Our main aim was to perform a descriptive analysis of the main treatment metrics regarding endovascular treatment in mainland Portugal and its administrative districts. MATERIAL AND METHODS: A retrospective national multicentric cohort study was conducted, including all ischemic stroke patients treated with endovascular treatment in mainland Portugal over two years (July 2015 to June 2017). All endovascular treatment centers contributed to an anonymized database. Demographic, stroke-related and procedure-related variables were collected. Crude endovascular treatment rates were calculated per 100 000 inhabitants for mainland Portugal, and each district and endovascular treatment standardized ratios (indirect age-sex standardization) were also calculated. Patient time metrics were computed as the median time between stroke onset, first-door, and puncture. RESULTS: A total of 1625 endovascular treatment procedures were registered. The endovascular treatment rate was 8.27/100 000 inhabitants/year. We found regional heterogeneity in endovascular treatment rates (1.58 to 16.53/100 000/year), with higher rates in districts closer to endovascular treatment centers. When analyzed by district, the median time from stroke onset to puncture ranged from 212 to 432 minutes, reflecting regional heterogeneity. DISCUSSION: Overall endovascular treatment rates and procedural times in Portugal are comparable to other international registries. We found geographic heterogeneity, with lower endovascular treatment rates and longer onset-to-puncture time in southern and inner regions. CONCLUSION: The overall national rate of EVT in the first two years after the organization of EVT-capable centers is one of the highest among European countries, however, significant regional disparities were documented. Moreover, stroke-onset-to-first-door times and in-hospital procedural times in the EVT centers were comparable to those reported in the randomized controlled trials performed in high-volume tertiary hospitals.

Introdução: A aprovação do tratamento endovascular para o acidente vascular cerebral isquémico obrigou à reorganização dos cuidados de saúde em Portugal. Os nove centros que realizam tratamento endovascular não estão distribuídos equitativamente pelo território, o que poderá causar acesso diferencial a tratamento. O principal objetivo deste estudo é realizar uma análise descritiva da frequência e métricas temporais do tratamento endovascular em Portugal continental e seus distritos. Material e Métodos: Estudo de coorte nacional multicêntrico, incluindo todos os doentes com acidente vascular cerebral isquémico submetidos a tratamento endovascular em Portugal continental durante um período de dois anos (julho 2015 a junho 2017). Foram colhidos dados demográficos, relacionados com o acidente vascular cerebral e variáveis do procedimento. Taxas de tratamento endovascular brutas e ajustadas (ajuste indireto a idade e sexo) foram calculadas por 100 000 habitantes/ano para Portugal continental e cada distrito. Métricas de procedimento como tempo entre instalação, primeira porta e punção foram também analisadas. Resultados: Foram registados 1625 tratamentos endovasculares, indicando uma taxa bruta nacional de tratamento endovascular de 8,27/100 000 habitantes/ano. As taxas de tratamento endovascular entre distritos variaram entre 1,58 e 16,53/100 000/ano, com taxas mais elevadas nos distritos próximos a hospitais com tratamento endovascular. O tempo entre sintomas e punção femural entre distritos variou entre 212 e 432 minutos. Discussão: A análise nacional a taxas de tratamento endovascular e tempos de atuação é comparável a outros registos internacionais. Verificaram-se heterogeneidades geográficas, com taxas de tratamento endovascular menores e maior tempo para tratamento nos distritos do sul e interior. Conclusão: Portugal continental apresenta uma taxa nacional de tratamento endovascular elevada, apresentando, contudo, assimetrias regionais no acesso. As métricas temporais foram comparáveis com as observadas nos ensaios clínicos piloto.

Transient ischemic attack: Incidence and early risk of stroke in northern Portugal from 1998-2000 to 2009-2011.

OBJECTIVE: A decline in TIA incidence would be expected mirroring stroke trends, but patient's awareness of symptoms/signs, improved diagnostic procedures and changes in severity of vascular disease may raise TIA incidence. We aimed to estimate changes in TIA incidence and 30-day stroke risk in Portugal. METHODS: Data from two prospective community-based registers of first-ever TIA in 104,700 (1998-2000) and 118,232 (2009-2011) persons were collected using comprehensive case ascertainment methods. Incidence and stroke risk from TIA onset were compared using different inception cohorts. ABCD2 was used to stratified stroke risk. RESULTS: Overall, 141 patients were included in 1998-2000 and 174 in 2009-2011. Crude annual incidence rate increased from 67 to 74/100,000 (IRR=1.12; 95% CI, 0.90-1.40), particularly in men under 65 years (IRR=1.79; 95% CI, 1.06-3.04). Male/female IRR increased from 1.20 (0.86-1.68) in 1998-2000 to 1.77 (1.31-2.39) in 2009-2011, after adjustment for age. Better control of vascular risk factors (VRFs) accounted for lower ABCD2 scores in 2009-2011. The 30-day stroke risk was similar in study periods (18.4% vs. 16.7%, p > 0.7), decreasing from 16.1% to 8.2% (p < 0.042) excluding patients reporting TIA after stroke occurrence and from 12.2% to 4.0% (p < 0.011) further excluding patients who had stroke in ambulance/hospital. ABCD2 discriminated stroke risk only in 1998-2000; stroke severity decreased while posterior circulation stroke was more common in 2009-2011. CONCLUSION: Despite a stable TIA incidence across periods, the risk increased in men compared to women. Better control of VRF accounted for lower ABCD2 scores and secondary prevention reduced stroke risk. Men under 65 years emerge as a preferential target for primary and secondary prevention.

Changes in stroke incidence, outcome, and associated factors in Porto between 1998 and 2011.

Objective Year 2000 marked a turning point in stroke prevention and treatment in Portugal. In face of high incidence rates stroke awareness campaigns, close surveillance of vascular risk factors and implementation of hospital stroke units were advanced by the National Health Authorities. To understand the effect of such measures, we assessed changes in stroke incidence and short-term outcome using data from two community-based registers undertaken in Porto in 1998-2000 and 2009-2011. Methods We used standard diagnostic criteria and multiple overlapping sources of case-ascertainment for first-ever strokes. Short-term outcome was measured by the modified Rankin Scale; disabling stroke was defined whenever post-stroke mRS score>pre-stroke mRS and >1. Results Globally, 462 and 405 first-ever stroke cases were registered in 1998-2000 and 2009-2011, respectively. Stroke incidence decreased by 23%, from 261 to 203/100,000 after adjustment for the Portuguese population. Significant reduction was found in those aged <75 years (31%) and in women (32%). Incidence of disabling strokes was reduced by 29%. Fatal strokes decreased by 46%, while intracerebral hemorrhage decreased by 51%. Risk of disability from stroke decreased by 11% (RR = 0.89; 95%CI, 0.81-0.98) in 2009-2011, as found after adjusting for patient/stroke characteristics in a Poisson model. Moreover, when patients arrived hospital within 3 h from stroke onset, the risk of disabling stroke was 0.76 (95%CI, 0.67-0.87) in 2009-2011 vs. 1998-2000, compared to 1.03 (95%CI, 0.89-1.12) for late arrival. Conclusion Risk of stroke, mainly of hemorrhagic stroke, was substantially reduced over time. Timely action in acute phase was responsible for the decline in disability across periods.