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Background: Pretreatment computed tomography perfusion parameter relative cerebral blood volume (rCBV) lesion volume has been shown to predict 90-day modified Rankin Scale score in small-core strokes with Alberta Stroke Program Early Computed Tomography Score ≥5, including those with medium-vessel occlusions (mid and distal M2 segment occlusions). Hence, in this study we aim to assess the performance of different rCBV lesion volume thresholds (rCBV <42%, rCBV <38%, and rCBV <34%) with 90-day modified Rankin Scale score including patients with large core (Alberta Stroke Program Early Computed Tomography Score <5) and strictly including only patients with anterior circulation large-vessel occlusion., Methods and Results: In this retrospective evaluation of our prospectively collected database, inclusion criteria were (1) Computed tomographic angiography confirmed anterior circulation large-vessel occlusion from September 1, 2017, to October 1, 2023; and (2) diagnostic computed tomography perfusion. Student t test, Mann-Whitney U test, and χ 2 test were used in the univariate data analysis. Spearman's rank correlation analysis was used to assess correlations. Outcome measure was dichotomized into good functional outcome (90-day modified Rankin Scale score, 0-2) and poor functional outcome (90-day modified Rankin Scale score, 3-6) for logistic regression and receiver operating characteristic analysis. P ≤0.05 was considered significant. In total, 229 patients met our inclusion criteria. The majority of the patients (n=161) in our cohort had M1 occlusion. All the rCBV thresholds were significantly higher in patients with poor 90-day functional outcomes and were independently associated with the outcome. Spearman's rank correlation analysis revealed a slightly stronger correlation of rCBV <42% (ρ=0.27, P <0.001), as compared with rCBV <38% (ρ=0.25, P <0.001) and rCBV <34% (ρ=0.24, P <0.001) with functional outcome. Receiver operating characteristic analysis revealed that rCBV <42% (area under the curve, 0.67 [95% CI, 0.60-0.74]; P <0.001) performed marginally better than rCBV <38% (area under the curve, 0.66 [95% CI, 0.59-0.73]; P <0.001), and rCBV <34% (area under the curve, 0.65 [95% CI, 0.58-0.72]; P <0.001)., Conclusions: All the rCBV thresholds were independently associated with poor 90-day functional outcome; however, the rCBV <42% marginally outperformed rCBV <38% and rCBV <34% lesion volumes.

Objectives: The variation in quality and quantity of collateral status (CS) is in part responsible for a wide variability in extent of neural damage following acute ischemic stroke from large vessel occlusion (AIS-LVO). Single-phase CTA based clot burden score (CBS) is a promising marker in estimating CS. The aim of this study is to assess the relationship of pretreatment CTA based CBS with the reference standard Digital subtraction angiography (DSA) based American Society of Interventional and Therapeutic Neuroradiology (ASITN) CS., Methods: In this retrospective study, inclusion criteria were as follows: (1) Anterior circulation LVO confirmed on CTA from January 9, 2017 to January 10, 2023; (2) diagnostic CTA; and (3) underwent mechanical thrombectomy with documented DSA CS. Spearman's rank correlation analysis, multivariate logistic regression and ROC analysis was performed to assess the correlation of CTA CBS with DSA CS. P ≤ .05 was considered significant., Results: 292 consecutive patients (median age = 68 years; 56.2% female) met our inclusion criteria. CTA CBS and DSA CS showed significant positive correlation (ρ = 0.51, P < .001). On multivariate logistic regression analysis CBS was found to be independently associated with DSA CS (adjusted OR = 1.83, P < .001, 95% CI: 1.54-2.19), after adjusting for age, sex, race, hyperlipidemia, hypertension, diabetes, prior stroke or transient ischemic attack, atrial fibrillation, premorbid mRS, admission NIH stroke scale, and ASPECTS. ROC analysis of CBS in predicting good DSA CS showed AUC of 0.76 (P < .001; 95% CI: 0.68-0.82). CBS threshold of > 6 has 84.6% sensitivity and 42.3% specificity in predicting good DSA CS., Conclusion: CTA CBS is independently associated with DSA CS and serves as a valuable supplementary tool for CS estimation. Further research is necessary to enhance our understanding of the role of CTA CBS in clinical decision-making for patients with AIS-LVO., Advances in Knowledge: CBS by indirectly estimating CS has shown to predict outcomes in AIS-LVO patients. No studies report association of CBS with reference standard DSA. In this study we further establish CBS as an independent marker of CS., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Purpose: Acute ischemic stroke due to anterior circulation large-vessel occlusion (AIS-LVO) remains a leading cause of disability despite successful reperfusion therapies. Prolonged venous transit (PVT) has emerged as a potential prognostic imaging biomarker in AIS-LVO. We aimed to investigate whether PVT is associated with a decreased likelihood of excellent functional outcome (modified Rankin Scale [mRS] score of 0-1 at 90 days) after successful reperfusion., Methods: In our prospectively collected, retrospectively reviewed database, we analyzed data from 104 patients with AIS-LVO who achieved successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2b/2c/3) between September 2017 and September 2022. PVT was defined as a time to maximum (Tmax) of ≥10 s in the superior sagittal sinus and/or torcula on computed tomography perfusion (CTP) imaging. Patients were categorized into PVT-positive (PVT+) and PVT-negative (PVT-) groups. The primary outcome was excellent functional recovery at 90 days., Results: Of the 104 patients, 30 (29%) were PVT+. Excellent functional outcome was achieved in 38 patients (37%). PVT+ patients had a significantly lower rate of excellent recovery compared to PVT- patients (11% vs. 39%; p < 0.001). After adjusting for possible confounders, PVT positivity was independently associated with lower odds of excellent recovery (adjusted odds ratio 0.11, 95% confidence interval 0.02 to 0.48; p = 0.006)., Conclusions: Among patients with AIS-LVO who achieved successful reperfusion, PVT positivity was independently associated with a decreased likelihood of excellent functional outcome at 90 days. Assessment of PVT on CTP may provide valuable prognostic information and aid in clinical decision making for patients with AIS-LVO., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Non-Hispanic Black (NHB) patients experience increased prevalence of stroke risk factors and stroke incidence compared with non-Hispanic White (NHW) patients. However, little is known about >90-day post-stroke functional outcomes following mechanical thrombectomy., Objective: To describe patient characteristics, evaluate stroke risk factors, and analyze the adjusted impact of race on long-term functional outcomes to better identify and limit sources of disparity in post-stroke care., Methods: We retrospectively reviewed 326 patients with ischemic stroke who underwent thrombectomy at two centers between 2019 and 2022. Race was self-reported as NHB, NHW, or non-Hispanic Other. Stroke risk factors, insurance status, procedural parameters, and post-stroke functional outcomes were collected. Good outcomes were defined as modified Rankin Scale score ≤2 and/or discharge disposition to home/self-care. To assess the impact of race on outcomes at 3-, 6-, and 12-months' follow-up, we performed univariate and multivariate logistic regression., Results: Patients self-identified as NHB (42%), NHW (53%), or Other (5%). 177 (54.3%) patients were female; the median (IQR) age was 67.5 (59-77) years. The median (IQR) National Institutes of Health Stroke Scale score was 15 (10-20). On univariate analysis, NHB patients were more likely to have poor short- and long-term functional outcomes, which persisted on multivariate analysis as significant at 3 and 6 months but not at 12 months (3 months: OR=2.115, P=0.04; 6 months: OR=2.423, P=0.048; 12 months: OR=2.187, P=0.15). NHB patients were also more likely to be discharged to rehabilitation or hospice/death than NHW patients after adjusting for confounders (OR=1.940, P=0.04)., Conclusions: NHB patients undergoing thrombectomy for ischemic stroke experience worse 3- and 6-month functional outcomes than NHW patients after adjusting for confounders. Interestingly, this disparity was not detected at 12 months. Future research should focus on identifying social determinants in the short-term post-stroke recovery period to improve parity in stroke care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hemorrhagic conversion (HC) is a known complication after acute ischemic stroke (AIS) in patients undergoing mechanical thrombectomy (MT). Although symptomatic HC has been shown to lead to poor neurologic outcomes, the effect of asymptomatic HC (aHC) is unclear. This study aims to identify predictors of aHC and to determine the short-term outcomes., Methods: This is a single-institution retrospective study of patients with anterior circulation stroke (AIS) who underwent MT between January 2016 and September 2022. Radiographic HC was identified on postoperative imaging. Asymptomatic hemorrhage was defined as no acute neurologic decline attributable to imaging findings. Baseline characteristics, technical aspects, and outcomes were compared between aHC and no-HC groups. Logistic regression and multivariate analysis were performed., Results: A total of 615 patients underwent MT for AIS, of whom 496 met the inclusion criteria. A total of 235 patients (47.4%) had evidence of aHC. Diabetes mellitus (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.06-2.41; P = 0.03), hyperglycemia (OR, 1.01; 95% CI, 1.00-1.01; P = 0.002), greater number of passes (OR, 1.14; 95% CI, 1.00-1.31; P = 0.05), and longer time to reperfusion (OR, 1.02; 95% CI, 1.00-1.05; P = 0.05) were associated with aHC. Patients with aHC were significantly more likely to require rehabilitation, whereas those without HC were more likely to be discharged home (P < 0.001). There were no significant differences in long-term outcomes., Conclusions: HC occurred in up to half of patients who underwent MT for AIS, most of whom were clinically asymptomatic. Despite clinical stability, aHC was significantly associated with a greater need for inpatient rehabilitation. Predictors of aHC included hyperglycemia and a longer time to reperfusion., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Although pretreatment radiographic biomarkers are well established for hemorrhagic transformation (HT) following successful mechanical thrombectomy (MT) in large vessel occlusion (LVO) strokes, they are yet to be explored for medium vessel occlusion (MeVO) acute ischemic strokes. We aim to investigate pretreatment imaging biomarkers representative of collateral status, namely the hypoperfusion intensity ratio (HIR) and cerebral blood volume (CBV) index, and their association with HT in successfully recanalized MeVOs. A prospectively collected registry of acute ischemic stroke patients with MeVOs successfully recanalized with MT between 2019 and 2023 was retrospectively reviewed. A multivariate logistic regression for HT of any subtype was derived by combining significant univariate predictors into a forward stepwise regression with minimization of Akaike information criterion. Of 60 MeVO patients successfully recanalized with MT, HT occurred in 28.3% of patients. Independent factors for HT included: diabetes mellitus history (p = 0.0005), CBV index (p = 0.0071), and proximal versus distal occlusion location (p = 0.0062). A multivariate model with these factors had strong diagnostic performance for predicting HT (area under curve [AUC] 0.93, p < 0.001). Lower CBV indexes, distal occlusion location, and diabetes history are significantly associated with HT in MeVOs successfully recanalized with MT. Of note, HIR was not found to be significantly associated with HT., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Acute cerebral ischemia triggers a profound inflammatory response. While macrophages polarized to an M2-like phenotype clear debris and facilitate tissue repair, aberrant or prolonged macrophage activation is counterproductive to recovery. The inhibitory immune checkpoint Programmed Cell Death Protein 1 (PD-1) is upregulated on macrophage precursors (monocytes) in the blood after acute cerebrovascular injury. To investigate the therapeutic potential of PD-1 activation, we immunophenotyped circulating monocytes from patients and found that PD-1 expression was upregulated in the acute period after stroke. Murine studies using a temporary middle cerebral artery (MCA) occlusion (MCAO) model showed that intraperitoneal administration of soluble Programmed Death Ligand-1 (sPD-L1) significantly decreased brain edema and improved overall survival. Mice receiving sPD-L1 also had higher performance scores short-term, and more closely resembled sham animals on assessments of long-term functional recovery. These clinical and radiographic benefits were abrogated in global and myeloid-specific PD-1 knockout animals, confirming PD-1+ monocytes as the therapeutic target of sPD-L1. Single-cell RNA sequencing revealed that treatment skewed monocyte maturation to a non-classical Ly6C lo , CD43 hi , PD-L1+ phenotype. These data support peripheral activation of PD-1 on inflammatory monocytes as a therapeutic strategy to treat neuroinflammation after acute ischemic stroke., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HB has received research funding from the National Institutes of Health, Khatib Foundation, NICO Myriad Corporation, and philanthropy. He is the Chairman of the Medical Advisory Board for Insightec, which is developing focused ultrasound treatments for brain tumors. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict-of-interest policies. He has consultation agreements with Accelerating Combination Therapies, Insightec, Candel Therapeutics, Inc., Catalio Nexus Fund II, LLC, LikeMinds, Inc*, Galen Robotics, Inc.*, CraniUS*, and Nurami Medical* (Includes equity or options). ML has received research funding from Arbor, Bristol Myers Squibb, Accuray, Biohaven, and Urogen. He is a consultant for VBI, InCephalo Therapeutics, Merck, Pyramid Bio, Insightec, Biohaven. Sanianoia, Novocure, Noxxon, Hemispherian, InCando, Century Therapeutics, CraniUs, MediFlix, and XSense. He is a shareholder in Egret Therapeutics. He is an inventor on patents for focused radiation + checkpoint inhibitors, local chemotherapy + checkpoint inhibitors, and checkpoints and Neuro-inflammation. He is a non-research consultant for Stryker and on the DSMB for Cellularity. RJT is an inventor on patents for immune checkpoints and neuroinflammation. CMJ has received research support from Biohaven, InCephalo, the Goldhirsh-Yellin Foundation, the Brain Aneurysm Foundation, and philanthropy. He is an inventor on patents for immune checkpoints and neuroinflammation. He is the co-founder and owns equity interest in Egret Therapeutics. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict-of-interest policies., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Acute ischemic stroke (AIS) is the second leading cause of death globally. Mechanical thrombectomy (MT) has improved patient prognosis but expedient treatment is still necessary to minimize anoxic injury. Lower intraoperative body temperature decreases cerebral oxygen demand, but the role of hypothermia in treatment of AIS with MT is unclear., Methods: We retrospectively reviewed patients undergoing MT for AIS from 2014 to 2020 at our institution. Patient demographics, comorbidities, intraoperative parameters, and outcomes were collected. Maximum body temperature was extracted from minute-by-minute anesthesia readings, and patients with maximal temperature below 36°C were considered hypothermic. Risk factors were assessed by χ 2 and multivariate ordinal regression., Results: Of 68 patients, 27 (40%) were hypothermic. There was no significant association of hypothermia with patient age, comorbidities, time since last known well, number of passes intraoperatively, favorable revascularization, tissue plasminogen activator use, and immediate postoperative complications. Hypothermic patients exhibited better neurologic outcome at 3-month follow-up (P = 0.02). On multivariate ordinal regression, lower maximum intraoperative body temperature was associated with improved 3-month outcomes (P < 0.001), when adjusting for other factors influencing neurological outcomes. Other significant protective factors included younger age (P = 0.03), better revascularization (P = 0.03), and conscious sedation (P = 0.02)., Conclusions: Lower intraoperative body temperature during MT was independently associated with improved neurological outcome in this single center retrospective series. These results may help guide clinicians in employing therapeutic hypothermia during MT to improve long-term neurologic outcomes from AIS, although larger studies are needed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: For patients presenting with acute ischemic stroke (AIS) caused by large vessel occlusions (LVO), mechanical thrombectomy (MT) is the treatment standard of care in eligible patients. Modified Thrombolysis in Cerebral Infarction (mTICI) grades of 2b, 2c, and 3 are all considered successful reperfusion; however, recent studies have shown achieving mTICI 2c/3 leads to better outcomes than mTICI 2b. This study aims to investigate whether any baseline preprocedural or periprocedural parameters are predictive of achieving mTICI 2c/3 in successfully recanalized LVO patients., Methods: We conducted a retrospective multicenter cohort study of consecutive patients presenting with AIS caused by a LVO from 1 January 2017 to 1 January 2023. Baseline and procedural data were collected through chart review. Univariate and multivariate analysis were applied to determine significant predictors of mTICI 2c/3., Results: A total of 216 patients were included in the study, with 159 (73.6%) achieving mTICI 2c/3 recanalization and 57 (26.4%) achieving mTICI 2b recanalization. We found that a higher groin puncture to first pass time (OR = 0.976, 95%CI: 0.960-0.992, p = 0.004), a higher first pass to recanalization time (OR = 0.985, 95%CI: 0.972-0.998, p = 0.029), a higher admission NIHSS (OR = 0.949, 95%CI: 0.904-0.995, p = 0.031), and a lower age (OR = 1.032, 95%CI: 1.01-1.055, p = 0.005) were associated with a decreased probability of achieving mTICI 2c/3., Interpretation: A lower groin puncture to first pass time, a lower first pass to recanalization time, a lower admission NIHSS, and a higher age were independent predictors of mTICI 2c/3 recanalization., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background and Purpose: Acute ischemic stroke due to large vessel occlusion (AIS-LVO) is a major cause of functional dependence. Collateral status (CS) is an important determinant of functional outcomes. Pretreatment CT perfusion (CTP) parameters serve as reliable surrogates of CS. Penumbra Salvage Index (PSI) is another parameter predictive of functional outcomes in AIS-LVO. The aim of this study is to assess the relationship of pretreatment CTP parameters with PSI., Methods: In this prospectively collected, retrospectively reviewed multicenter analysis, inclusion criteria were as follows: (1) CT angiography confirmed middle cerebral artery (MCA) M1-segment and proximal M2-segment occlusion from 9/1/2017 to 9/22/2022; (2) diagnostic CTP; and (3) available diagnostic Magnetic resonance Imaging (MRI) diffusion-weighted images. Pearson correlation analysis was performed to assess the association between cerebral blood volume (CBV) index and hypoperfusion intensity ratio (HIR) with PSI. p value ≤.05 was considered statistically significant., Results: In total, 131 patients (n = 86, M1 and n = 45, proximal M2 occlusion) met our inclusion criteria. CBV index showed a modest positive correlation with PSI (r = 0.34, p<.001) in patients with proximal MCA occlusion. Similar trends were noted in subgroup analysis of patients with M1 occlusion, and proximal M2 occlusion. Whereas, HIR did not have a strong trend or correlation with PSI., Conclusion: CBV index correlates with PSI, whereas HIR does not. Future studies are needed to expand our understanding of the adjunct role of CBV index with other similar pretreatment CTP-based markers in clinical evaluation and decision-making in patients with MCA occlusion., (© 2023 American Society of Neuroimaging.)

Objectives: Surgical revascularization for moyamoya arteriopathy decreases long-term stroke risk but carries a risk of perioperative ischemic complications. We aimed to evaluate modifiable stroke risk factors in children undergoing surgical revascularization for moyamoya., Materials and Methods: In this exploratory, single-center, retrospective cohort study, medical records of pediatric patients undergoing surgical revascularization for moyamoya arteriopathy at our center between 2003 and 2021 were reviewed. Candidate modifiable risk factors were analyzed for association with perioperative stroke, defined as ischemic stroke ≤7 days after surgery., Results: We analyzed 53 surgeries, consisting of 39 individual patients undergoing indirect surgical revascularization of 74 hemispheres. Perioperative ischemic stroke occurred following five surgeries (9.4%). There were no instances of hemorrhagic stroke. Larger pre-to-postoperative decreases in hemoglobin (OR 3.90, p=0.017), hematocrit (OR 1.69, p=0.012) and blood urea nitrogen (OR 1.83, p=0.010) were associated with increased risk of perioperative ischemic stroke. Weight-adjusted intraoperative blood loss was not associated with risk of perioperative ischemic stroke (OR 0.94, p=0.796). Among children with sickle cell disease, all of whom underwent exchange transfusion within one week prior to surgery, none experienced perioperative stroke., Conclusions: Decreases in hemoglobin, hematocrit, and blood urea nitrogen between the preoperative and postoperative periods are associated with increased risk of perioperative stroke. These novel findings suggest that dilutional anemia, possibly due to standardly administered hyperhydration, may increase the risk of perioperative stroke in some children with moyamoya. Further work optimizing both mean arterial pressure and oxygen-carrying capacity in these patients, including consideration of alternative blood transfusion thresholds, is necessary., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Background and Purpose: Quantitative CT perfusion (CTP) thresholds for assessing the extent of ischemia in patients with acute ischemic stroke (AIS) have been established; relative cerebral blood flow (rCBF) <30% is typically used for estimating estimated ischemic core volume and T max (time to maximum) >6 seconds for critical hypoperfused volume in AIS patients with large vessel occlusion (LVO). In this study, we aimed to identify the optimal threshold values for patients presenting with AIS secondary to distal medium vessel occlusions (DMVOs)., Methods: In this retrospective study, consecutive AIS patients with anterior circulation DMVO who underwent pretreatment CTP and follow-up MRI/CT were included. The CTP data were processed by RAPID (iSchemaView, Menlo Park, CA) to generate estimated ischemic core volumes using rCBF <20%, <30%, <34%, and <38% and critical hypoperfused volumes using T max (seconds) >4, >6, >8, and >10. Final infarct volumes (FIVs) were obtained from follow-up MRI/CT within 5 days of symptom onset. Diagnostic performance between CTP thresholds and FIV was assessed in the successfully and unsuccessfully recanalized groups., Results: Fifty-five patients met our inclusion criteria (32 female [58.2%], 68.0 ± 12.1 years old [mean ± SD]). Recanalization was attempted with intravenous tissue-type plasminogen activator and mechanical thrombectomy in 27.7% and 38.1% of patients, respectively. Twenty-five patients (45.4%) were successfully recanalized. In the successfully recanalized patients, no CTP threshold significantly outperformed what is used in LVO setting (rCBF < 30%). All rCBF CTP thresholds demonstrated fair diagnostic performances for predicting FIV. In unsuccessfully recanalized patients, all T max CTP thresholds strongly predicted FIV with relative superiority of T max >10 seconds (area under the receiver operating characteristic curve = .875, p = .001)., Conclusion: In AIS patients with DMVOs, longer T max delays than T max  > 6 seconds, most notably, T max  > 10 seconds, best predict FIV in unsuccessfully recanalized patients. No CTP threshold reliably predicts FIV in the successfully recanalized group nor significantly outperformed rCBF < 30%., (© 2023 American Society of Neuroimaging.)

Objective: Patients with nmoyamoya disease (MMD) who present primarily with ischemic stroke are known to have greater rates of perioperative strokes as compared with those who present with nonstroke symptoms. The optimal timing for revascularization for these patients remains unclear., Methods: From 1994 to 2015, 91 patients with MMD presented with signs and symptoms of an acute ischemic stroke with diffusion restriction correlate on magnetic resonance imaging, and these patients were subdivided into those who underwent early revascularization (<90 days from last stroke), versus those who underwent delayed revascularization (≥90 days after last stroke), based on evidence that most neurological recovery after stroke occurs during the first three months. Perioperative and long-term outcomes were compared between the 2 surgical cohorts., Results: In total, 27 patients underwent early revascularization, and 64 patients underwent delayed revascularization. Patients who underwent early revascularization had a statistically greater rate of perioperative stroke (P = 0.04) and perioperative mortality (P = 0.03), and overall complication rate (P = 0.049). At last follow-up of 5.2 ± 4.3 years, patients who underwent delayed revascularization had a lower mortality rate (P = 0.01) and a lower overall postoperative stroke incidence (P = 0.002). As a function of time, patients with MMD undergoing delayed revascularization had a statistically higher length of stroke-free survival (P = 0.005)., Conclusions: Patients with MMD who present with ischemic stroke are more likely to have perioperative strokes, overall perioperative complications, worse long-term mortality rates, and lower rates of stroke-free survival if revascularization surgery occurred within 90 days of last stroke., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The immune response to ischemic stroke is an area of study that is at the forefront of stroke research and presents promising new avenues for treatment development. Upon cerebral vessel occlusion, the innate immune system is activated by danger-associated molecular signals from stressed and dying neurons. Microglia, an immune cell population within the central nervous system which phagocytose cell debris and modulate the immune response via cytokine signaling, are the first cell population to become activated. Soon after, monocytes arrive from the peripheral immune system, differentiate into macrophages, and further aid in the immune response. Upon activation, both microglia and monocyte-derived macrophages are capable of polarizing into phenotypes which can either promote or attenuate the inflammatory response. Phenotypes which promote the inflammatory response are hypothesized to increase neuronal damage and impair recovery of neuronal function during the later phases of ischemic stroke. Therefore, modulating neuroimmune cells to adopt an anti-inflammatory response post ischemic stroke is an area of current research interest and potential treatment development. In this review, we outline the biology of microglia and monocyte-derived macrophages, further explain their roles in the acute, subacute, and chronic stages of ischemic stroke, and highlight current treatment development efforts which target these cells in the context of ischemic stroke., Competing Interests: CJ is a scientific co-founder of Egret Therapeutics with equity interests in the company and inventor on a patent filed by Johns Hopkins for using PD-1 agonists to treat cerebral vasospasm and ischemia. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wicks, Ran, Kim, Xu, Lee and Jackson.)

IntroductionInternal carotid artery termination (ICAT) and proximal A1 aneurysms can be challenging for open surgical clipping or endovascular coiling. Treatment with flow diversion covering the middle cerebral artery (MCA), an end vessel supplying a terminal circulation, has not been reported.MethodsA prospective, Institutional Review Board-approved database was analysed for patients with pipeline embolisation device (PED) placement from the anterior cerebral artery (ACA) to the ICA during cerebral aneurysm treatment.ResultsNine cases were identified, including five proximal A1, three posterior communicating artery and one ICAT aneurysm locations. Average aneurysm size was 8.3 mm (range 3-17), with 67% saccular and 78% right-sided. Primary indication for treatment was significant dome irregularity (44%), recurrence or enlargement (33%), underlying collagen vascular disorder (11%) and traumatic pseudoaneurysm (11%). Preservation of the ipsilateral ACA (with PED placed in A1) was performed when the anterior communicating artery (67%) or contralateral A1 (33%) were absent on angiography. Adjunctive coiling was done in four cases (44%). There was one major stroke leading to mortality (11%) and one minor stroke (11%). Clinical follow-up was 27 months on average. Follow-up digital subtraction angiography (average interval 15 months) showed complete aneurysm obliteration (88%) or dome occlusion with entry remnant (12%). The jailed MCA showed minimal or mild delay (primarily anterograde flow) in 75% of cases and significant delay (reliance primarily on ACA and external carotid artery collaterals) in 25%.ConclusionsCovering the MCA with a flow diverting stent should be reserved for select rare cases. Strict attention to blood pressure augmentation during the periprocedural period is necessary to minimise potential ischaemic compromise.

Background and Purpose: In large vessel occlusion (LVO) stroke patients, relative cerebral blood flow (rCBF)<30% volume thresholds are commonly used in treatment decisions. In the early time window, nearly infarcted but salvageable tissue volumes may lead to pretreatment overestimates of infarct volume, and thus potentially exclude patients who may otherwise benefit from intervention. Our multisite analysis aims to explore the strength of relationships between widely used pretreatment CT parameters and clinical outcomes for early window stroke patients. Methods: Patients from two sites in a prospective registry were analyzed. Patients with LVOs, presenting within 3 hours of last known well, and who were successfully reperfused were included. Primary short‐term neurological outcome was percent National Institutes of Health Stroke Scale (NIHSS) change from admission to discharge. Secondary long‐term outcome was 90‐day modified Rankin score. Spearman's correlations were performed. Significance was attributed to p‐value ≤.05. Results: Among 73 patients, median age was 66 (interquartile range 54‐76) years. Among all pretreatment imaging parameters, rCBF<30%, rCBF<34%, and rCBF<38% volumes were significantly, inversely correlated with percentage NIHSS change (p<.048). No other parameters significantly correlated with outcomes. Conclusions: Our multisite analysis shows that favorable short‐term neurological recovery was significantly correlated with rCBF volumes in the early time window. However, modest strength of correlations provides supportive evidence that the applicability of general ischemic core estimate thresholds in this subpopulation is limited. Our results support future larger‐scale efforts to liberalize or reevaluate current rCBF parameter thresholds guiding treatment decisions for early time window stroke patients. [ABSTRACT FROM AUTHOR]

Randomized controlled trials comparing endovascular thrombectomy (EVT) versus EVT preceded by intravenous thrombolysis (EVT + IVT) for acute ischemic stroke due to large artery occlusion remain controversial. This systematic review and meta-analysis seek to compare these 2 modalities. Online Protocol is available at PROSPERO (york.ac.uk) (registration# CRD42022357506). MEDLINE, PubMed, and Embase were searched. The primary outcome was 90-day modified Rankin scale (mRS) ≤2. Secondary outcomes were 90-day mRS ≤1, 90-day mean mRS, National Institutes of Health Stroke Scale (NIHSS) at 1–3 and 3–7 days, 90-day Barthel Index, 90-day EQ-5D-5L (EuroQoL Group 5-Dimension 5-Level), the volume of infarction (mL), successful reperfusion, complete reperfusion, recanalization, 90-day mortality, any intracranial hemorrhage (ICH), symptomatic ICH, embolization in new territory, new infarction, puncture site complications, vessel dissection, and contrast extravasation. The certainty in the evidence was determined by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Six randomized controlled trials yielding 2332 patients were included, of which 1163 and 1169 underwent EVT and EVT + IVT, respectively. The relative risk (RR) of 90-day mRS ≤2 was similar between the groups (RR = 0.96[0.88, 1.04]; P = 0.28). EVT was non-inferior to EVT + IVT because the lower bond of 95% confidence interval of the risk difference (RD = −0.02 [−0.06, 0.02]; P = 0.36) exceeded the −0.1 non-inferiority margin. The certainty in the evidence was high. The RR of successful reperfusion (RR = 0.96 [0.93, 0.99]; P = 0.006), any ICH (RR = 0.87 [0.77, 0.98]; P = 0.02), and puncture site complications (RR = 0.47 [0.25, 0.88]; P = 0.02) were lower with EVT. For EVT + IVT, the number needed to treat for successful reperfusion was 25, and the number needed to harm for any ICH was 20. The 2 groups were similar in other outcomes. EVT is non-inferior to EVT + IVT. In centers capable of both EVT and IVT, if timely EVT is feasible, it is reasonable to skip bridging IVT and keep rescue thrombolysis at the discretion of the interventionist for patients presenting within 4.5 hours of anterior ischemic stroke. [ABSTRACT FROM AUTHOR]