Cerebrospinal Fluid Biomarkers for Diagnosis and the Prognostication of Acute Ischemic Stroke: A Systematic Review.

Despite the high incidence and burden of stroke, biological biomarkers are not used routinely in clinical practice to diagnose, determine progression, or prognosticate outcomes of acute ischemic stroke (AIS). Because of its direct interface with neural tissue, cerebrospinal fluid (CSF) is a potentially valuable source for biomarker development. This systematic review was conducted using three databases. All trials investigating clinical and preclinical models for CSF biomarkers for AIS diagnosis, prognostication, and severity grading were included, yielding 22 human trials and five animal studies for analysis. In total, 21 biomarkers and other multiomic proteomic markers were identified. S100B, inflammatory markers (including tumor necrosis factor-alpha and interleukin 6), and free fatty acids were the most frequently studied biomarkers. The review showed that CSF is an effective medium for biomarker acquisition for AIS. Although CSF is not routinely clinically obtained, a potential benefit of CSF studies is identifying valuable biomarkers from the pathophysiologic microenvironment that ultimately inform optimization of targeted low-abundance assays from peripheral biofluid samples (e.g., plasma). Several important catabolic and anabolic markers can serve as effective measures of diagnosis, etiology identification, prognostication, and severity grading. Trials with large cohorts studying the efficacy of biomarkers in altering clinical management are still needed.

Global, Regional, and National Economic Consequences of Stroke.

BACKGROUND: An understanding of global, regional, and national macroeconomic losses caused by stroke is important for allocation of clinical and research resources. The authors investigated the macroeconomic consequences of stroke disease burden in the year 2019 in 173 countries. METHODS: Disability-adjusted life year data for overall stroke and its subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) were collected from the GBD study (Global Burden of Disease) 2019 database. Gross domestic product (GDP, adjusted for purchasing power parity [PPP]) data were collected from the World Bank; GDP and disability-adjusted life year data were combined to estimate macroeconomic losses using a value of lost welfare (VLW) approach. All results are presented in 2017 international US dollars adjusted for PPP. RESULTS: Globally, in 2019, VLW due to stroke was $2059.67 billion or 1.66% of the global GDP. Global VLW/GDP for stroke subtypes was 0.78% (VLW=$964.51 billion) for ischemic stroke, 0.71% (VLW=$882.81 billion) for intracerebral hemorrhage, and 0.17% (VLW=$212.36 billion) for subarachnoid hemorrhage. The Central European, Eastern European, and Central Asian GBD super-region reported the highest VLW/GDP for stroke overall (3.01%), ischemic stroke (1.86%), and for subarachnoid hemorrhage (0.26%). The Southeast Asian, East Asian, and Oceanian GBD super-region reported the highest VLW/GDP for intracerebral hemorrhage (1.48%). CONCLUSIONS: The global macroeconomic consequences related to stroke are vast even when considering stroke subtypes. The present quantification may be leveraged to help justify increased spending of finite resources on stroke in an effort to improve outcomes for patients with stroke globally.

Endovascular Versus Medical Management of Posterior Cerebral Artery Occlusion Stroke: The PLATO Study.

BACKGROUND: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion. METHODS: This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift and ≥2-point decrease in the National Institutes of Health Stroke Scale. RESULTS: Of 1023 patients, 589 (57.6%) were male with median (interquartile range) age of 74 (64-82) years. The median (interquartile range) National Institutes of Health Stroke Scale was 6 (3-10). The occlusion segments were P1 (41.2%), P2 (49.2%), and P3 (7.1%). Overall, intravenous thrombolysis was administered in 43% and EVT in 37%. There was no difference between the EVT and MM groups in the 90-day modified Rankin Scale shift (aOR, 1.13 [95% CI, 0.85-1.50]; P=0.41). There were higher odds of a decrease in the National Institutes of Health Stroke Scale by ≥2 points with EVT (aOR, 1.84 [95% CI, 1.35-2.52]; P=0.0001). Compared with MM, EVT was associated with a higher likelihood of excellent outcome (aOR, 1.50 [95% CI, 1.07-2.09]; P=0.018), complete vision recovery, and similar rates of functional independence (modified Rankin Scale score, 0-2), despite a higher rate of SICH and mortality (symptomatic intracranial hemorrhage, 6.2% versus 1.7%; P=0.0001; mortality, 10.1% versus 5.0%; P=0.002). CONCLUSIONS: In patients with isolated posterior cerebral artery occlusion, EVT was associated with similar odds of disability by ordinal modified Rankin Scale, higher odds of early National Institutes of Health stroke scale improvement, and complete vision recovery compared with MM. There was a higher likelihood of excellent outcome in the EVT group despite a higher rate of symptomatic intracranial hemorrhage and mortality. Continued enrollment into ongoing distal vessel occlusion randomized trials is warranted.

Direct Transfer to the Neuroangiography Suite for Patients With Stroke.

The therapeutic focus in acute ischemic stroke over the last 2.5 decades has been to balance the benefits of rapid reperfusion therapy with the risks of treatment-related complications. Both intravenous thrombolytics and endovascular thrombectomy are proven to substantially improve outcomes in a time-dependent manner. Each minute saved in achieving successful reperfusion grants an additional week of healthy life and may salvage up to 27 million neurons. The current approach to patient triage is inherited from the preendovascular thrombectomy era of stroke care. Current workflow concentrates on stabilization, diagnosis, and decision-making in the emergency department, followed by thrombolysis if eligible and subsequent transfer to the angiography suite as needed for further treatment. Multiple efforts have been directed toward minimizing the time from first medical contact to reperfusion therapy including prehospital triage and intrahospital workflow. Novel approaches for stroke patient triage such as the direct to angio approach, (also referred to as One Stop Management) are currently in development. The concept was initially introduced as several single-center experiences. In this narrative review article, we will consider various definitions of direct to angio and its variants, discuss its rationale, review its safety and efficacy, assess its feasibility, and delineate its limitations. Further, we will address methods to overcome these limitations and the potential impact of emerging data and new technologies on the direct-to-angio approach.

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.

Mechanical Thrombectomy Global Access For Stroke (MT-GLASS): A Mission Thrombectomy (MT-2020 Plus) Study.

BACKGROUND: Despite the well-established potent benefit of mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke, access to MT has not been studied globally. We conducted a worldwide survey of countries on 6 continents to define MT access (MTA), the disparities in MTA, and its determinants on a global scale. METHODS: Our survey was conducted in 75 countries through the Mission Thrombectomy 2020+ global network between November 22, 2020, and February 28, 2021. The primary end points were the current annual MTA, MT operator availability, and MT center availability. MTA was defined as the estimated proportion of patients with LVO receiving MT in a given region annually. The availability metrics were defined as ([current MT operators×50/current annual number of estimated thrombectomy-eligible LVOs]×100 = MT operator availability) and ([current MT centers×150/current annual number of estimated thrombectomy-eligible LVOs]×100= MT center availability). The metrics used optimal MT volume per operator as 50 and an optimal MT volume per center as 150. Multivariable-adjusted generalized linear models were used to evaluate factors associated with MTA. RESULTS: We received 887 responses from 67 countries. The median global MTA was 2.79% (interquartile range, 0.70-11.74). MTA was <1.0% for 18 (27%) countries and 0 for 7 (10%) countries. There was a 460-fold disparity between the highest and lowest nonzero MTA regions and low-income countries had 88% lower MTA compared with high-income countries. The global MT operator availability was 16.5% of optimal and the MT center availability was 20.8% of optimal. On multivariable regression, country income level (low or lower-middle versus high: odds ratio, 0.08 [95% CI, 0.04-0.12]), MT operator availability (odds ratio, 3.35 [95% CI, 2.07-5.42]), MT center availability (odds ratio, 2.86 [95% CI, 1.84-4.48]), and presence of prehospital acute stroke bypass protocol (odds ratio, 4.00 [95% CI, 1.70-9.42]) were significantly associated with increased odds of MTA. CONCLUSIONS: Access to MT on a global level is extremely low, with enormous disparities between countries by income level. The significant determinants of MT access are the country's per capita gross national income, prehospital LVO triage policy, and MT operator and center availability.

Factors associated with readmission after minimally invasive transforaminal lumbar interbody fusion.

OBJECTIVE: The objective of this study was to identify factors that lead to a prolonged hospital stay or 30-day readmission after minimally invasive surgery (MIS) for transforaminal lumbar interbody fusion (TLIF) at a single institution. METHODS: Consecutive patients who underwent MIS TLIF from January 1, 2016, to March 31, 2018, were retrospectively analyzed. Demographic data, including age, sex, ethnicity, smoking status, and body mass index, were collected along with operative details, indications, affected spinal levels, estimated blood loss, and operative duration. The effects of these data were evaluated relative to the hospital length of stay (LOS) and 30-day readmission. RESULTS: The authors identified 174 consecutive patients who underwent MIS TLIF at 1 or 2 levels from a prospectively collected database. The mean (range) patient age was 64.1 (31-81) years, 97 were women (56%), and 77 were men (44%). Of 182 levels fused, 127 were done at L4-5 (70%), 32 at L3-4 (18%), 13 at L5-S1 (7%), and 10 at L2-3 (5%). Patients underwent 166 (95%) single-level procedures and 8 (5%) 2-level procedures. The mean (range) procedural duration, defined as the time from incision to closure, was 164.6 (90-529) minutes. The mean (range) LOS was 1.8 (0-8) days. Eleven patients (6%) were readmitted within 30 days; the most frequent causes were urinary retention, constipation, and persistent or contralateral symptoms. Seventeen patients had LOS greater than 3 days. Six of those patients (35%) were identified as widows, widowers, or divorced, and 5 of them lived alone. Six patients with prolonged LOS (35%) required placement in either skilled nursing or acute inpatient rehabilitation. Regression analyses showed living alone (p = 0.04) and diabetes (p = 0.04) as predictors of readmission. Regression analyses revealed female sex (p = 0.03), diabetes (p = 0.03), and multilevel surgery (p = 0.006) as predictors of LOS > 3 days. CONCLUSIONS: Urinary retention, constipation, and persistent radicular symptoms were the leading causes of readmission within 30 days of surgery in this series, which is distinct from data from the American College of Surgeons National Surgical Quality Improvement Program. The inability to discharge a patient home for social reasons led to prolonged inpatient hospital stays. Identifying these risk factors and proactively addressing them could lower readmission rates and decrease LOS among patients undergoing MIS TLIF.

Precision Effects of Glibenclamide on MRI Endophenotypes in Clinically Relevant Murine Traumatic Brain Injury.

OBJECTIVES: Addressing traumatic brain injury (TBI) heterogeneity is increasingly recognized as essential for therapy translation given the long history of failed clinical trials. We evaluated differential effects of a promising treatment (glibenclamide) based on dose, TBI type (patient selection), and imaging endophenotype (outcome selection). Our goal to inform TBI precision medicine is contextually timely given ongoing phase 2/planned phase 3 trials of glibenclamide in brain contusion. DESIGN: Blinded randomized controlled preclinical trial of glibenclamide on MRI endophenotypes in two established severe TBI models: controlled cortical impact (CCI, isolated brain contusion) and CCI+hemorrhagic shock (HS, clinically common second insult). SETTING: Preclinical laboratory. SUBJECTS: Adult male C57BL/6J mice (n = 54). INTERVENTIONS: Mice were randomized to naïve, CCI±HS with vehicle/low-dose (20 µg/kg)/high-dose glibenclamide (10 µg/mouse). Seven-day subcutaneous infusions (0.4 µg/hr) were continued. MEASUREMENTS AND MAIN RESULTS: Serial MRI (3 hr, 6 hr, 24 hr, and 7 d) measured hematoma and edema volumes, T2 relaxation (vasogenic edema), apparent diffusion coefficient (ADC, cellular/cytotoxic edema), and 7-day T1-post gadolinium values (blood-brain-barrier [BBB] integrity). Linear mixed models assessed temporal changes. Marked heterogeneity was observed between CCI versus CCI+HS in terms of different MRI edema endophenotypes generated (all p < 0.05). Glibenclamide had variable impact. High-dose glibenclamide reduced hematoma volume ~60% after CCI (p = 0.0001) and ~48% after CCI+HS (p = 4.1 × 10-6) versus vehicle. Antiedema benefits were primarily in CCI: high-dose glibenclamide normalized several MRI endophenotypes in ipsilateral cortex (all p < 0.05, hematoma volume, T2, ADC, and T1-post contrast). Acute effects (3 hr) were specific to hematoma (p = 0.001) and cytotoxic edema reduction (p = 0.0045). High-dose glibenclamide reduced hematoma volume after TBI with concomitant HS, but antiedema effects were not robust. Low-dose glibenclamide was not beneficial. CONCLUSIONS: High-dose glibenclamide benefitted hematoma volume, vasogenic edema, cytotoxic edema, and BBB integrity after isolated brain contusion. Hematoma and cytotoxic edema effects were acute; longer treatment windows may be possible for vasogenic edema. Our findings provide new insights to inform interpretation of ongoing trials as well as precision design (dose, sample size estimation, patient selection, outcome selection, and Bayesian analysis) of future TBI trials of glibenclamide.

Utility of tPA Administration in Acute Treatment of Internal Carotid Artery Occlusions.

Background: Intravenous tissue plasminogen activator (IV-tPA) remains part of the guidelines for acute ischemic stroke treatment, yet internal carotid artery occlusions (ICAO) are known to be poorly responsive to IV-tPA. It is unknown whether bridging thrombolysis (BT) is beneficial in such cases. Purpose: We sought to evaluate whether the use of IV-tPA improved overall clinical outcomes in patients undergoing endovascular thrombectomy (EVT) for ICA occlusions. Methods: Data from 1367 consecutive stroke cases treated with EVT from 2012-2019 were prospectively collected from a single center. Univariate and multivariate logistic regression were used to assess the relationship between IV-tPA administration and clinical outcome. Results: 153 patients were found to have carotid terminus and tandem ICAO who received EVT and presented within 4.5h of last seen well. 50% (n = 82) received IV tPA. There were no differences between the groups with respect to age, NIHSS, time to EVT and ASPECTS score. 53% had tandem ICA-MCA occlusions. Rate of recanalization (≥ TICI 2B) and sICH did not significantly differ between the two groups. Regression analysis demonstrated no effect of IV-tPA on modified Rankin Score (mRS) at 90 days and overall mortality. Factors significantly associated with reduced mortality included lower age, lower NIHSS, and better rate of recanalization. Conclusions: There was no significant difference in clinical outcomes in those receiving BT vs. direct EVT for ICAO. For centers with optimal door-to-puncture times, bypassing IV-tPA may expedite recanalization times and potentially yield more favorable outcomes. Patients with higher NIHSS and tandem lesions may have better outcomes with BT.

Delayed Functional Independence After Neurothrombectomy (DEFIANT) score: analysis of the Trevo Retriever Registry.

BACKGROUND: Chronological heterogeneity in neurological improvement after endovascular thrombectomy (EVT) for large vessel occlusion (LVO) stroke is commonly observed in clinical practice. Understanding the temporal progression of functional independence after EVT, especially delayed functional independence in patients who do not improve early, is essential for prognostication and rehabilitation. We aim to determine the incidence of early functional independence (EFI) and delayed functional independence (DFI), identify associated predictors after EVT, and develop the Delayed Functional Independence After Neurothrombectomy (DEFIANT) score. METHODS: Demographic, clinical, radiological, treatment, and procedural information were analyzed from the Trevo Registry (patients undergoing EVT due to anterior LVO using the Trevo stent retriever). Incidence and predictors of EFI (modified Rankin Scale (mRS) score 0-2 at discharge) and DFI (mRS score 0-2 at 90 days in non-EFI patients) were analyzed. RESULTS: A total of 1623 patients met study criteria. EFI was observed in 45% (730) of patients. Among surviving non-EFI patients (884), DFI was observed in 35% (308). Younger age (p=0.003), lower discharge National Institutes of Health Stroke Scale (NIHSS) score (p<0.0001), and absence of any hemorrhage (p=0.021) were independent predictors of DFI. After age 60, the probability of DFI declines significantly with 5 year age increments (approximately 7% decline for every 5 years; p(DFI)= 1.3559-0.0699, p for slope=0.001). The DEFIANT score is available online (https://bit.ly/3KZRVq5). CONCLUSION: Approximately 45% of patients experience EFI. About one-third of non-early improvers experience DFI. Younger age, lower discharge NIHSS score, and absence of any hemorrhage were independent predictors of DFI among non-early improvers.

Endovascular Therapy vs Medical Management for Patients With Acute Stroke With Medium Vessel Occlusion in the Anterior Circulation.

Importance: Randomized clinical trials have shown the efficacy of endovascular therapy (EVT) for acute large vessel occlusion strokes. The benefit of EVT in acute stroke with distal, medium vessel occlusion (DMVO) remains unclear. Objective: To examine the efficacy and safety outcomes associated with EVT in patients with primary DMVO stroke when compared with a control cohort treated with medical management (MM) alone. Design, Setting, and Participants: This multicenter, retrospective cohort study pooled data from patients who had an acute stroke and a primary anterior circulation emergency DMVO, defined as any segment of the anterior cerebral artery (ACA) or distal middle cerebral artery, between January 1, 2015, and December 31, 2019. Those with a concomitant proximal occlusion were excluded. Outcomes were compared between the 2 treatment groups using propensity score methods. Data analysis was performed from March to June 2021. Exposures: Patients were divided into EVT and MM groups. Main Outcomes and Measures: Main efficacy outcomes included 3-month functional independence (modified Rankin Scale [mRS] scores, 0-2) and 3-month excellent outcome (mRS scores, 0-1). Safety outcomes included 3-month mortality and symptomatic intracranial hemorrhage. Results: A total of 286 patients with DMVO were evaluated, including 156 treated with EVT (mean [SD] age, 66.7 [13.7] years; 90 men [57.6%]; median National Institute of Health Stroke Scale [NIHSS] score, 13.5 [IQR, 8.5-18.5]; intravenous tissue plasminogen activator [IV tPA] use, 75 [49.7%]; ACA involvement, 49 [31.4%]) and 130 treated with medical management (mean [SD] age, 69.8 [14.9] years; 62 men [47.7%]; median NIHSS score, 7.0 [IQR, 4.0-14.0], IV tPA use, 58 [44.6%]; ACA involvement, 31 [24.0%]). There was no difference in the unadjusted rate of 3-month functional independence in the EVT vs MM groups (151 [51.7%] vs 124 [50.0%]; P = .78), excellent outcome (151 [38.4%] vs 123 [31.7%]; P = .25), or mortality (139 [18.7%] vs 106 [11.3%]; P = .15). The rate of symptomatic intracranial hemorrhage was similar in the EVT vs MM groups (weighted: 4.0% vs 3.1%; P = .90). In inverse probability of treatment weighting propensity analyses, there was no significant difference between groups for functional independence (adjusted odds ratio [aOR], 1.36; 95% CI, 0.84-2.19; P = .20) or mortality (aOR, 1.24; 95% CI, 0.63-2.43; P = .53), whereas the EVT group had higher odds of an excellent outcome (mRS scores, 0-1) at 3 months (aOR, 1.71; 95% CI, 1.02-2.87; P = .04). Conclusions and Relevance: The findings of this multicenter cohort study suggest that EVT may be considered for selected patients with ACA or distal middle cerebral artery strokes. Further larger randomized investigation regarding the risk-benefit ratio for DMVO treatment is indicated.

Predictors of first pass effect and effect on outcomes in mechanical thrombectomy for basilar artery occlusion.

INTRODUCTION: For patients undergoing endovascular thrombectomy (EVT), those who are recanalized with a successful single pass (first pass effect, FPE) have better functional outcomes than those who do not. There is a scarcity of data regarding predictors of FPE in basilar artery occlusion (BAO). We aim to determine what characteristics may predict FPE for posterior circulation thrombectomies in a cohort of patients undergoing EVT for BAO. METHODS: We reviewed prospectively-collected data for patients presenting to a comprehensive stroke center with BAO between December 2015 and April 2019. Patients were included in this study if they underwent manual aspiration thrombectomy for BAO. Patients were excluded if they had occlusions of the posterior cerebral or vertebral arteries or if they had tandem lesions. Patients were stratified by whether FPE or modified FPE (mFPE) was achieved, and multivariate logistic regression analyses were performed to identify predictors of FPE and the effect of FPE on clinical outcome. RESULTS: 100 patients with BAO underwent thrombectomy. Mean age was 64.7 ± 16.7, 42% were female, and median NIHSS was 20 (IQR 11-27). 33% met criteria for FPE and 60% for mFPE. Univariate analysis identified female gender, lack of IV-tPA use, pcASPECTS, atrial fibrillation, and hyperlipidemia as possible predictors of FPE. On multivariate analysis, age, pcASPECTs, atrial fibrillation, hyperlipidemia and IV-tPA use were not independent predictors of FPE or mFPE. Female gender was an independent predictor of mFPE (p = 0.02), but not FPE (p = 0.18). FPE was a predictor of mRS 0-2 at 90 days (p = 0.04). Predictors of mortality were age (p < 0.01), baseline NIHSS (p < 0.01) and mFPE (p = 0.01). CONCLUSION: In this cohort analysis of 100 patients with basilar artery occlusion undergoing manual aspiration thrombectomy, female gender was associated with mFPE but not FPE. Previously-reported anterior circulation FPE predictors including age, ASPECTS and atrial fibrillation were not predictors of FPE in this cohort of patients with BAO.

Endovascular Thrombectomy Eligibility in the 0-24-Hour Time Window at a Large Academic Center in India.

Background: The data regarding patients eligible for endovascular thrombectomy (EVT), especially in the developing world is lacking. Objective: To determine the proportion of patients with acute ischemic stroke (AIS) who are eligible for EVT in the 0-24-h time window. Materials and Methods: We performed a retrospective cohort study using prospectively collected AIS data between July 2017 and September 2019. Demographic, clinical, and management information were analyzed. EVT eligibility was explored using the following criteria: National Institutes of Health Stroke Scale (NIHSS) score ≥6, presence of anterior circulation large-vessel occlusion (ACLVO), Alberta stroke program early Computerized Tomography score (ASPECTS) ≥6, baseline modified Rankin Scale (mRS) score 0-2, and within 24 h of time last seen well (TLSW). EVT-eligible patients were further evaluated for in-hospital course and outcomes. Results: In the study period of 27 months, there were 221 patients with AIS who presented within 24 h. The mean age of the patients was 54.4 (16.0) years and 66.1% (146) were males. A majority (61.5% [136/221]) arrived within 6 h of TLSW. Of these, 81.6% (111/136) presented in the time window for thrombolysis (0-4.5 h). The patients with NIHSS ≥6 and ACLVO constituted 41.2% (91/221) of the patients. AIS eligible for EVT constituted 19.5% (43/221) of the patients. Conclusion: In our study, the proportion of AIS eligible for endovascular thrombectomy was comparable to the developed world. These data predict a large potential for the late-window EVT in India.

Expedited Management of Low-Risk Transient Ischemic Attack Patients: The "Fast-Track" TIA Protocol.

OBJECTIVES: Transient ischemic attack (TIA) serves a precursor for an acute ischemic stroke (AIS); however, not all TIA patients harbor the same risk for subsequent AIS. We aimed to investigate expediting outpatient management of low-risk TIA patients (ABCD: Giles and Rothwell, 2007 score ≤ 3) via our "Fast-Track" TIA Protocol (FTTP). MATERIALS AND METHODS: A retrospective analysis was performed on patients who presented to our academic network 04/2020 - 2/2021. Patients who presented with ABCD: Giles and Rothwell, 2007 scores ≤ 3 without large vessel occlusion or flow limiting stenosis were eligible for the FTTP. These patients were discharged on dual antiplatelet therapy and statin and received prescriptions for transthoracic echo, holter monitor, LDL, and A1c along with a scheduled follow-up appointment 30 days from presentation. RESULTS: 182 consecutive patients were evaluated during this period, 21 (11%) were excluded from analysis due to NIHSS > 0 and/or infarct present on MRI. 35 (22%) patients qualified for FTTP and were directly discharged from the ED. Median ABCD2 score was 2 for the discharge group and 4 for the admitted group. There was a significant difference with respect to age and hypertension. Additionally, the FTTP patient population were more likely to be smokers than the admitted patient population. 3 FTTP patients re-presented to the ED, but none of them suffered a symptomatic stroke. CONCLUSIONS: A FTTP demonstrated feasibility and safety with low rates of re-presentation and ischemic stroke. Further research is warranted to determine an optimal patient population that can be safely managed in an outpatient setting.

Decreased DNA Methylation of RGMA is Associated with Intracranial Hypertension After Severe Traumatic Brain Injury: An Exploratory Epigenome-Wide Association Study.

BACKGROUND: Cerebral edema and intracranial hypertension are major contributors to unfavorable prognosis in traumatic brain injury (TBI). Local epigenetic changes, particularly in DNA methylation, may influence gene expression and thus host response/secondary injury after TBI. It remains unknown whether DNA methylation in the central nervous system is associated with cerebral edema severity or intracranial hypertension post TBI. We sought to identify epigenome-wide DNA methylation patterns associated with these forms of secondary injury after TBI. METHODS: We obtained genome-wide DNA methylation profiles of DNA extracted from ventricular cerebrospinal fluid samples at three different postinjury time points from a prospective cohort of patients with severe TBI (n = 89 patients, 254 samples). Cerebral edema and intracranial pressure (ICP) measures were clustered to generate composite end points of cerebral edema and ICP severity. We performed an unbiased epigenome-wide association study (EWAS) to test associations between DNA methylation at 419,895 cytosine-phosphate-guanine (CpG) sites and cerebral edema/ICP severity categories. Given inflated p values, we conducted permutation tests for top CpG sites to filter out potential false discoveries. RESULTS: Our data-driven hierarchical clustering across six cerebral edema and ICP measures identified two groups differing significantly in ICP based on the EWAS-identified CpG site cg22111818 in RGMA (Repulsive guidance molecule A, permutation p = 4.20 × 10-8). At 3-4 days post TBI, patients with severe intracranial hypertension had significantly lower levels of methylation at cg22111818. CONCLUSIONS: We report a novel potential relationship between intracranial hypertension after TBI and an acute, nonsustained reduction in DNA methylation at cg22111818 in the RGMA gene. To our knowledge, this is the largest EWAS in severe TBI. Our findings are further strengthened by previous findings that RGMA modulates axonal repair in other central nervous system disorders, but a role in intracranial hypertension or TBI has not been previously identified. Additional work is warranted to validate and extend these findings, including assessment of its possible role in risk stratification, identification of novel druggable targets, and ultimately our ability to personalize therapy in TBI.

Causes, Predictors, and Timing of Early Neurological Deterioration and Symptomatic Intracranial Hemorrhage After Administration of IV tPA.

BACKGROUND: Acute ischemic stroke (AIS) is a major contributor toward healthcare-associated costs and services. Symptomatic intracranial hemorrhage (sICH) and early neurologic decline (END), defined as a National Health Institute Stroke Scale score decline of ≥ 4 within 24 h (with or without sICH), remain major concerns when administering intravenous tissue plasminogen activator (IV tPA) despite improved functional neurologic outcomes with its use. Given these risks, current guidelines recommend comprehensive stroke care (most often in an intensive care unit setting) for 24 h posttreatment. However, a number of patients may remain stable after IV tPA and thus not require such intensive resources. We sought to determine causes of END, along with timing and predictors of both sICH and END, to identify patients at lower risk of neurological deterioration and those suitable for earlier transition to a lower level of care. METHODS: This present study analyzed patients with AIS that presented within 4.5 h of being last seen well and received IV tPA. Baseline demographic, clinical, and radiographic findings were collected. Outcomes included END from any cause, parenchymal hemorrhage (PH1 or PH2), sICH, and mortality at 90 days. RESULTS: A total of 1238 patients with AIS without acute treatment of large vessel occlusion received IV tPA. 9.4% (116) had presence of any degree of ICH on noncontrast computed tomography head and 7.4% (91) experienced associated END. 2.7% (33) of patients experienced sICH, while 6.7% (83) experienced asymptomatic ICH. Of the patients with END, 63.7% did not have ICH. Predictive factors at presentation for END included an older age (72.6 ± 16.1 vs. 69.1 ± 14.8, p = 0.03), history of tobacco use (odds ratio [OR] 2.1 [1.1-4.3], p = 0.04), and hyperlipidemia (OR 1.7 [1.1-2.8], p = 0.02), along with the presence of an untreated large vessel occlusion (OR 2.1 [1.4-3.1], p = 0.02). Most END occurred within a mean time of 242 ± 251 min (4 ± 4 h). Because of the small proportion of patients suffering from sICH (33), predictors could not be determined; however, for patients with any ICH, predictive factors included an older age (74.6 ± 12.4 vs. 68.8 ± 15.1, p = 0.001), higher baseline National Health Institute Stroke Scale score (14.6 ± 7.3 vs. 10.8 ± 7.9, p = 0.002), and higher baseline glucose levels (155.1 ± 87.5 vs. 140.4 ± 70.5, p = 0.04). CONCLUSIONS: In this study, only a small proportion suffered from either sICH and/or END, typically within 12 h of tPA administration. These findings may support earlier deescalation of higher acuity monitoring in clinically stable post-IV tPA patients without large vessel occlusion.

Fast and slow progressors of infarct growth in basilar artery occlusion strokes.

BACKGROUND: Heterogeneity in the infarct growth rate among anterior circulation large vessel occlusion (LVO) strokes has triage and treatment implications. Such data are lacking for basilar artery occlusion (BAO) strokes. We aim to describe the variability in brainstem infarct volume at presentation and compute the distribution of the infarct growth rate (IGR) and rate of loss of neurons during BAO strokes. METHODS: A retrospective review of consecutive patients with BAO stroke with pretreatment MRI was performed. Ischemic core volume was manually calculated (product of slice thickness and sum of area of region of interests) for the brainstem lesion. The distribution of various brainstem infarct volume groups was analyzed and the IGR (including rate of loss of neurons) was computed. RESULTS: Fifty-nine patients were included. Mean age was 64±13 and 34% were men. Mean National Institutes of Health Stroke Scale score was 20±11 and time to MRI was 9±5 hours. Mean brainstem ischemic core volume was 4.5±4.6 mL. According to predefined thresholds, 13% and 6% of patients with BAO stroke in the 0-6 hour time window were fast (5-10 mL) and ultra-fast progressors (>10 mL), respectively, and 14% of patients in the 6-24 hour time window were slow progressors (<1 mL). Median and mean rate of loss of neurons was 146 300 neurons/min and 261 300 (±400 000) neurons/min, respectively, and ranged from <19 400 to >2.12 million. CONCLUSION: Approximately 14% of BAO strokes are slow progressors and 19% are fast/ultra-fast progressors, with the rate of loss of neurons ranging from <19 000 to >2.1 million/min. Large heterogeneity exists in brainstem infarct volume at presentation and IGR among patients with BAO stroke.

First Pass Effect With Neurothrombectomy for Acute Ischemic Stroke: Analysis of the Systematic Evaluation of Patients Treated With Stroke Devices for Acute Ischemic Stroke Registry.

BACKGROUND AND PURPOSE: Achieving complete revascularization after a single pass of a mechanical thrombectomy device (first pass effect [FPE]) is associated with good clinical outcomes in patients with acute ischemic stroke due to large vessel occlusion. We assessed patient characteristics, outcomes, and predictors of FPE among a large real-world cohort of patients (Systematic Evaluation of Patients Treated with Stroke Devices for Acute Ischemic Stroke registry). METHODS: Demographics, clinical outcomes, and procedural characteristics were analyzed among patients in whom FPE (modified Thrombolysis in Cerebral Infarction 2c/3 after first pass) was achieved versus those requiring multiple passes (MP). Modified FPE and modified MP included patients achieving modified Thrombolysis in Cerebral Infarction 2B-3. Primary outcomes included 90-day modified Rankin Scale (mRS) score and mortality. RESULTS: Among 984 Systematic Evaluation of Patients Treated with Stroke Devices for Acute Ischemic Stroke patients, 930 had complete 90-day follow-up. FPE was achieved in 40.5% (377/930) of patients and MP in 20.0% (186/930). Baseline characteristics were similar across all groups. The FPE group had fewer internal carotid artery occlusions compared with MP (P=0.029). The FPE group had faster puncture to recanalization time (P≤0.001), higher rates of 90-day mRS score of 0 to 1 (52.6% versus 38.6%, P=0.003), mRS score of 0 to 2 (65.4% versus 52.0%, P=0.003), and lower 90-day mortality compared with the MP group (12.0% versus 18.7%, P=0.038). Similarly, compared with modified MP patients, the modified FPE group had fewer internal carotid artery occlusions (P=0.004), faster puncture to recanalization time (P≤0.001), and higher rates of 90-day mRS score of 0 to 1 (P=0.002) and mRS score of 0 to 2 (P=0.003). CONCLUSIONS: Our findings demonstrate that FPE and modified FPE are associated with superior clinical outcomes.

Endovascular thrombectomy time metrics in the era of COVID-19: observations from the Society of Vascular and Interventional Neurology Multicenter Collaboration.

BACKGROUND: Unprecedented workflow shifts during the coronavirus disease 2019 (COVID-19) pandemic have contributed to delays in acute care delivery, but whether it adversely affected endovascular thrombectomy metrics in acute large vessel occlusion (LVO) is unknown. METHODS: We performed a retrospective review of observational data from 14 comprehensive stroke centers in nine US states with acute LVO. EVT metrics were compared between March to July 2019 against March to July 2020 (primary analysis), and between state-specific pre-peak and peak COVID-19 months (secondary analysis), with multivariable adjustment. RESULTS: Of the 1364 patients included in the primary analysis (51% female, median NIHSS 14 [IQR 7-21], and 74% of whom underwent EVT), there was no difference in the primary outcome of door-to-puncture (DTP) time between the 2019 control period and the COVID-19 period (median 71 vs 67 min, P=0.10). After adjustment for variables associated with faster DTP, and clustering by site, there remained a trend toward shorter DTP during the pandemic (ßadj=-73.2, 95% CI -153.8-7.4, Pp=0.07). There was no difference in DTP times according to local COVID-19 peaks vs pre-peak months in unadjusted or adjusted multivariable regression (ßadj=-3.85, 95% CI -36.9-29.2, P=0.80). In this final multivariable model (secondary analysis), faster DTP times were significantly associated with transfer from an outside institution (ßadj=-46.44, 95% CI -62.8 to - -30.0, P<0.01) and higher NIHSS (ßadj=-2.15, 95% CI -4.2to - -0.1, P=0.05). CONCLUSIONS: In this multi-center study, there was no delay in EVT among patients treated for intracranial occlusion during the COVID-19 era compared with the pre-COVID era.

Thrombectomy With and Without Computed Tomography Perfusion Imaging in the Early Time Window: A Pooled Analysis of Patient-Level Data.

BACKGROUND: The optimal imaging paradigm for endovascular thrombectomy (EVT) patient selection in early time window (0-6 hours) treated acute ischemic stroke patients remains uncertain. We aimed to compare post-EVT outcomes between patients who underwent prerandomization basic (noncontrast computed tomography [CT], CT angiography only) versus additional advanced imaging (computed tomography perfusion [CTP] imaging) and to determine the association of performance of prerandomization CTP imaging with clinical outcomes. METHODS: The HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) pooled patient-level data from randomized controlled trials comparing EVT with usual care for acute ischemic stroke due to anterior circulation large vessel occlusion. Good functional outcome, defined as modified Rankin Scale score 0 to 2 at 90 days, was compared between randomized patients with and without CTP baseline imaging. Univariable and multivariable binary logistic regression analysis was performed to determine the association of baseline CTP imaging and good functional outcome. RESULTS: We analyzed 1348 patients 610 (45.3%) of whom underwent CTP prerandomization. The benefit of EVT compared with best medical management was maintained irrespective of the baseline imaging paradigm (90-day modified Rankin Scale score 0-2 in EVT versus control patients: with CTP: 46.0% (137/298) versus 28.9% (88/305), without CTP: 44.1% (162/367) versus 27.3% (100/366). Performance of CTP baseline imaging compared with baseline noncontrast CT and CT angiography only yielded similar rates of good outcome (odds ratio, 1.05 [95% CI, 0.82-1.33], adjusted odds ratio, 1.04, [95% CI, 0.80-1.35]). CONCLUSIONS: Rates of good functional outcome were similar among patients in whom CTP was or was not performed, and EVT treatment effect in the 0- to 6-hour time window was similar in patients with and without baseline CTP imaging.