Atrial Fibrillation Detection and Load: Knowledge Gaps Related to Stroke Prevention.

Atrial fibrillation is a major cause of ischemic stroke. Technological advances now support prolonged cardiac rhythm monitoring using either surface electrodes or insertable cardiac monitors. Four major randomized controlled trials show that prolonged cardiac monitoring detects subclinical paroxysmal atrial fibrillation in 9% to 16% of patients with ischemic stroke, including in patients with potential alternative causes such as large artery disease or small vessel occlusion; however, the optimal monitoring strategy, including the target patient population and the monitoring device (whether to use an event monitor, insertable cardiac monitor, or stepped approach) has not been well defined. Furthermore, the clinical significance of very short duration paroxysmal atrial fibrillation remains controversial. The relevance of the duration of monitoring, burden of device-detected atrial fibrillation, and its proximity to the acute ischemic stroke will require more research to define the most effective methods for stroke prevention in this patient population.

Emergent Large Vessel Occlusion due to Intracranial Stenosis: Identification, Management, Challenges, and Future Directions.

This comprehensive literature review focuses on acute stroke related to intracranial atherosclerotic stenosis (ICAS), with an emphasis on ICAS-large vessel occlusion. ICAS is the leading cause of stroke globally, with high recurrence risk, especially in Asian, Black, and Hispanic populations. Various risk factors, including hypertension, diabetes, hyperlipidemia, smoking, and advanced age lead to ICAS, which in turn results in stroke through different mechanisms. Recurrent stroke risk in patients with ICAS with hemodynamic failure is particularly high, even with aggressive medical management. Developments in advanced imaging have improved our understanding of ICAS and ability to identify high-risk patients who could benefit from intervention. Herein, we focus on current management strategies for ICAS-large vessel occlusion discussed, including the use of perfusion imaging, endovascular therapy, and stenting. In addition, we focus on strategies that aim at identifying subjects at higher risk for early recurrent risk who could benefit from early endovascular intervention The review underscores the need for further research to optimize ICAS-large vessel occlusion treatment strategies, a traditionally understudied topic.

Treatment and Outcomes of Cervical Artery Dissection in Adults: A Scientific Statement From the American Heart Association.

Cervical artery dissection is an important cause of stroke, particularly in young adults. Data conflict on the diagnostic evaluation and treatment of patients with suspected cervical artery dissection, leading to variability in practice. We aim to provide an overview of cervical artery dissection in the setting of minor or no reported mechanical trigger with a focus on summarizing the available evidence and providing suggestions on the diagnostic evaluation, treatment approaches, and outcomes. Writing group members drafted their sections using a literature search focused on publications between January 1, 1990, and December 31, 2022, and included randomized controlled trials, prospective and retrospective observational studies, meta-analyses, opinion papers, case series, and case reports. The writing group chair and vice chair compiled the manuscript and obtained writing group members' approval. Cervical artery dissection occurs as a result of the interplay among risk factors, minor trauma, anatomic and congenital abnormalities, and genetic predisposition. The diagnosis can be challenging both clinically and radiologically. In patients with acute ischemic stroke attributable to cervical artery dissection, acute treatment strategies such as thrombolysis and mechanical thrombectomy are reasonable in otherwise eligible patients. We suggest that the antithrombotic therapy choice be individualized and continued for at least 3 to 6 months. The risk of recurrent dissection is low, and preventive measures may be considered early after the diagnosis and continued in high-risk patients. Ongoing longitudinal and population-based observational studies are needed to close the present gaps on preferred antithrombotic regimens considering clinical and radiographic prognosticators of cervical artery dissection.

Anticoagulation Versus Antiplatelets in Spontaneous Cervical Artery Dissection: A Systematic Review and Meta-Analysis.

BACKGROUND: It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following the publication of the observational Antithrombotic for STOP-CAD (Stroke Prevention in Cervical Artery Dissection) study, which has more than doubled available data, we performed an updated systematic review and meta-analysis comparing antiplatelets versus anticoagulation in cervical artery dissection. METHODS: The systematic review was registered in PROSPERO (CRD42023468063). We searched 5 databases using a combination of keywords that encompass different antiplatelets and anticoagulants, as well as cervical artery dissection. We included relevant randomized trials and included observational studies of dissection unrelated to major trauma. Where studies were sufficiently similar, we performed meta-analyses for efficacy (ischemic stroke) and safety (major hemorrhage, symptomatic intracranial hemorrhage, and death) outcomes using relative risks. RESULTS: We identified 11 studies (2 randomized trials and 9 observational studies) that met the inclusion criteria. These included 5039 patients (30% [1512] treated with anticoagulation and 70% [3527]) treated with antiplatelets]. In meta-analysis, anticoagulation was associated with a lower ischemic stroke risk (relative risk, 0.63 [95% CI, 0.43 to 0.94]; P=0.02; I2=0%) but higher major bleeding risk (relative risk, 2.25 [95% CI, 1.07 to 4.72]; P=0.03, I2=0%). The risks of death and symptomatic intracranial hemorrhage were similar between the 2 treatments. Effect sizes were larger in randomized trials. There are insufficient data on the efficacy and safety of dual antiplatelet therapy or direct oral anticoagulants. CONCLUSIONS: In this study of patients with cervical artery dissection, anticoagulation was superior to antiplatelet therapy in reducing ischemic stroke but carried a higher major bleeding risk. This argues for an individualized therapeutic approach incorporating the net clinical benefit of ischemic stroke reduction and bleeding risks. Large randomized clinical trials are required to clarify optimal antithrombotic strategies for management of cervical artery dissection.

Transcarotid Arterial Revascularization of Symptomatic Internal Carotid Artery Disease: A Systematic Review and Study-Level Meta-Analysis.

BACKGROUND: Transcarotid artery revascularization (TCAR) is an interventional therapy for symptomatic internal carotid artery disease. Currently, the utilization of TCAR is contentious due to limited evidence. In this study, we evaluate the safety and efficacy of TCAR in patients with symptomatic internal carotid artery disease compared with carotid endarterectomy (CEA) and carotid artery stenting (CAS). METHODS: A systematic review was conducted, spanning from January 2000 to February 2023, encompassing studies that used TCAR for the treatment of symptomatic internal carotid artery disease. The primary outcomes included a 30-day stroke or transient ischemic attack, myocardial infarction, and mortality. Secondary outcomes comprised cranial nerve injury and major bleeding. Pooled odds ratios (ORs) for each outcome were calculated to compare TCAR with CEA and CAS. Furthermore, subgroup analyses were performed based on age and degree of stenosis. In addition, a sensitivity analysis was conducted by excluding the vascular quality initiative registry population. RESULTS: A total of 7 studies involving 24 246 patients were analyzed. Within this patient cohort, 4771 individuals underwent TCAR, 12 350 underwent CEA, and 7125 patients underwent CAS. Compared with CAS, TCAR was associated with a similar rate of stroke or transient ischemic attack (OR, 0.77 [95% CI, 0.33-1.82]) and myocardial infarction (OR, 1.29 [95% CI, 0.83-2.01]) but lower mortality (OR, 0.42 [95% CI, 0.22-0.81]). Compared with CEA, TCAR was associated with a higher rate of stroke or transient ischemic attack (OR, 1.26 [95% CI, 1.03-1.54]) but similar rates of myocardial infarction (OR, 0.9 [95% CI, 0.64-1.38]) and mortality (OR, 1.35 [95% CI, 0.87-2.10]). CONCLUSIONS: Although CEA has traditionally been considered superior to stenting for symptomatic carotid stenosis, TCAR may have some advantages over CAS. Prospective randomized trials comparing the 3 modalities are needed.

Endovascular Versus Medical Therapy in Posterior Cerebral Artery Stroke: Role of Baseline NIHSS Score and Occlusion Site.

BACKGROUND: Acute ischemic stroke with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the association between endovascular treatment (EVT) and outcomes in iPCAO acute ischemic stroke is modified by initial stroke severity (baseline National Institutes of Health Stroke Scale [NIHSS]) and arterial occlusion site. METHODS: Based on the multicenter, retrospective, case-control study of consecutive iPCAO acute ischemic stroke patients (PLATO study [Posterior Cerebral Artery Occlusion Stroke]), we assessed the heterogeneity of EVT outcomes compared with medical management (MM) for iPCAO, according to baseline NIHSS score (≤6 versus >6) and occlusion site (P1 versus P2), using multivariable regression modeling with interaction terms. The primary outcome was the favorable shift of 3-month modified Rankin Scale (mRS). Secondary outcomes included excellent outcome (mRS score 0-1), functional independence (mRS score 0-2), symptomatic intracranial hemorrhage, and mortality. RESULTS: From 1344 patients assessed for eligibility, 1059 were included (median age, 74 years; 43.7% women; 41.3% had intravenous thrombolysis): 364 receiving EVT and 695 receiving MM. Baseline stroke severity did not modify the association of EVT with 3-month mRS distribution (Pinteraction=0.312) but did with functional independence (Pinteraction=0.010), with a similar trend on excellent outcome (Pinteraction=0.069). EVT was associated with more favorable outcomes than MM in patients with baseline NIHSS score >6 (mRS score 0-1, 30.6% versus 17.7%; adjusted odds ratio [aOR], 2.01 [95% CI, 1.22-3.31]; mRS score 0 to 2, 46.1% versus 31.9%; aOR, 1.64 [95% CI, 1.08-2.51]) but not in those with NIHSS score ≤6 (mRS score 0-1, 43.8% versus 46.3%; aOR, 0.90 [95% CI, 0.49-1.64]; mRS score 0-2, 65.3% versus 74.3%; aOR, 0.55 [95% CI, 0.30-1.0]). EVT was associated with more symptomatic intracranial hemorrhage regardless of baseline NIHSS score (Pinteraction=0.467), while the mortality increase was more pronounced in patients with NIHSS score ≤6 (Pinteraction=0.044; NIHSS score ≤6: aOR, 7.95 [95% CI, 3.11-20.28]; NIHSS score >6: aOR, 1.98 [95% CI, 1.08-3.65]). Arterial occlusion site did not modify the association of EVT with outcomes compared with MM. CONCLUSIONS: Baseline clinical stroke severity, rather than the occlusion site, may be an important modifier of the association between EVT and outcomes in iPCAO. Only severely affected patients with iPCAO (NIHSS score >6) had more favorable disability outcomes with EVT than MM, despite increased mortality and symptomatic intracranial hemorrhage.

Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P=0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P=0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P=0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P=0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; Pinteraction=0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

Effect of Alteplase on Ischemic Stroke Mortality Is Dependent on Stroke Severity.

OBJECTIVE: Although intravenous alteplase (IV-tPA) has a beneficial effect on functional outcome after ischemic stroke (IS), prior studies of IV-tPA's impact on post-stroke mortality did not have sufficient representation of more severe stroke. METHODS: We determined if the interaction between the baseline National Institutes of Health (NIH) Stroke Scale (NIHSS) and IV-tPA modified the risk of mortality after IS in two cohorts: (1) National Inpatient Sample 2016-2020, and (2) a harmonized cohort of IS patients from the NINDS IV-tPA, ALIAS part 2, SHINE, FAST-MAG, IMS-III, POINT, and DEFUSE 3 trials. We fit logistic regression models to the outcome of in-hospital mortality (National Inpatient Sample [NIS] cohort) or mortality within 90 days (harmonized cohort), adjusted for baseline variables. RESULTS: We included 198,668 patients in the NIS cohort, of which 14.0% received IV-tPA and 3.4% died in hospital. We included 7,138 patients in the harmonized cohort, of which 33.2% received IV-tPA and 9.4% died by 90 days. Mortality in the NIS cohort was associated with older age, female sex, non-Hispanic white race, atrial fibrillation, and higher NIHSS. In the harmonized cohort, mortality was associated with older age, diabetes, atrial fibrillation, and higher NIHSS. In both cohorts, the interaction between NIHSS and IV-tPA was significant. In the NIS cohort, the separation became significant at NIHSS 15 and in the harmonized cohort at NIHSS 23, at which point, IV-tPA began to have a significant benefit for both in-hospital and 90-day mortality, respectively. INTERPRETATION: IV-tPA is associated with a reduction in both in-hospital and 90-day mortality for patients with more severe IS. ANN NEUROL 2023;93:1106-1116.

Perioperative Acute Ischemic Stroke in Patients with Atrial Fibrillation.

OBJECTIVE: Anticoagulation therapy is commonly interrupted in patients with atrial fibrillation (AF) for elective procedures. However, the risk factors of acute ischemic stroke (AIS) during the periprocedural period remain uncertain. We performed a nationwide analysis to evaluate AIS risk factors in patients with AF undergoing elective surgical procedures. METHODS: Using the Nationwide Readmission Database, we included electively admitted adult patients with AF and procedural Diagnosis-Related Group codes from 2016 to 2019. Diagnoses were identified based on International Classification of Disease, 9th revision-Clinical Modification (ICD-10 CM) codes. We constructed a logistic regression model to identify risk factors and developed a new scoring system incorporating CHA2 DS2 VASc to estimate periprocedural AIS risk. RESULTS: Of the 1,045,293 patients with AF admitted for an elective procedure, the mean age was 71.5 years, 39.2% were women, and 0.70% had a perioperative AIS during the index admission or within 30 days of discharge. Active cancer (adjusted OR [aOR] = 1.58, 95% confidence interval [CI] = 1.42-1.76), renal failure (aOR = 1.14, 95% CI = 1.04-1.24), neurological surgery (aOR = 4.51, 95% CI = 3.84-5.30), cardiovascular surgery (aOR = 2.74, 95% CI = 2.52-2.97), and higher CHA2 DS2 VASc scores (aOR 1.25 per point, 95% CI 1.22-1.29) were significant risk factors for periprocedural AIS. The new scoring system (area under the receiver operating characteristic curve [AUC] = 0.68, 95% CI = 0.67 to 0.79) incorporating surgical type and cancer outperformed CHA2 DS2 VASc (AUC = 0.60, 95% CI = 0.60 to 0.61). INTERPRETATION: In patients with AF, periprocedural AIS risk increases with the CHA2 DS2 VASc score, active cancer, and cardiovascular or neurological surgeries. Studies are needed to devise better strategies to mitigate perioperative AIS risk in these patients. ANN NEUROL 2023;94:321-329.

Real-World Outcomes of Endovascular Thrombectomy for Basilar Artery Occlusion: Results of the BArONIS Study.

OBJECTIVE: To evaluate clinical outcomes of endovascular thrombectomy (EVT) for acute basilar artery occlusion (BAO) using population-level data from the United States. METHODS: Weighted discharge data from the National Inpatient Sample were queried to identify adult patients with acute BAO during the period of 2015 to 2019 treated with EVT or medical management only. Complex samples statistical methods and propensity-score adjustment using inverse probability of treatment weighting (IPTW) were performed to assess clinical endpoints. RESULTS: Among 3,950 BAO patients identified, 1,425 (36.1%) were treated with EVT [mean age 66.7 years, median National Institute of Health Stroke Scale (NIHSS) score 22]. On unadjusted analysis, 155 (10.9%) EVT patients achieved favorable functional outcomes (discharge disposition to home without services), while 515 (36.1%) experienced in-hospital mortality, and 20 (1.4%) developed symptomatic intracranial hemorrhage (sICH). Following propensity-score adjustment by IPTW accounting for age, stroke severity, and comorbidity burden, EVT was independently associated with favorable functional outcome [adjusted odds ratio (aOR) 1.25, 95% confidence interval (CI) 1.07, 1.46; p = 0.004], but not with in-hospital mortality or sICH. In an IPTW-adjusted sub-group analysis of patients with NIHSS scores >20, EVT was associated with both favorable functional outcome (discharge disposition to home or to acute rehabilitation) (aOR 1.55, 95% CI 1.24, 1.94; p < 0.001) and decreased mortality (aOR 0.78, 95% CI 0.69, 0.89; p < 0.001), but not with sICH. INTERPRETATION: This retrospective population-based analysis using a large national registry provides real-world evidence of a potential benefit of EVT in acute BAO patients. ANN NEUROL 2023;94:55-60.

Advances in Recurrent Stroke Prevention: Focus on Antithrombotic Therapies.

The past decade has seen significant advances in stroke prevention. These advances include new antithrombotic agents, new options for dyslipidemia treatment, and novel techniques for surgical stroke prevention. In addition, there is greater recognition of the benefits of multifaceted interventions, including the role of physical activity and dietary modification. Despite these advances, the aging of the population and the high prevalence of key vascular risk factors pose challenges to reducing the burden of stroke. Using a cause-based framework, current approaches to prevention of cardioembolic, cryptogenic, atherosclerotic, and small vessel disease stroke are outlined in this paper. Special emphasis is given to recent trials of antithrombotic agents, including studies that have tested combination treatments and responses according to genetic factors.

Endovascular therapy for cerebral venous thrombosis: Applying lessons learned from clinical trials of EVT in acute arterial ischemic stroke.

Cerebral venous thrombosis (CVT) is a rare but severely disabling form of stroke. Acute treatment mainly consists of medical management, since there is no robust evidence suggesting benefit of endovascular treatment for CVT. Given the relative lack of data to guide acute treatment decision-making, CVT treatment decisions are mostly made on a case-by-case basis. In some ways, the current status quo of endovascular treatment for cerebral venous thrombosis (CVT) resembles the state of endovascular treatment for acute ischemic stroke before the wave of major positive large vessel occlusion endovascular treatment trials in 2015. In this review, we summarize the current state of evidence with regard to endovascular CVT treatment, draw parallels to acute ischemic stroke, and discuss how the lessons learned from the evolution of acute ischemic stroke EVT trials could be applied to designing a trial of endovascular treatment for CVT. We end by outlining possible scenarios for the future of endovascular CVT treatment.

FLAIR signal intensity ratio predicts small subcortical infarct early neurologic deterioration: a cross-sectional study.

PURPOSE: Prior studies have used the fluid-attenuated inversion recovery sequence signal intensity ratio (FLAIR-SIR) to predict those with an incomplete infarct that may safely receive acute thrombolytics. Clinical early neurologic deterioration (END) of small subcortical infarcts (SSIs) is suspected to occur due to delayed infarct completion. We aimed to understand if a lower FLAIR-SIR, suggestive of an incomplete infarct, would have a higher likelihood of SSI-related END. METHODS: A cross-sectional retrospective study was performed of those with an acute SSI (anterior or posterior circulation) without significant parent vessel steno-occlusive disease. END was defined as a new or worsened disabling neurologic deficit during the index hospitalization. Standard-of-care brain MRIs were reviewed from the hospitalization, and a FLAIR-SIR cutoff of ≤ 1.15 was used based on prior studies. Adjusted logistic regression models were used for analysis. RESULTS: We identified 252 patients meeting inclusion criteria: median (IQR) age 68 (12) years, 38.5% (97/252) female, and 11% (28/252) with END. Tobacco use was more common in those without END (32%) compared with END (55%, p = 0.03). In adjusted analyses, a FLAIR-SIR cutoff of ≤ 1.15 yielded an odds ratio of 2.8 (95% CI 1.23-6.13, p = 0.012) of early neurological deterioration. CONCLUSION: Those with a FLAIR-SIR ≤ 1.15 are nearly threefold more likely to develop SSI-related END.

Cerebral venous sinus thrombosis associated with cancer: analysis of the ACTION-CVT study.

Nearly one fifth of patients with venous thromboembolism (VTE) have cancer. When both of these conditions occur, especially in cases of cerebral vein thrombosis (CVT), patient management is often challenging. The aim of this study was to compare the characteristics and event courses in patients affected by CVT with and without cancer. Consecutive patients with CVT from the ACTION-CVT cohort study were included if cancer status was reported. Risk factors as well as the clinical and radiological characteristics of patients were compared. Univariable and multivariable analyses were performed to assess variables associated with cancer. Kaplan-Meier method and log-rank test, logistic regression analysis, and propensity score matching were used to investigate any association between cancer-related CVT and study outcomes (primary outcome at 3-months: recurrent VTE or major hemorrhage; recurrent VTE; major hemorrhage; recanalization status; all-cause-death). Overall, 1,023 patients with CVT were included, of which 6.5% had cancer. Older age (adjusted odds ratio [aOR] 1.28 per decade increase; 95% confidence interval [CI] 1.08-1.52) and absence of headache (aOR 0.47; 95% CI 0.27-0.84) were independently associated with cancer. Patients with cancer had a higher risk of recurrent VTE or major hemorrhage (aOR 3.87; 95% CI 2.09-7.16), all-cause-death (aOR 7.56 95% CI 3.24-17.64), and major hemorrhage (aOR 3.70 95% CI 1.76-7.80). Recanalization rates, partial or complete, was not significantly different. CVT patients with cancer were more likely to be older, have no referred headache, and have worse outcomes compared to CVT patients without cancer.

Left atrial strain, embolic stroke of undetermined source, and atrial fibrillation detection.

BACKGROUND: Atrial cardiopathy is a proposed mechanism of embolic stroke of undetermined source (ESUS). Left atrial (LA) strain may identify early atrial cardiopathy prior to structural changes. We aim to study the associations between LA strain, ESUS, and atrial fibrillation (AF) detection in ESUS. METHODS: The study population included patients with ESUS and noncardioembolic (NCE) stroke presenting to the Rhode Island Hospital Stroke Center between January 2016 and June 2017 who underwent transthoracic echocardiography. Speckle tracking echocardiography (STE) was used to measure the three phases of LA strain (reservoir, conduit, and contractile). Binary logistic regression analysis was performed to determine the associations between LA strain and stroke subtype (ESUS vs. NCE) as well as follow-up detection of AF in ESUS patients. RESULTS: We identified 656 patients, 307 with ESUS and 349 with NCE. In binary logistic regression, the lowest tertiles of LA reservoir (adjusted OR 1.944, 95% CI 1.266-2.986, p = .002), contractile (aOR 1.568, 95% CI 1.035-2.374, p = .034), and conduit strain (aOR 2.288, 95% CI 1.448-3.613, p = .001) were more likely to be significantly associated with ESUS compared to NCE stroke. Among all ESUS patients, the lowest tertiles of LA reservoir strain (OR 2.534, 95% CI 1.029-6.236, p = .043), contractile strain (OR 2.828, 95% CI 1.158-6.903, p = .022), and conduit strain (OR 2.614, 95% CI 1.003-6.815, p = .049) were significantly associated with subsequent detection of AF. CONCLUSION: Reduced LA strain is associated with ESUS occurrence and AF detection in ESUS patients. Therefore, quantification of LA strain in ESUS patients may improve risk stratification and guide secondary prevention strategies.

The impact of pre-stroke aspirin exposure on radiographic appearance and disability outcomes: A post-hoc analysis of the SPS3 trial: Aspirin Use and Small Subcortical Stroke.

OBJECTIVES: The effect of pre-stroke use of aspirin on small subcortical infarct dimensions or outcomes is not well described. We aimed to bridge this knowledge gap amongst a well-described and heterogeneous patient population. MATERIALS AND METHODS: We performed a post-hoc analysis of the Secondary Prevention of Small Subcortical Stroke (SPS3) trial. The primary exposure was aspirin use ≤7 days of index stroke. The primary outcomes were infarct dimensions. Functional outcomes by modified Rankin Scale (mRS) was a secondary outcome. Age restricted (≥55 years) subgroup analyses were performed as a sensitivity analysis. Descriptive statistical and regression modeling were performed for data analysis. RESULTS: We included 1423 participants of which 453(31.8 %) used aspirin. Aspirin use was associated with more cardiovascular risk diagnoses. Maximal infarct diameter did not differ with pre-stroke aspirin use (11.3±4.2 mm versus 11.8±4.1 mm, p=0.057) however infarct area was smaller with exposure (126.4±90.0 mm2 versus 137.4±97.0 mm2, p=0.037) regardless of aspirin strength. Participants ≥55 years had smaller infarct diameters (11.1±4.2 mm versus 11.9±4.4 mm, p=0.019) and area (123.4±87.1 mm2 versus 130.6±93.2 mm2, p=0.037) with aspirin use. mRS did not significantly differ in our analyses. CONCLUSIONS: In this post-hoc analysis of the SPS3 trial, pre-stroke aspirin use was associated with a smaller infarct area regardless of aspirin strength and without impact on functional outcomes. These findings were more pronounced in participants ≥55 years. REGISTRATION: https://clinicaltrials.gov/study/NCT00059306?term= %22sps3 %22&rank=1.

Higher blood glucose is associated with the severity of hemorrhagic transformation after endovascular therapy for stroke.

OBJECTIVES: Hyperglycemia is associated with poor outcome in large vessel occlusion (LVO) stroke, with mechanism for this effect unknown. MATERIALS AND METHODS: We used our prospective, multicenter, observational study, Blood Pressure After Endovascular Stroke Therapy (BEST), of anterior circulation LVO stroke undergoing endovascular therapy (EVT) from 11/2017-7/2018 to determine association between increasing blood glucose (BG) and intracerebral hemorrhage (ICH). Our primary outcome was degree of ICH, classified as none, asymptomatic ICH, or symptomatic ICH (≥4-point increase in National Institutes of Health Stroke Scale [NIHSS] at 24 h with any hemorrhage on imaging). Secondary outcomes included 24 h NIHSS, early neurologic recovery (ENR, NIHSS 0-1 or NIHSS reduction by ≥8 within 24 h), and 90-day modified Rankin Scale (mRS) using univariate and multivariable regression. RESULTS: Of 485 enrolled patients, increasing BG was associated with increasing severity of ICH (adjusted OR, aOR 1.06, 95 % CI 1.02-1.1, p < 0.001), higher 24 h NIHSS (aOR 1.22, 95 % CI 1.11-1.34, p < 0.001), ENR (aOR 0.90, 95 % CI 0.82-1.00, p < 0.002), and 90-day mRS (aOR 1.06, 95 % CI 1.03-1.09, p < 0.001) when adjusted for age, presenting NIHSS, ASPECTS, 24-hour peak systolic blood pressure, time from last known well, and successful recanalization. CONCLUSIONS: In the BEST study, increasing BG was associated with greater odds of increasing ICH severity. Further study is warranted to determine whether treatment of will decrease ICH severity following EVT.

IV Thrombolysis for central retinal artery occlusion - Real-world experience from a comprehensive stroke center.

OBJECTIVES: Central retinal artery occlusion (CRAO) is a stroke of the retina potentially amenable to intravenous thrombolysis (IVT). We aimed to determine feasibility of an emergency treatment protocol and risk profile of IVT for CRAO in a comprehensive stroke center (CSC). METHODS: We performed a retrospective, observational cohort study including patients with acute CRAO admitted to a CSC over 4 years. Patients are offered IVT if they present with acute vision loss of ≤ 20/200 in the affected eye, have no other cause of vision loss (incorporating a dilated ophthalmologic exam), and meet criteria akin to acute ischemic stroke. We collected socio-demographic data, triage data, time from onset to presentation, IVT candidacy, and rates of symptomatic intracranial hemorrhage (sICH)- or extracranial hemorrhage. RESULTS: 36 patients presented within the study period, mean (standard deviation (SD)) age of 70.7 (10), 52 % female, and median time (Q1, Q3) to ED presentation of 13.5 (4.3, 18.8) h. Patients within 4.5 h from onset presented more commonly directly to our ED (66.6 % vs 37.1 %, p = 0.1). Nine patients (25 %) presented within the 4.5 h window. Of those eligible, 7 (77 %) received IVT. There were no events of intracranial or extracranial hemorrhage. CONCLUSIONS: Our study confirmed that IVT for acute CRAO is feasible. We found a high rate of treatment with IVT of those eligible. However, because 75 % of patients presented outside the treatment window, continued educational efforts are needed to improve rapid triage to emergency departments to facilitate evaluation for possible candidacy with IVT.

Trends in cerebral venous thrombosis before and during the COVID-19 pandemic: Analysis of the National Inpatient Sample.

OBJECTIVES: We sought to provide updated incidence and trend data for cerebral venous thrombosis (CVT) in the United States from 2016-2020, examine the impact of the COVID-19 pandemic on CVT, and identify predictors of in-hospital mortality. MATERIALS AND METHODS: Validated ICD-10 codes were used to identify discharges with CVT in the National Inpatient Sample (NIS). Sample weights were applied to generate nationally representative estimates, and census data were used to compute incidence rates. The first wave of the COVID-19 pandemic was defined as January-May 2020. Trend analysis was completed using Joinpoint regression. RESULTS: From 2016 to 2020, the incidence of CVT increased from 24.34 per 1,000,000 population per year (MPY) to 33.63 per MPY (Annual Percentage Change (APC) 8.6 %; p < 0.001). All-cause in-hospital mortality was 4.9 % [95 % CI 4.5-5.4]. On multivariable analysis, use of thrombectomy, increased age, atrial fibrillation, stroke diagnosis, infection, presence of prothrombotic hematologic conditions, lowest quartile of income, intracranial hemorrhage, and male sex were associated with in-hospital mortality. CVT incidence was similar comparing the first 5 months of 2020 and 2019 (31.37 vs 32.04; p = 0.322) with no difference in median NIHSS (2 [IQR 1-10] vs. 2 [1-9]; p = 0.959) or mortality (4.2 % vs. 5.6 %; p = 0.176). CONCLUSIONS: CVT incidence increased in the US from 2016 to 2020 while mortality did not change. Increased age, prothrombotic state, stroke diagnosis, infection, atrial fibrillation, male sex, lowest quartile of income, intracranial hemorrhage, and use of thrombectomy were associated with in-hospital mortality following CVT. During the first wave of the COVID-19 pandemic, CVT volumes and mortality were similar to the prior year.

External validation of the SI2NCAL2C score for outcomes following cerebral venous thrombosis.

OBJECTIVES: Prognostication for cerebral venous thrombosis (CVT) remains difficult. We sought to validate the SI2NCAL2C score in an international cohort. MATERIALS AND METHODS: The SI2NCAL2C score was originally developed to predict poor outcome (modified Rankin Scale (mRS) 3-6) at 6 months, and mortality at 30 days and 1 year using data from the International CVT Consortium. The SI2NCAL2C score uses 9 variables: the absence of any female-sex-specific risk factors, intracerebral hemorrhage, central nervous system infection, focal neurological deficits, coma, age, lower level of hemoglobin, higher level of glucose, and cancer. The ACTION-CVT study was an international retrospective study that enrolled consecutive patients across 27 centers. The poor outcome score was validated using 90-day mRS due to lack of follow-up at the 6-month time-point in the ACTION-CVT cohort. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Missing data were imputed using the additive regression and predictive mean matching methods. Bootstrapping was performed with 1000 iterations. RESULTS: Mortality data were available for 950 patients and poor outcome data were available for 587 of 1,025 patients enrolled in ACTION-CVT. Compared to the International CVT Consortium, the ACTION-CVT cohort was older, less often female, and with milder clinical presentation. Mortality was 2.5% by 30 days and 6.0% by one year. At 90-days, 16.7% had a poor outcome. The SI2NCAL2C score had an AUC of 0.74 [95% CI 0.69-0.79] for 90-day poor outcome, 0.72 [0.60-0.82] for mortality by 30 days, and 0.82 [0.76-0.88] for mortality by one year. CONCLUSIONS: The SI2NCAL2C score had acceptable to good performance in an international external validation cohort. The SI2NCAL2C score warrants additional validation studies in diverse populations and clinical implementation studies.