Thrombectomy appears to be safe and feasible in patients with acute ischemic stroke due to LVO meeting all DAWN trial criteria but treated beyond 24 hours of TLKW with outcomes comparable to patients in the DAWN trial intervention arm. Further studies are warranted to validate these findings.

Of all patients with acute ischemic stroke presenting to a single comprehensive stroke center, 1.7% of patients qualified for DAWN clinical trial enrollment with an additional 0.6% to 1% qualifying for the DEFUSE-3 trial. These data predict an increase in thrombectomy utilization with important implications for comprehensive stroke center resource optimization and stroke systems of care.

Approximately 70% (n=142) of the 204 patients presenting 6-24 hours after last known well with NIH Stroke Scale score ≥6 and harboring an ACLVO are DAWN and/or DEFUSE-3 ineligible, most commonly due to large infarct burden (38%). 26% (n=37) of trial ineligible patients with large vessel occlusion strokes received off-label ET and 30% of them achieved functional independence (modified Rankin Scale 0-2) at 90 days. Rates of symptomatic intracranial hemorrhage and mortality were 8% and 24%, respectively CONCLUSION: Trial ineligible patients with large vessel occlusion strokes receiving off-label ET achieved outcomes comparable to DAWN and DEFUSE-3 eligible patients. Patients aged <80 years are most likely to benefit from ET in this subgroup. These data indicate a larger population of patients who can potentially benefit from ET in the expanded time window if more permissive criteria are applied.

Background and Purpose— Fast and slow progressors of infarct growth due to anterior circulation large vessel occlusion are commonly observed in clinical practice. We aimed to estimate the prevalence and temporal distribution of fast and slow progressors among anterior circulation large vessel occlusion patients diagnosed within 24 hours of stroke onset. Methods— Single-center retrospective study of all patients with anterior circulation large vessel occlusion who underwent baseline computed tomographic perfusion or magnetic resonance imaging within 24 hours of stroke onset. Prevalence was determined for fast progressors (ischemic core >70 mL, <6 hours of stroke onset) and slow progressors (ischemic core ≤30 mL, >6–24 hours of stroke onset). Results— One hundred eighty-five patients were included. The median time interval from stroke onset to baseline core imaging was 7.6 hours (interquartile range, 3.9–13.2), and median core volume was 17 mL (range, 0–405). Patients had core volume ≤70 mL in 72% of cases in the overall cohort. The prevalence of fast progressors was 25% (95% CI, 17%–37%) and reached 40% (95% CI, 24%–59%) between 3 and 4.5 hours after stroke onset. The prevalence of slow progressors was 55% (95% CI, 46%–64%) and was similar across time intervals beyond 6 hours after stroke onset. Conclusions— Most anterior circulation large vessel occlusion patients had small-to-moderate ischemic core volume, irrespective of early or delayed presentation within 24 hours of stroke onset. Fast progressors were highly prevalent between 3 and 4.5 hours after stroke onset.

Background: The COVID-19 pandemic's impact on stroke care is two-fold À À direct impact of the infection and indirect impact on non-COVID-19 diseases. Anecdotal evidence and clinical observation suggest that there is a decrease in the number of patients presenting with stroke during the pandemic. We aim to understand the impact of the COVID-19 pandemic on the utilization of stroke emergency services on a single comprehensive stroke center (CSC). Methods: We performed a retrospective analysis of a prospectively maintained database and compared all emergency department (ED) encounters, acute stroke admissions (including TIA), and thrombectomy cases admitted in March 2017-2019 to patients admitted in March 2020 at a comprehensive stroke center. Results: Number of total ED encounters (22%, p=0.005), acute ischemic strokes (40%, p=0.001), and TIAs (60%, p=0.163) decreased between March of 2017À2019 compared to March of 2020. The number of patients undergoing EVT in March 2020 was comparable to March 2017À2019 (p=0.430). Conclusion: A pandemic-related stay-at-home policy reduces the utilization of stroke emergency services at a CSC. This effect appears to be more prominent for ED encounters, all stroke admissions and TIAs, and less impactful for severe strokes. Given the relatively low prevalence of COVID-19 cases in our region, this decrement is likely related to healthcare seeking behavior rather than capacity saturation.

Background and Purpose: The pandemic caused by the novel coronavirus disease 2019 (COVID-19) has led to an unprecedented paradigm shift in medical care. We sought to evaluate whether the COVID-19 pandemic may have contributed to delays in acute stroke management at comprehensive stroke centers. Methods: Pooled clinical data of consecutive adult stroke patients from 14 US comprehensive stroke centers (January 1, 2019, to July 31, 2020) were queried. The rate of thrombolysis for nontransferred patients within the Target: Stroke goal of 60 minutes was compared between patients admitted from March 1, 2019, and July 31, 2019 (pre–COVID-19), and March 1, 2020, to July 31, 2020 (COVID-19). The time from arrival to imaging and treatment with thrombolysis or thrombectomy, as continuous variables, were also assessed. Results: Of the 2955 patients who met inclusion criteria, 1491 were admitted during the pre–COVID-19 period and 1464 were admitted during COVID-19, 15% of whom underwent intravenous thrombolysis. Patients treated during COVID-19 were at lower odds of receiving thrombolysis within 60 minutes of arrival (odds ratio, 0.61 [95% CI, 0.38–0.98]; P =0.04), with a median delay in door-to-needle time of 4 minutes ( P =0.03). The lower odds of achieving treatment in the Target: Stroke goal persisted after adjustment for all variables associated with earlier treatment (adjusted odds ratio, 0.55 [95% CI, 0.35–0.85]; P <0.01). The delay in thrombolysis appeared driven by the longer delay from imaging to bolus (median, 29 [interquartile range, 18–41] versus 22 [interquartile range, 13–37] minutes; P =0.02). There was no significant delay in door-to-groin puncture for patients who underwent thrombectomy (median, 83 [interquartile range, 63–133] versus 90 [interquartile range, 73–129] minutes; P =0.30). Delays in thrombolysis were observed in the months of June and July. Conclusions: Evaluation for acute ischemic stroke during the COVID-19 period was associated with a small but significant delay in intravenous thrombolysis but no significant delay in thrombectomy time metrics. Taking steps to reduce delays from imaging to bolus time has the potential to attenuate this collateral effect of the pandemic.

Sulfonylurea-receptor-1(SUR1) and its associated transient-receptor-potential cation channel subfamily-M (TRPM4) channel are key contributors to cerebral edema and intracranial hypertension in traumatic brain injury (TBI) and other neurological disorders. Channel inhibition by glyburide is clinically promising. ABCC8 (encoding SUR1) singlenucleotide polymorphisms (SNPs) are reported as predictors of raised intracranial pressure (ICP). This project evaluated whether TRPM4 SNPs predicted ICP and TBI outcome. DNA was extracted from 435 consecutively enrolled severe TBI patients. Without a priori selection, all 11 TRPM4 SNPs available on the multiplex platform (Illumina:Human-Core-Exome v1.0) were genotyped spanning the 25 exon gene. A total of 385 patients were analyzed after quality control. Outcomes included ICP and 6 month Glasgow Outcome Scale (GOS) score. Proxy SNPs, spatial modeling, and functional predictions were determined using established software programs. rs8104571 (intron-20) and rs150391806 (exon-24) were predictors of ICP. rs8104571 heterozygotes predicted higher average ICP (b = 10.3 mm Hg, p = 0.00000029), peak ICP (b = 19.6 mm Hg, p = 0.0007), and proportion ICP >25 mm Hg (b = 0.16 p = 0.004). rs150391806 heterozygotes had higher mean (b = 7.2 mm Hg, p = 0.042) and peak (b = 28.9 mm Hg, p = 0.0015) ICPs. rs8104571, rs150391806, and 34 associated proxy SNPs in linkage-disequilibrium clustered downstream. This region encodes TRPM4's channel pore and a region postulated to juxtapose SUR1 sequences encoded by an ABCC8 DNA segment containing previously identified relevant SNPs. There was an interaction effect on ICP between rs8104571 and a cluster of predictive ABCC8 SNPs (rs2237982, rs2283261, rs11024286). Although not significant in univariable or a basic multivariable model, in an expanded model additionally accounting for injury pattern, computed tomographic (CT) appearance, and intracranial hypertension, heterozygous rs8104571 was associated with favorable 6 month GOS (odds ratio [OR] = 16.7, p = 0.007951). This trend persisted in a survivor-only subcohort (OR = 20.67, p = 0.0168). In this cohort, two TRPM4 SNPs predicted increased ICP with large effect sizes. Both clustered downstream, spanning a region encoding the channel pore and interacting with SUR1. If validated, this may guide risk stratification and eventually inform treatment-responder classification for SUR1-TRPM4 inhibition in TBI. Larger studies are warranted.

Background and Purpose— In the setting of acute ischemic stroke because of large-vessel occlusion (LVO) there is progressive loss of brain tissue which occurs in a time-dependent fashion previously quantified to be ≈1.9 million neurons per minute. However, this number represents an average and accumulating evidence suggests large individual variation. In this study, we aim to quantify the distribution and range in the rate of loss brain tissue across the entire spectrum of clinical phenotypes of anterior circulation LVO strokes encountered in clinical practice. Methods— Retrospective review of a prospectively acquired database of consecutive patients with anterior circulation stroke because of proximal LVO and appropriate ischemic core imaging was performed. Ischemic core volume was measured using automated software processing and time from last known well to imaging was recorded. Applying previously published methodology for brain loss quantification, we computed rate of brain tissue elements loss in proximal LVO stroke patients. Results— We studied 415 patients with internal carotid artery or middle cerebral artery (M1 segment) occlusion. Mean ischemic core volume was 50.4 mL and mean time to imaging from time from last known well (TLKW) was 8.7 hours, which is similar to previously published data, translates into a mean loss per minute of 2.03 million neurons, 14.8 billion synapses, and 12.8 km of myelinated fibers. However, the distribution of neuron loss was highly variable, ranging from <35 000 to >27 million cells per minute. Conclusions— Widely spread rates of infarct growth are observed in acute ischemic stroke because of proximal LVO with rate of neuron loss per minute ranging from <35 000 per minute in slow progressors to >27 million per minute in fast progressors, with a mean and median of 2 million and 0.9 million, respectively.