Neurovascular Complications of Iatrogenic Fusarium solani Meningitis.

A multinational outbreak of nosocomial fusarium meningitis occurred among immunocompetent patients who had undergone surgery with epidural anesthesia in Mexico. The pathogen involved had a high predilection for the brain stem and vertebrobasilar arterial system and was associated with high mortality from vessel injury. Effective treatment options remain limited; in vitro susceptibility testing of the organism suggested that it is resistant to all currently approved antifungal medications in the United States. To highlight the severe complications associated with fusarium infection acquired in this manner, we report data, clinical courses, and outcomes from 13 patients in the outbreak who presented with symptoms after a median delay of 39 days.

Rescue Therapy for Failed Mechanical Thrombectomy in Acute Ischemic Stroke: A Pooled Analysis of the Society of Vascular and Interventional Neurology Registry.

OBJECTIVE: We aimed to evaluate the association between rescue therapy (RT) and functional outcomes compared to medical management (MM) in patients presenting after failed mechanical thrombectomy (MT). METHODS: This cross-sectional study utilized prospectively collected and maintained data from the Society of Vascular and Interventional Neurology Registry, spanning from 2011 to 2021. The cohort comprised patients with large vessel occlusions (LVOs) with failed MT. The primary outcome was the shift in the degree of disability, as gauged by the modified Rankin Scale (mRS) at 90 days. Additional outcomes included functional independence (90-day mRS score of 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. RESULTS: Of a total of 7,018 patients, 958 presented failed MT and were included in the analysis. The RT group comprised 407 (42.4%) patients, and the MM group consisted of 551 (57.5%) patients. After adjusting for confounders, the RT group showed a favorable shift in the overall 90-day mRS distribution (adjusted common odds ratio = 1.79, 95% confidence interval [CI] = 1.32-2.45, p < 0.001) and higher rates of functional independence (RT: 28.8% vs MM: 15.7%, adjusted odds ratio [aOR] = 1.93, 95% CI = 1.21-3.07, p = 0.005) compared to the MM group. RT also showed lower rates of sICH (RT: 3.8% vs MM: 9.1%, aOR = 0.52, 95% CI = 0.28-0.97, p = 0.039) and 90-day mortality (RT: 33.4% vs MM: 45.5%, aOR = 0.61, 95% CI = 0.42-0.89, p = 0.009). INTERPRETATION: Our findings advocate for the utilization of RT as a potential treatment strategy for cases of LVO resistant to first-line MT techniques. Prospective studies are warranted to validate these observations and optimize the endovascular approach for failed MT patients. ANN NEUROL 2024;96:343-355.

Cervical Dissection in Patients With Tandem Lesions Is Associated With Distal Embolism and Lower Recanalization Success.

BACKGROUND: Tandem lesions consist of cervical internal carotid artery (ICA) stenosis or occlusion, most commonly of atherosclerosis or dissection etiology, plus a large vessel occlusion. In this study, we compare outcomes in patients with atherosclerosis versus dissection of the cervical ICA. METHODS: This multicenter retrospective cohort study includes data from tandem lesion patients who underwent endovascular treatment from 2015 to 2020. Atherosclerosis was defined as ICA stenosis/occlusion associated with a calcified lesion and dissection by the presence of a tapered or flame-shaped lesion and intramural hematoma. Primary outcome: 90-day functional independence (modified Rankin Scale score, 0-2); secondary outcomes: 90-day favorable shift in the modified Rankin Scale score, modified Thrombolysis in Cerebral Infarction score 2b-3, modified Thrombolysis in Cerebral Infarction score 2c-3, symptomatic intracranial hemorrhage, parenchymal hematoma type 2, petechial hemorrhage, distal embolization, early neurological improvement, and mortality. Analysis was performed with matching by inverse probability of treatment weighting. RESULTS: We included 526 patients (68 [59-76] years; 31% females); 11.2% presented dissection and 88.8%, atherosclerosis. Patients with dissection were younger, had lower rates of hypertension, hyperlipidemia, diabetes, and smoking history. They also exhibited higher rates of ICA occlusion, multiple stents (>1), and lower rates of carotid self-expanding stents. After matching and adjusting for covariates, there were no differences in 90-day functional independence. The rate of successful recanalization was significantly lower in the dissection group (adjusted odds ratio, 0.38 [95% CI, 0.16-0.91]; P=0.031), which also had significantly higher rates of distal emboli (adjusted odds ratio, 2.53 [95% CI, 1.15-5.55]; P=0.021). There were no differences in other outcomes. Acute ICA stenting seemed to increase the effect of atherosclerosis in successful recanalization. CONCLUSIONS: This study reveals that among patients with acute stroke with tandem lesions, cervical ICA dissection is associated with higher rates of distal embolism and lower rates of successful recanalization than atherosclerotic lesions. Using techniques to minimize the risk of distal embolism may mitigate this contrast. Further prospective randomized trials are warranted to fully understand these associations.

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.

Outcomes of Bridging Intravenous Thrombolysis Versus Endovascular Therapy Alone in Late-Window Acute Ischemic Stroke.

BACKGROUND: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well. METHODS: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT. RESULTS: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P<0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P=0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P=0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P=0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P=0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well. CONCLUSIONS: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.

Sex Differences in Outcomes of Late-Window Endovascular Stroke Therapy.

BACKGROUND: The association between sex and outcome after endovascular thrombectomy of acute ischemic stroke is unclear. The aim of this study was to compare the clinical and safety outcomes between men and women treated with endovascular thrombectomy in the late 6-to-24-hour window period. METHODS: This multicenter, retrospective observational cohort study included consecutive patients who underwent endovascular thrombectomy of anterior circulation stroke in the late window from 66 clinical sites in 10 countries from January 2014 to May 2022. The primary outcome was the 90-day ordinal modified Rankin Scale score. Secondary outcomes included 90-day functional independence (FI), return of Rankin (RoR) to prestroke baseline, FI or RoR, symptomatic intracranial hemorrhage, and mortality. Multivariable and inverse probability of treatment weighting methods were used. We explored the interaction of sex with baseline characteristics on the outcomes ordinal modified Rankin Scale and FI or RoR. RESULTS: Of 1932 patients, 1055 were women and 877 were men. Women were older (77 versus 69 years), had higher rates of atrial fibrillation, hypertension, and greater prestroke disability, but there was no difference in baseline National Institutes of Health Stroke Scale score. Inverse probability of treatment weighting analysis showed no difference between women and men in ordinal modified Rankin Scale (odds ratio, 0.98 [95% CI, 0.79-1.21]), FI or RoR (odds ratio, 0.98 [95% CI, 0.78-1.22]), severe disability or mortality (odds ratio, 0.99 [95% CI, 0.80-1.23]). The multivariable analysis of the above end points was concordant. There were no interactions between baseline characteristics and sex on the outcomes of ordinal modified Rankin Scale and FI or RoR. CONCLUSIONS: In late presenting patients with anterior circulation stroke treated with endovascular thrombectomy in the 6 to 24-hour window, there was no difference in clinical or safety outcomes between men and women.

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.

A mitochondrial protein compendium elucidates complex I disease biology.

Mitochondria are complex organelles whose dysfunction underlies a broad spectrum of human diseases. Identifying all of the proteins resident in this organelle and understanding how they integrate into pathways represent major challenges in cell biology. Toward this goal, we performed mass spectrometry, GFP tagging, and machine learning to create a mitochondrial compendium of 1098 genes and their protein expression across 14 mouse tissues. We link poorly characterized proteins in this inventory to known mitochondrial pathways by virtue of shared evolutionary history. Using this approach, we predict 19 proteins to be important for the function of complex I (CI) of the electron transport chain. We validate a subset of these predictions using RNAi, including C8orf38, which we further show harbors an inherited mutation in a lethal, infantile CI deficiency. Our results have important implications for understanding CI function and pathogenesis and, more generally, illustrate how our compendium can serve as a foundation for systematic investigations of mitochondria.

Underutilization of Endovascular Therapy in Black Patients With Ischemic Stroke: An Analysis of State and Nationwide Cohorts.

BACKGROUND AND PURPOSE: Endovascular therapy (EVT) is a very effective treatment but relies on specialized capabilities that are not available in every hospital where acute ischemic stroke is treated. Here, we assess whether access to and utilization of this therapy has extended uniformly across racial and ethnic groups. METHODS: We conducted a retrospective, population-based study using the 2019 Texas Inpatient Public Use Data File. Acute ischemic stroke cases and EVT use were identified using the International Classification of Diseases, Tenth Revision (ICD-10) diagnosis and procedure codes. We examined EVT utilization by race/ethnicity and performed patient- and hospital-level analyses. To validate state-specific findings, we conducted patient-level analyses using the 2017 National Inpatient Sample for national estimates. To assess independent associations between race/ethnicity and EVT, multivariable modified Poisson regressions were fitted and adjusted relative risks were estimated accounting for patient risk factors and socioeconomic characteristics. RESULTS: Among 40 814 acute ischemic stroke cases in Texas in 2019, 54% were White, 17% Black, and 21% Hispanic. Black patients had similar admissions to EVT-performing hospitals and greater admissions to comprehensive stroke centers (CSCs) compared with White patients (EVT 62% versus 62%, P=0.21; CSCs 45% versus 39%, P<0.001) but had lower EVT rates (4.1% versus 5.3%; adjusted relative risk, 0.76 [0.66-0.88]; P<0.001). There were no differences in EVT rates between Hispanic and White patients. Lower rates of EVT among Black patients were consistent in the subgroup of patients who arrived in early time windows and received intravenous recombinant tissue-type plasminogen activator (adjusted relative risk, 0.77 [0.61-0.98]; P=0.032) and the subgroup of those admitted to EVT-performing hospitals in both non-CSC (3.0% versus 5.5, P<0.001) and CSC hospitals (7.9% versus 10.4%, P<0.001) while there were no differences between Whites and Hispanic patients. Nationwide sample data confirmed this finding of lower utilization of EVT among Black patients (adjusted relative risk, 0.87 [0.77-0.98]; P=0.024). CONCLUSIONS: We found no evidence of disparity in presentation to EVT-performing hospitals or CSCs; however, lower rates of EVT were observed in Black patients.

Machine Learning Automated Detection of Large Vessel Occlusion From Mobile Stroke Unit Computed Tomography Angiography.

BACKGROUND: Prehospital automated large vessel occlusion (LVO) detection in Mobile Stroke Units (MSUs) could accelerate identification and treatment of patients with LVO acute ischemic stroke. Here, we evaluate the performance of a machine learning (ML) model on CT angiograms (CTAs) obtained from 2 MSUs to detect LVO. METHODS: Patients evaluated on MSUs in Houston and Los Angeles with out-of-hospital CTAs were identified. Anterior circulation LVO was defined as an occlusion of the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or anterior cerebral artery vessels and determined by an expert human reader. A ML model to detect LVO was trained and tested on independent data sets consisting of in-hospital CTAs and then tested on MSU CTA images. Model performance was determined using area under the receiver-operator curve statistics. RESULTS: Among 68 patients with out-of-hospital MSU CTAs, 40% had an LVO. The most common occlusion location was the middle cerebral artery M1 segment (59%), followed by the internal carotid artery (30%), and middle cerebral artery M2 (11%). Median time from last known well to CTA imaging was 88.0 (interquartile range, 59.5-196.0) minutes. After training on 870 in-hospital CTAs, the ML model performed well in identifying LVO in a separate in-hospital data set of 441 images with area under receiver-operator curve of 0.84 (95% CI, 0.80-0.87). ML algorithm analysis time was under 1 minute. The performance of the ML model on the MSU CTA images was comparable with area under receiver-operator curve 0.80 (95% CI, 0.71-0.89). There was no significant difference in performance between the Houston and Los Angeles MSU CTA cohorts. CONCLUSIONS: In this study of patients evaluated on MSUs in 2 cities, a ML algorithm was able to accurately and rapidly detect LVO using prehospital CTA acquisitions.

Endovascular Treatment of Acute Ischemic Stroke With the Penumbra System in Routine Practice: COMPLETE Registry Results.

BACKGROUND AND PURPOSE: The purpose of the COMPLETE (International Acute Ischemic Stroke Registry With the Penumbra System Aspiration Including the 3D Revascularization Device) registry was to evaluate the generalizability of the safety and efficacy of the Penumbra System (Penumbra, Inc, Alameda) in a real-world setting. METHODS: COMPLETE was a global, prospective, postmarket, multicenter registry. Patients with large vessel occlusion-acute ischemic stroke who underwent mechanical thrombectomy using the Penumbra System with or without the 3D Revascularization Device as frontline approach were enrolled at 42 centers (29 United States, 13 Europe) from July 2018 to October 2019. Primary efficacy end points were successful postprocedure angiographic revascularization (modified Thrombolysis in Cerebral Infarction ≥2b) and 90-day functional outcome (modified Rankin Scale score 0-2). The primary safety end point was 90-day all-cause mortality. An imaging core lab determined modified Thrombolysis in Cerebral Infarction scores, Alberta Stroke Program Early CT Scores, clot location, and occurrence of intracranial hemorrhage at 24 hours. Independent medical reviewers adjudicated safety end points. RESULTS: Six hundred fifty patients were enrolled (median age 70 years, 54.0% female, 49.2% given intravenous recombinant tissue-type plasminogen activator before thrombectomy). Rate of modified Thrombolysis in Cerebral Infarction 2b to 3 postprocedure was 87.8% (95% CI, 85.3%-90.4%). First pass and postprocedure rates of modified Thrombolysis in Cerebral Infarction 2c to 3 were 41.5% and 66.2%, respectively. At 90 days, 55.8% (95% CI, 51.9%-59.7%) had modified Rankin Scale score 0 to 2, and all-cause mortality was 15.5% (95% CI, 12.8%-18.3%). CONCLUSIONS: Using Penumbra System for frontline mechanical thrombectomy treatment of patients with large vessel occlusion-acute ischemic stroke in a real-world setting was associated with angiographic, clinical, and safety outcomes that were comparable to prior randomized clinical trials with stringent site and operator selection criteria. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03464565.

Stenting and Angioplasty in Neurothrombectomy: Matched Analysis of Rescue Intracranial Stenting Versus Failed Thrombectomy.

BACKGROUND: Successful reperfusion is one of the strongest predictors of functional outcomes after mechanical thrombectomy (MT). Despite continuous advancements in MT technology and techniques, reperfusion failure still occurs in ≈15% to 30% of patients with large vessel occlusion strokes undergoing MT. We aim to evaluate the safety and efficacy of rescue intracranial stenting for large vessel occlusion stroke after failed MT. METHODS: The SAINT (Stenting and Angioplasty in Neurothrombectomy) Study is a retrospective analysis of prospectively collected data from 14 comprehensive stroke centers through January 2015 to December 2020. Patients were included if they had anterior circulation large vessel occlusion stroke due to intracranial internal carotid artery and middle cerebral artery-M1/M2 segments and failed MT. The cohort was divided into 2 groups: rescue intracranial stenting and failed recanalization (modified Thrombolysis in Cerebral Ischemia score 0-1). Propensity score matching was used to balance the 2 groups. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale at 90 days. Secondary outcomes included functional independence (90-day modified Rankin Scale score 0-2). Safety measures included symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: A total of 499 patients were included in the analysis. Compared with the failed reperfusion group, rescue intracranial stenting had a favorable shift in the overall modified Rankin Scale score distribution (acOR, 2.31 [95% CI, 1.61-3.32]; P<0.001), higher rates of functional independence (35.1% versus 7%; adjusted odds ratio [aOR], 6.33 [95% CI, 3.14-12.76]; P<0.001), and lower mortality (28% versus 46.5%; aOR, 0.55 [95% CI, 0.31-0.96]; P=0.04) at 90 days. Rates of symptomatic intracerebral hemorrhage were comparable across both groups (7.1% versus 10.2%; aOR, 0.99 [95% CI, 0.42-2.34]; P=0.98). The matched cohort analysis demonstrated similar results. Specifically, rescue intracranial stenting (n=107) had a favorable shift in the overall modified Rankin Scale score distribution (acOR, 3.74 [95% CI, 2.16-6.57]; P<0.001), higher rates of functional independence (34.6% versus 6.5%; aOR, 10.91 [95% CI, 4.11-28.92]; P<0.001), and lower mortality (29.9% versus 43%; aOR, 0.49 [95% CI, 0.25-0.94]; P=0.03) at 90 days with similar rates of symptomatic intracerebral hemorrhage (7.5% versus 11.2%; aOR, 0.87 [95% CI, 0.31-2.42]; P=0.79) compared with patients who failed to reperfuse (n=107). There was no heterogeneity of treatment effect across the prespecified subgroups for improvement in functional outcomes. CONCLUSIONS: Acute intracranial stenting appears to be a safe and effective rescue strategy in patients with large vessel occlusion stroke who failed MT. Randomized multicenter trials are warranted.

Reperfusion Without Functional Independence in Late Presentation of Stroke With Large Vessel Occlusion.

BACKGROUND: Reperfusion without functional independence (RFI) is an undesired outcome following thrombectomy in acute ischemic stroke. The primary objective was to evaluate, in patients presenting with proximal anterior circulation occlusion stroke in the extended time window, whether selection with computed tomography (CT) perfusion or magnetic resonance imaging is associated with RFI, mortality, or symptomatic intracranial hemorrhage (sICH) compared with noncontrast CT selected patients. METHODS: The CLEAR study (CT for Late Endovascular Reperfusion) was a multicenter, retrospective cohort study of stroke patients undergoing thrombectomy in the extended time window. Inclusion criteria for this analysis were baseline National Institutes of Health Stroke Scale score ≥6, internal carotid artery, M1 or M2 segment occlusion, prestroke modified Rankin Scale score of 0 to 2, time-last-seen-well to treatment 6 to 24 hours, and successful reperfusion (modified Thrombolysis in Cerebral Infarction 2c-3). RESULTS: Of 2304 patients in the CLEAR study, 715 patients met inclusion criteria. Of these, 364 patients (50.9%) showed RFI (ie, mRS score of 3-6 at 90 days despite successful reperfusion), 37 patients (5.2%) suffered sICH, and 127 patients (17.8%) died within 90 days. Neither imaging selection modality for thrombectomy candidacy (noncontrast CT versus CT perfusion versus magnetic resonance imaging) was associated with RFI, sICH, or mortality. Older age, higher baseline National Institutes of Health Stroke Scale, higher prestroke disability, transfer to a comprehensive stroke center, and a longer interval to puncture were associated with RFI. The presence of M2 occlusion and higher baseline Alberta Stroke Program Early CT Score were inversely associated with RFI. Hypertension was associated with sICH. CONCLUSIONS: RFI is a frequent phenomenon in the extended time window. Neither magnetic resonance imaging nor CT perfusion selection for mechanical thrombectomy was associated with RFI, sICH, and mortality compared to noncontrast CT selection alone. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04096248.

Acute ischaemic stroke associated with SARS-CoV-2 infection in North America.

BACKGROUND: To analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome. METHODS: Multicentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications. RESULTS: A total of 216 COVID-19 patients with AIS were included. 68.1% (147/216) were older than 60 years, while 31.9% (69/216) were younger. Median [IQR] National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.5 (15.8), and 44.2% (87/197) presented with large vessel occlusion (LVO). Approximately 51.3% (98/191) of the patients had poor outcomes with an observed mortality rate of 39.1% (81/207). Age >60 years (aOR: 5.11, 95% CI 2.08 to 12.56, p<0.001), diabetes mellitus (aOR: 2.66, 95% CI 1.16 to 6.09, p=0.021), higher NIHSS at admission (aOR: 1.08, 95% CI 1.02 to 1.14, p=0.006), LVO (aOR: 2.45, 95% CI 1.04 to 5.78, p=0.042), and higher NLR level (aOR: 1.06, 95% CI 1.01 to 1.11, p=0.028) were significantly associated with poor functional outcome. CONCLUSION: There is relationship between COVID-19-associated AIS and severe disability or death. We identified several factors which predict worse outcomes, and these outcomes were more frequent compared to global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-Dimer, predicted both morbidity and mortality.

Exposure to Neurointervention During Neurology Training.

There is an urgent need to include a dedicated neurointerventional rotation in the curriculum of neurology residency and vascular neurology fellowship based on the paradigm shift in recent years of stroke workflow. The recent changes coupled with growing body of evidence about lack of neurointerventional exposure in current curriculum makes it imperative for us to restructure the training for future neurologists. The exposure will prepare the neurology house-staff for the contemporary management of cerebrovascular diseases and will lead to high quality, patient-centric care.

Clinically Approximated Hypoperfused Tissue in Large Vessel Occlusion Stroke.

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.

Integrated Stroke System Model Expands Availability of Endovascular Therapy While Maintaining Quality Outcomes.

BACKGROUND AND PURPOSE: The optimal endovascular stroke therapy (EVT) care delivery structure is unknown. Here, we present our experience in creating an integrated stroke system (ISS) to expand EVT availability throughout our region while maintaining hospital and physician quality standards. METHODS: We identified all consecutive patients with large vessel occlusion acute ischemic stroke treated with EVT from January 2014 to February 2019 in our health care system. In October 2017, we implemented the ISS, in which 3 additional hospitals (4 total) became EVT-performing hospitals (EPHs) and physicians were rotated between all centers. The cohort was divided by time into pre-ISS and post-ISS, and the primary outcome was time from stroke onset to EPH arrival. Secondary outcomes included hospital and procedural quality metrics. We performed an external validation using data from the Southeast Texas Regional Advisory Council. RESULTS: Among 513 patients with large vessel occlusion acute ischemic stroke treated with EVT, 58% were treated pre-ISS and 43% post-ISS. Over the study period, EVT procedural volume increased overall but remained relatively low at the 3 new EPHs (<70 EVT/y). After ISS, the proportion of patients who underwent interhospital transfer decreased (46% versus 37%; P<0.05). In adjusted quantile regression, ISS implementation resulted in a reduction of time from stroke onset to EPH arrival by 40 minutes (P<0.01) and onset to groin puncture by 29 minutes (P<0.05). Rates of postprocedural hemorrhage, modified Thrombolysis in Cerebral Infarction (TICI) 2b/3, and 90-day modified Rankin Scale were comparable at the higher and lower volume EPHs. The improvement in onset-to-arrival time was not reflective of overall improvement in secular trends in regional prehospital care. CONCLUSIONS: In our system, increasing EVT availability decreased time from stroke onset to EPH arrival. The ISS provides a framework to maintain quality in lower volume hospitals.

Automated prediction of final infarct volume in patients with large-vessel occlusion acute ischemic stroke.

OBJECTIVE: In patients with large-vessel occlusion (LVO) acute ischemic stroke (AIS), determinations of infarct size play a key role in the identification of candidates for endovascular stroke therapy (EVT). An accurate, automated method to quantify infarct at the time of presentation using widely available imaging modalities would improve screening for EVT. Here, the authors aimed to compare the performance of three measures of infarct core at presentation, including an automated method using machine learning. METHODS: Patients with LVO AIS who underwent successful EVT at four comprehensive stroke centers were identified. Patients were included if they underwent concurrent noncontrast head CT (NCHCT), CT angiography (CTA), and CT perfusion (CTP) with Rapid imaging at the time of presentation, and MRI 24 to 48 hours after reperfusion. NCHCT scans were analyzed using the Alberta Stroke Program Early CT Score (ASPECTS) graded by neuroradiology or neurology expert readers. CTA source images were analyzed using a previously described machine learning model named DeepSymNet (DSN). Final infarct volume (FIV) was determined from diffusion-weighted MRI sequences using manual segmentation. The primary outcome was the performance of the three infarct core measurements (NCHCT-ASPECTS, CTA with DSN, and CTP-Rapid) to predict FIV, which was measured using area under the receiver operating characteristic (ROC) curve (AUC) analysis. RESULTS: Among 76 patients with LVO AIS who underwent EVT and met inclusion criteria, the median age was 67 years (IQR 54-76 years), 45% were female, and 37% were White. The median National Institutes of Health Stroke Scale score was 16 (IQR 12-22), and the median NCHCT-ASPECTS on presentation was 8 (IQR 7-8). The median time between when the patient was last known to be well and arrival was 156 minutes (IQR 73-303 minutes), and between NCHCT/CTA/CTP to groin puncture was 73 minutes (IQR 54-81 minutes). The AUC was obtained at three different cutoff points: 10 ml, 30 ml, and 50 ml FIV. At the 50-ml FIV cutoff, the AUC of ASPECTS was 0.74; of CTP core volume, 0.72; and of DSN, 0.82. Differences in AUCs for the three predictors were not significant for the three FIV cutoffs. CONCLUSIONS: In a cohort of patients with LVO AIS in whom reperfusion was achieved, determinations of infarct core at presentation by NCHCT-ASPECTS and a machine learning model analyzing CTA source images were equivalent to CTP in predicting FIV. These findings have suggested that the information to accurately predict infarct core in patients with LVO AIS was present in conventional imaging modalities (NCHCT and CTA) and accessible by machine learning methods.

Prevalence, Predictors, and Outcomes of Prolonged Mechanical Ventilation After Endovascular Stroke Therapy.

BACKGROUND: To investigate the rates, predictors, and outcomes of prolonged mechanical ventilation (≥ 96 h) following endovascular treatment (EVT) of ischemic stroke. METHODS: Hospitalizations with acute ischemic stroke and EVT were identified using validated codes in the National Inpatient Sample (2010-2015). The primary outcome was prolonged mechanical ventilation defined as ventilation ≥ 96 consecutive hours. We compared hospitalizations involving prolonged ventilation following EVT with those that did not involve prolonged ventilation. Propensity score matching was used to adjust for differences between groups. Clinical predictors of prolonged ventilation were assessed using multivariable conditional logistic regression analyses. RESULTS: Among the 34,184 hospitalizations with EVT, 5087 (14.9%) required prolonged mechanical ventilation. There was a decline in overall intubation and prolonged ventilation during the study period. On multivariable analysis, history of heart failure [OR 1.28 (95% CI 1.05-1.57)] and diabetes [OR 1.22 (95% CI 1-1.50)] was independent predictors of prolonged ventilation following EVT. In a sensitivity analysis of anterior circulation stroke only, heart failure [OR 1.3 (95% CI 1.10-1.61)], diabetes [OR 1.25 (95% CI 1.01-1.57)], and chronic lung disease [OR 1.31 (95% CI 1.03-1.66)] were independent predictors of prolonged ventilation. The weighted proportions of in-hospital mortality, post-procedural shock, acute renal failure, and intracerebral hemorrhage were higher in the prolonged ventilation group. CONCLUSIONS: Among a nationally representative sample of hospitalizations, nearly one-in-six patients had prolonged mechanical ventilation after EVT. Heart failure and diabetes were significantly associated with prolonged mechanical ventilation following EVT. Prolonged ventilation was associated with significant increase in in-hospital mortality and morbidity.

Racial and Ethnic Disparities in Functional Outcome after Thrombectomy: A Cohort Study of an Integrated Stroke Network.

OBJECTIVES: Previous studies have shown racial disparities in access to treatment and outcomes in ischemic stroke patients. We sought to define racial disparities in functional outcomes among ischemic stroke patients receiving endovascular thrombectomy (EVT). MATERIALS AND METHODS: We performed a retrospective review of patients in our institution's prospectively collected stroke patient registry from 08/2015 to 06/2019 at 1 comprehensive and 2 thrombectomy-ready stroke centers. We reviewed patients aged ≥ 18 who received mechanical thrombectomy including only patients with race/ethnicity data belonging to the 3 largest race/ethnic groups: Non-Hispanic White (NHW), Non-Hispanic Black (NHB), and Hispanic (HIS). We compared baseline characteristics and performed multivariable logistic regression to evaluate differences in good functional outcome defined as 90-day modified Rankin score (90 day mRS 0-2) as the primary outcome. Secondary outcomes were discharge disposition, length of stay, and excellent functional outcome (90 day mRS 0-1). Results are given as OR [95% CI]. RESULTS: Among 666 patients that met inclusion criteria, 45% were NHW, 30% were NHB, and 19% were HIS. NHB and HIS patients were younger than NHW (average age NHB 62; HIS 64; and NHW 70; p < 0.001). Diabetes was more prevalent in NHB (32%, p = 0.02) and HIS (47%, p < 0.001) compared to NHW (23%). There were no significant racial differences in pre-morbid mRS, arrival NIHSS, tPA treatment rates. There was no difference in primary outcome by race comparing NHW to the other racial groups (OR 1.08 [0.68-1.72]) but compared to HIS patients, NHW had a higher likelihood of the secondary outcome of excellent functional outcome (aOR 2.23 [1.01-4.93]) defined as mRS 0-1. CONCLUSIONS: In this study of over 600 patients treated with EVT, we did not find significant racial disparities in functional outcome except for less excellent functional outcome in HIS compared to NHW. Further study on disparities in post-acute stroke care is needed.