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INTRODUCTION: The real-world evolution of management and outcomes of patients with unruptured brain arteriovenous malformations (AVMs) has not been well-delineated following the ARUBA trial findings of no general advantage of initial interventional (surgical/endovascular/radiotherapy) vs. initial conservative medical therapy. METHODS: We analyzed the National Inpatient Sample from 2009-2018, capturing 20% of all admissions in the U.S. Validated ICD-9 and -10 codes defined brain AVMs, comorbidities, and the use of interventional modalities. Analyses were performed by year and for the dichotomized periods of pre-ARUBA (2009-2013) vs. post-ARUBA (2014-2018). RESULTS: Among the national projected 88,037 AVM admissions, 72,812 (82.7%) were unruptured AVMs and 15,225 (17.3%) were ruptured AVMs. Among uAVMs, 51.4% admitted pre-ARUBA and 48.6% in post-ARUBA period. The post-ARUBA patients were mildly older (median age 53.3 vs. 51.8 (p = 0.001) and had more comorbidities including hypertension, diabetes, obesity, renal impairment, and smoking. Before the first platform report of ARUBA (2009-2012), rates of use of interventional treatments during uAVM admissions trended up from 31.8% to 35.4%. Thereafter, they declined significantly to 26.4% in 2018 (p = 0.02). The decline was driven by a reduction in the frequency of endovascular treatment from 18.8% to 13.9% and inpatient stereotactic radiosurgery from 0.5% to 0.1%. No change occurred in the frequency of microsurgery or combined endovascular and surgical approaches. Adjusted multivariable model of uAVMs showed increased odds of discharge to a long-term inpatient facility or in-hospital death [OR 1.14 (1.02-1.28), p = 0.020] in post-ARUBA. A significantly increased proportion of ruptured AVMs from 17.0% to 23.3% was observed consistently in post-ARUBA. CONCLUSION: Nationwide practice in the management of unruptured AVMs changed substantially with the publication of the ARUBA trial in a durable and increasing manner. Fewer admissions with the interventional treatment of unruptured AVMs occurred, and a corresponding increase in admission for ruptured AVMs transpired, as expected with a strategy of watchful waiting and treatment only after an index bleeding event. Further studies are needed to determine whether these trends can be considered to be ARUBA trial effect or are merely coincidental.

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Background and Purpose: Although National Institutes of Health Stroke Scale scores provide an objective measure of clinical deficits, data regarding the impact of neglect or language impairment on outcomes after mechanical thrombectomy (MT) is lacking. We assessed the frequency of neglect and language impairment, rate of their rescue by MT, and impact of rescue on clinical outcomes. Methods: This is a retrospective analysis of a prospectively collected database from a comprehensive stroke center. We assessed right (RHS) and left hemispheric strokes (LHS) patients with anterior circulation large vessel occlusion undergoing MT to assess the impact of neglect and language impairment on clinical outcomes, respectively. Safety and efficacy outcomes were compared between patients with and without rescue of neglect or language impairment. Results: Among 324 RHS and 210 LHS patients, 71% of patients presented with neglect whereas 93% of patients had language impairment, respectively. Mean age was 71±15, 56% were females, and median National Institutes of Health Stroke Scale score was 16 (12­20). At 24 hours, MT resulted in rescue of neglect in 31% of RHS and rescue of language impairment in 23% of LHS patients, respectively. RHS patients with rescue of neglect (56% versus 34%, P<0.001) and LHS patients with rescue of language impairment (64 % versus 25%, P<0.01) were observed to have a higher rate of functional independence compared to patients without rescue. After adjusting for confounders including 24-hour National Institutes of Health Stroke Scale, rescue of neglect among RHS patients was associated with functional independence (P=0.01) and lower mortality (P=0.01). Similarly, rescue of language impairment among LHS patients was associated with functional independence (P=0.02) and lower mortality (P=0.001). Conclusions: Majority of LHS-anterior circulation large vessel occlusion and of RHS-anterior circulation large vessel occlusion patients present with the impairment of language and neglect, respectively. In comparison to 24-hour National Institutes of Health Stroke Scale, rescue of these deficits by MT is an independent and a better predictor of functional independence and lower mortality.

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Background and Purpose: Patient selection for thrombectomy of acute ischemic stroke caused by large vessel occlusion in the delayed time window (>6 hours) is dependent on delineation of clinical-core mismatch or radiological target mismatch using perfusion imaging. Selection paradigms not involving advanced imaging and software processing may reduce time to treatment and broaden eligibility. We aim to develop a conversion factor to approximately determine the volume of hypoperfused tissue using the National Institutes of Health Stroke Scale (NIHSS) score (clinically approximated hypoperfused tissue [CAT] volume) and explore its ability to identify patients eligible for thrombectomy in the late-time window. Methods: We performed a retrospective analysis of anterior circulation large vessel occlusion strokes at 3 comprehensive stroke centers. Demographic, clinical, and imaging (computed tomography perfusion processed using RAPID, IschemaView) information was analyzed. A conversion factor, which is a multiple of the NIHSS score (for NIHSS score <10 and ≥10), was derived from an initial cohort to calculate CAT volumes. Accuracy of CAT-based thrombectomy eligibility criteria (using CAT volume instead of Tmax >6 seconds volume) was tested using DEFUSE-3 criteria (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) eligibility as a gold standard in an independent cohort. Results: Of the 309 large vessel occlusion strokes (age, 70±14, 46% male, median NIHSS 16 [12­20]) included in this study, 38% of patients arrived beyond 6 hours of time from last known well. Conversion factors derived (derivation cohort-center A: 187) based on median values of Tmax>6 second volume for NIHSS score <10 subgroup was 15 and for NIHSS score ≥10 subgroup was 6. Subsequently calculated CAT volume­based eligibility criteria yielded a sensitivity of 100% and specificity of 92% in detecting DEFUSE-3 eligible patients (area under the curve, 0.92 [95% CI, 0.82­1]) in the validation cohort (center B and C:122). Conclusions: Clinical severity of stroke (NIHSS score) may be used to calculate the volume of hypoperfused tissue during large vessel occlusion stroke. CAT volumes for NIHSS score <10 (using a factor of 15) and ≥10 (using a factor of 6) subgroups can accurately identify DEFUSE-3-eligible patients.

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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.

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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.

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BACKGROUND AND PURPOSE: The results of the DAWN trial (Diffusion-Weighted Imaging or Computerized Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) support the benefit of endovascular therapy in patients presenting beyond the 6-hour time window with anterior circulation large vessel occlusions. The impact of these results with respect to additional number of eligible patients in clinical practice remains unknown. METHODS: A retrospective review of ischemic stroke admissions to a single DAWN trial-participating comprehensive stroke center was performed during the DAWN enrollment period (November 2014 to February 2017) to identify patients meeting criteria for DAWN and DEFUSE-3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke-3) eligibility. Patients presenting beyond 6 hours were further investigated to clarify reasons for trial exclusion. RESULTS: Of the 2667 patients with acute ischemic stroke admitted within the study period, 30% (n=792) presented within the 6- to 24-hour time window, and 47% (n=1242) had a National Institutes of Health Stroke Scale ≥6. Further clinical trial-specific selection criteria were applied based on the presence of large vessel occlusion, baseline modified Rankin Scale score, core infarct, and perfusion imaging (when available). There were 45 patients who met all DAWN trial criteria and 47 to 58 patients who would meet DEFUSE-3 trial criteria. Thirty-three percent of DAWN-eligible patients are DEFUSE-3 ineligible. CONCLUSIONS: 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.

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BACKGROUND AND PURPOSE: Mechanical thrombectomy with stent retrievers has become standard of care for treatment of acute ischemic stroke patients because of large vessel occlusion. The STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) aimed to assess whether similar process timelines, technical, and functional outcomes could be achieved in a large real world cohort as in the randomized trials. METHODS: STRATIS was designed to prospectively enroll patients treated in the United States with a Solitaire Revascularization Device and Mindframe Capture Low Profile Revascularization Device within 8 hours from symptom onset. The STRATIS cohort was compared with the interventional cohort of a previously published SEER patient-level meta-analysis. RESULTS: A total of 984 patients treated at 55 sites were analyzed. The mean National Institutes of Health Stroke Scale score was 17.3. Intravenous tissue-type plasminogen activator was administered in 64.0%. The median time from onset to arrival in the enrolling hospital, door to puncture, and puncture to reperfusion were 138, 72, and 36 minutes, respectively. The Core lab-adjudicated modified Thrombolysis in Cerebral Infarction ≥2b was achieved in 87.9% of patients. At 90 days, 56.5% achieved a modified Rankin Scale score of 0 to 2, all-cause mortality was 14.4%, and 1.4% suffered a symptomatic intracranial hemorrhage. The median time from emergency medical services scene arrival to puncture was 152 minutes, and each hour delay in this interval was associated with a 5.5% absolute decline in the likelihood of achieving modified Rankin Scale score 0 to 2. CONCLUSIONS: This largest-to-date Solitaire registry documents that the results of the randomized trials can be reproduced in the community. The decrease of clinical benefit over time warrants optimization of the system of care. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02239640.

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