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Objective: Despite successful endovascular therapy, a proportion of stroke patients exhibit long‐term functional decline, regardless of the cortical reperfusion. Our objective was to evaluate the early activation of the adaptive immune response and its impact on neurological recovery in patients with large vessel occlusion (LVO). Methods: Nineteen (13 females, 6 males) patients with acute LVO were enrolled in a single‐arm prospective cohort study. During endovascular therapy (EVT), blood samples were collected from pre and post‐occlusion, distal femoral artery, and median cubital vein (controls). Cytokines, chemokines, cellular and functional profiles were evaluated with immediate and follow‐up clinical and radiographic parameters, including cognitive performance and functional recovery. Results: In the hyperacute phase (within hours), adaptive immune activation was observed in the post‐occlusion intra‐arterial environment (post). Ischemic vascular tissue had a significant increase in T‐cell‐related cytokines, including IFN‐γ and MMP‐9, while GM‐CSF, IL‐17, TNF‐α, IL‐6, MIP‐1a, and MIP‐1b were decreased. Cellularity analysis revealed an increase in inflammatory IL‐17+ and GM‐CSF+ helper T‐cells, while natural killer (NK), monocytes and B‐cells were decreased. A correlation was observed between hypoperfused tissue, infarct volume, inflammatory helper, and cytotoxic T‐cells. Moreover, helper and cytotoxic T‐cells were also significantly increased in patients with improved motor function at 3 months. Interpretation: We provide evidence of the activation of the inflammatory adaptive immune response during the hyperacute phase and the association of pro‐inflammatory cytokines with greater ischemic tissue and worsening recovery after successful reperfusion. Further characterization of these immune pathways is warranted to test selective immunomodulators during the early stages of stroke rehabilitation. [ABSTRACT FROM AUTHOR]

Background and Purpose: The availability of cone‐beam CT perfusion (CBCTP) in angiography suites may improve large‐vessel occlusion (LVO) triage and reduce reperfusion times for patients presenting during extended time window. We aim to evaluate the perfusion maps correlation and agreement between multidetector CT perfusion (MDCTP) and CBCTP when obtained sequentially in patients undergoing endovascular therapy. Methods: This is a prospective, pilot, single‐arm interventional cohort study of consecutive patients with anterior circulation LVO. All patients underwent MDCTP and CBCTP prior to endovascular therapy, generating cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time‐to‐maximum/time to peak contrast concentration maps. We compared the two imaging modalities using three different methods: (1) six regions of interest (ROIs) placed in the anterior circulation territory; (2) ROIs placed in all 10 Alberta Stroke Program Early CT Score regions; and (3) ROI drawn around the entire ischemic area. ROI ratios (unaffected/affected area) were compared for all sequences in each method. We used the intraclass correlation coefficient to calculate the correlation between the studies. Bland‐Altman plots were also created to measure the degree of agreement. Finally, a sensitivity analysis was done comparing both modalities in patients with low infarct growth rate. Results: Fourteen patients were included (median age 81 years [74‐87], 50% males, median National Institutes of Health Stroke Scale 19 [14‐22]). Median time between studies was 42 minutes (interquartile range 29‐61). Independently of the method used, we found moderate to excellent correlation in CBF, CBV, and MTT between modalities. CBF correlation further improved in patients with low infarct growth. Conclusion: These results demonstrate promising accuracy of CBCTP in evaluating ischemic tissue in patients presenting with LVO ischemic stroke. [ABSTRACT FROM AUTHOR]

Objective: Cerebral amyloid angiopathy (CAA) can present with intracerebral hemorrhage (ICH), convexity subarachnoid hemorrhage (SAH), and rarely acute ischemic stroke (AIS). The objective of our study was to compare the readmission rates for recurrent ICH, SAH, and AIS among patients admitted for ICH with and without CAA. Methods: Using the National Readmissions Database 2016–2018 we identified patients admitted for ICH with and without a concomitant diagnosis of CAA. Primary outcome of the study was readmission due to ICH. Secondary outcomes included readmissions due to AIS and SAH. Survival analysis was performed, and Kaplan–Meier curves were created to assess for readmissions. Results: The study consisted of 194,290 patients with ICH, 8247 with CAA and 186,043 without CAA as a concomitant diagnosis. After propensity matching, we identified 7857 hospitalizations with CAA and 7874 without CAA. Patients with CAA had higher risk of readmission due to ICH as compared to those without CAA [hazards ratio (HR) 3.44, 95% confidence interval (CI) 2.55–4.64, P < 0.001] during the mean follow-up period of 181.4 (SD ± 106.4) days. Patients with CAA were also more likely to be readmitted due to SAH (HR 2.52, 95% CI 1.18–5.37, P 0.017) but not due to AIS (HR 0.74, 95% CI 0.54–1.01, P 0.061). Age (HR 0.96 per year increase in age, 95% CI 0.94–0.98, P < 0.001) and Medicare payer (HR 3.31; 95% CI 1.89–5.78, P < 0.001) were independently associated with readmissions due to ICH. Discussion: Patients admitted for ICH with a concomitant diagnosis of CAA are three times more likely to have readmissions for recurrent ICH compared to patients without CAA. [ABSTRACT FROM AUTHOR]

Summary: Fusarium graminearum is the primary cause of Fusarium head blight (FHB), one of the most economically important diseases of wheat worldwide. FHB reduces yield and contaminates grain with the trichothecene mycotoxin deoxynivalenol (DON), which poses a risk to plant, human and animal health. The first committed step in trichothecene biosynthesis is formation of trichodiene (TD). The volatile nature of TD suggests that it could be a useful intra or interspecies signalling molecule, but little is known about the potential signalling role of TD during F. graminearum‐wheat interactions. Previous work using a transgenic Trichoderma harzianum strain engineered to emit TD (Th + TRI5) indicated that TD can function as a signal that can modulate pathogen virulence and host plant resistance. Herein, we demonstrate that Th + TRI5 has enhanced biocontrol activity against F. graminearum and reduced DON contamination by 66% and 70% in a moderately resistant and a susceptible cultivar, respectively. While Th + TRI5 volatiles significantly influenced the expression of the pathogenesis‐related 1 (PR1) gene, the effect was dependent on cultivar. Th + TRI5 volatiles strongly reduced DON production in F. graminearum plate cultures and downregulated the expression of TRI genes. Finally, we confirm that TD fumigation reduced DON accumulation in a detached wheat head assay. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to provide a comprehensive review encompassing the syndromes associated with the lower cranial nerves (LCNs). We will discuss the anatomy of some of these syndromes and the historical contributors after whom they were named. The LCNs can be affected individually or in combination, since the cranial nerves at this level share their courses through the jugular foramen and hypoglossal canal and the extracranial spaces. Numerous alterations affecting them have been described in the literature, but much remains to be discovered on this topic. This paper will highlight some of the subtle differences among these syndromes. Symptoms and signs that have localization value for LCN lesions include impaired speech, deglutition, sensory functions, alterations in taste, autonomic dysfunction, neuralgic pain, dysphagia, head or neck pain, cardiac or gastrointestinal compromise, and weakness of the tongue, trapezius, or sternocleidomastoid muscles. To assess the manifestations of LCN lesions correctly, precise knowledge of the anatomy and physiology of the area is required. Treatments currently used for these conditions will also be addressed here. Effective treatments are available in several such cases, but a precondition for complete recovery is a correct and swift diagnosis. [ABSTRACT FROM AUTHOR]

The pharyngeal plexus is an essential anatomical structure, but the contributions from the glossopharyngeal and vagus nerves and the superior cervical ganglion that give rise to the pharyngeal plexus are not fully understood. The pharyngeal plexus is likely to be encountered during various anterior cervical surgical procedures of the neck such as anterior cervical discectomy and fusion. Therefore, a detailed understanding of its anatomy is essential for the surgeon who operates in and around this region. Although the pharyngeal plexus is an anatomical structure that is widely mentioned in literature and anatomy books, detailed descriptions of its structural nuances are scarce; therefore, we provide a comprehensive review that encompasses all the available data from this critical structure. We conducted a narrative review of the current literature using databases like PubMed, Embase, Ovid, and Cochrane. Information was gathered regarding the pharyngeal plexus to improve our understanding of its anatomy to elucidate its involvement in postoperative spine surgery complications such as dysphagia. The neural contributions of the cranial nerves IX, X, and superior sympathetic ganglion intertwine to form the pharyngeal plexus that can be injured during ACDF procedures. Factors like surgical retraction time, postoperative hematoma, surgical hardware materials, and profiles and smoking are related to postoperative dysphagia onset. Thorough anatomical knowledge and lateral approaches to ACDF are the best preventing measures. [ABSTRACT FROM AUTHOR]

An adult male was found to have a variation of the left basal vein of Rosenthal after presenting with complaints of headache and balance issues. In this case, the vein drained directly into the left superior petrosal sinus (SPS) instead of the great vein of Galen. Anatomical variation of the basal vein is likely due to embryonic development of the deep cerebral venous system as primitive structures either differentiate regress or further with age. These changes may result in the uncommon presentation seen in this case. To our knowledge, this is the first case that shows the basal vein drains into the SPS. The normal and variant anatomy of this vessel are discussed. [ABSTRACT FROM AUTHOR]

The C1 spinal nerve is a fascinating anatomic structure owing to its wide range of variations. Throughout history, understanding of the cranial and spinal nerves has probably influenced the current conception of this nerve among anatomists. Located at the craniocervical junction, the C1 spinal nerve contributes to the motor innervation of deep cervical muscles through the cervical (anterior) and Cruveilhier's (posterior) plexuses. Sensory functions of this nerve are more enigmatic; despite investigations into its dorsal rootlets, a dorsal root ganglion, and the relationships between this nerve and adjacent cranial and spinal nerves, there is still no consensus regarding its true anatomy. In this article, we review the available literature and discuss some of the developmental models that could potentially explain the wide range of variations and functions of the C1 nerve. [ABSTRACT FROM AUTHOR]

Unfavorable anatomy can preclude traditional anterograde endovascular interventions. Transcirculation approaches, which consist of primary catheterization of a target artery from the contralateral side or opposite cerebral circulation, can provide alternative pathways for successful treatment of these patients. We aimed to assess the safety, efficacy, and outcomes of endovascular embolization through transcirculation approaches. Nine centers provided retrospective data on patients who underwent transcirculation procedures for embolization of intracranial aneurysms (IAs), dural arteriovenous fistulas (dAVFs), and arteriovenous malformations (AVMs). Raymond-Roy Occlusion Classification (RROC) grades and degree of obliteration were used to evaluate treatment success. Minor/major complications and clinical/angiographic outcomes were also assessed. A review of the literature reporting patients who underwent transcirculation embolizations was also performed. Forty patients were included in the study (34 IAs, 3 AVMs, and 3 dAVFs). Most IAs (22/34, 64.7%) were treated electively. Three AVMs and 2 dAVFs presented ruptured. RROC grade I–II was achieved in 97% of IAs. All AVMs and dAVFs were completely obliterated. One patient developed a transient arterial thrombus that was successfully treated with intravenous tirofiban. The most common indications for a transcirculation approach were difficult access angle of the target lesion (42.5%) and occlusion of the parent artery (27.5%). The review of the literature pooled 152 IAs treated via transcirculation approaches. Most common locations were the basilar tip (27%), posterior inferior cerebellar artery (25%), and internal carotid artery (15.1%). The posterior communicating artery was crossed in 60 (39.5%), anterior communicating artery in 48 (31.6%), and vertebral artery in 37 (24.3%) patients. Primary coiling alone was performed in 22 (14.5%), stent-assisted coiling in 67 (44.1%), balloon-assisted coiling in 36 (23.7%), stent-assisted coiling + balloon-assisted coiling in 20 (13.2%) and flow diversion in 7 (4.6%) patients. After intervention, 142 (93.4%) IAs achieved successful RROC grades I–II. Two major complications (1.3%) leading to death were reported, both of which were intraprocedural aneurysmal ruptures with massive subarachnoid hemorrhage and herniation. After a mean angiographic follow-up of 11.3 months, only 6/108 (5.6%) IAs showed intrasaccular filling/recurrence. Transcirculation approaches seem to be safe and effective in the treatment of IAs, dAVFs, and AVMs. The most common indication for a transcirculation approach is the presence of a difficult angle to access the target lesion and occlusion of the parent artery. [ABSTRACT FROM AUTHOR]

Amidst public calls for greater internationalization, universities are marketing to international students. We explore how universities in regional hubs (Lee & Schoole, 2015) enact "dramaturgical performances" (Goffman, 1959), presenting images of themselves in geopolitical space. We find: (1) bifurcated marketing strategies to distinct student audiences; (2) differences between public and private universities in featuring lifestyle or academic issues, and higher education as a private or a public good, as in "academic capitalism" (Slaughter & Rhoades, 2004); & (3) distinctive positioning of universities by type and region in their local/national/regional space, highlighting the possibility of alternatives to dominant Anglo-American internationalization models. [ABSTRACT FROM AUTHOR]

Background: Dynamic cerebral autoregulation (DCA) is the continuous counterregulation of cerebral blood flow to fluctuations in blood pressure. DCA can become impaired after acute stroke, but it remains unclear to what extent and over what interval this occurs. Methods: We included 28 patients (NIHSS = 12 ± 6.5, age = 68.4 ± 17.1, 16F) with acute large-vessel ischemic stroke in the middle cerebral artery territory and 29 healthy controls (mean age 54.9 ± 9, 16F). DCA was assessed by simultaneous measurement of blood pressure together with blood flow velocities using finger plethysmography/arterial catheter and transcranial Doppler over three 10-minute recordings on days 0-2, 3-6 and ≥7 days after stroke. Transfer function analysis was applied to calculate average phase shift (PS) in the low frequency range (0.06-0.12 Hz). Less PS indicated poorer autoregulation. The affected side was compared with the unaffected side and controls. Univariate comparisons of data were performed using t tests at single time points, and generalized estimating equations with an exchangeable correlation matrix to examine the change in PS over time. Results: At mean 1.3 ± 0.5 days after stroke the average PS in the affected hemisphere was 29.6 ± 10.5 vs. 42.5 ± 13 degrees in the unaffected hemisphere (p = 0.004). At 4.1 ± 1 days, the PS in affected and unaffected hemisphere was 23.2 ± 19.1 vs. 41.7 ± 18.5 degrees, respectively (p = 0.003). At mean 9.75 ± 2.2 days stroke there was no difference between the affected and the unaffected hemisphere (53.2 ± 28.2 vs. 50.7 ± 29.2 degrees, p = 0.69). Control subjects had an average PS = 47.9 ± 16.8, significantly different from patients' affected hemisphere at the first two measurements (p = 0.001), but not the third (p = 0.37). The PS in controls remained unchanged on repeat testing after an average 19.1 days (48.4 ± 17.1, p = 0.61). Using the last recording as the reference, the average PS in the affected hemisphere was -23.54 (-44.1, -3) degrees lower on recording one (p = 0.025), and -31.6 (-56.1, -7.1) degrees lower on recording two (p < 0.011). Changes in the unaffected hemisphere over time were nonsignificant. Discussion: These data suggest that dynamic cerebral autoregulation is impaired in the affected hemisphere throughout the first week after large-vessel ischemic stroke, and then normalizes by week two. These findings may have important implications for acute blood pressure management after stroke. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Lichtenstein postulated that the degree and extent of such fixation paralleled the resulting severity of distant neuroanatomic complications experienced and proposed that tethering of the spinal cord could lead to paraplegia. 1 and cover Collage of Lichtenstein (upper left and courtesy of University of Illinois College of Medicine [[4]]) and drawing from his 1942 paper (center and courtesy of American Medical Association, Published in the Archives of Neurology & Psychiatry [[3]]) Lichtenstein's contributions to spinal dysraphism In his manuscript [[2]] published in 1940, Lichtenstein highlighted three cases of anomalies of the spinal cord. Conclusions Lichtenstein agreed that hydrocephalus in most patients with spina bifida might lead to the formation of a Chiari malformation. [Extracted from the article]

ABSTRACT BACKGROUND Cerebral autoregulation (CA) enables the brain to maintain stable cerebral blood flow (CBF). CA can be assessed noninvasively by determining correlations between CBF velocity (CBFV) and spontaneous changes in blood pressure. Postrecording signal analysis methods have included both frequency- and time-domain methods. However, the test-retest reliability, cross-validation, and determination of normal values have not been adequately established. METHODS In 53 healthy volunteers, a transfer function analysis was applied to calculate phase shift (PS) and gain in the low frequency range (.06-.12 Hz) where CA is most apparent. Correlation analysis was used to derive mean velocity index (Mx). Intraclass correlation and bivariate correlation coefficients were applied to assess asymmetry, cross-validity, and test-retest results: The bihemispheric average PS, gain, and Mx means were 45.99+/−14.24°, .62+/−.38 cm/second/mmHg, and .41+/−.13, respectively. Gain exhibited a difference by age ( P = .03). PS, gain, and Mx values showed excellent interhemispheric correlation ( r > .8; P < .001). PS and gain showed good reliability ( R ICC = .632, L ICC = .576; P < .001). PS and Mx showed fair correlation ( r = −.37; P < .001). CONCLUSIONS CA parameters obtained by time- and frequency-domain methods correlate well, and show good interhemispheric and test-retest reliability. Group means from healthy controls may provide adequate norms for determining abnormal CA in cerebrovascular patients. [ABSTRACT FROM AUTHOR]

Background: There is a growing interest in measuring cerebral autoregulation in patients with acute brain injury. Non-invasive finger photo-plethysmography (Finapres) is the method of choice to relate arterial blood pressure to changes in cerebral blood flow. Among acutely ill patients, however, peripheral vasoconstriction often limits the use of Finapres requiring direct intravascular blood pressure measurement. We evaluated how these two different forms of blood pressure monitoring affect the parameters of dynamic cerebral autoregulation (DCA).Methods: We performed 37 simultaneous recordings of BP and cerebral blood flow velocity in 15 patients with acute brain injury. DCA was estimated in the frequency domain using transfer function analysis to calculate phase shift, gain, and coherence. In addition the mean velocity index (Mx) was calculated for assessment of DCA in the time domain.Results: The mean patient age was 58.1 ± 15.9 years, 80 % (n = 12) were women. We found good inter-method agreement between Finapres and direct intravascular measurement using Bland-Altman and correlation analyses. Finapres gives higher values for the efficiency of dynamic CA compared with values derived from radial artery catheter, as indicated by biases in the phase (26.3 ± 11.6° vs. 21.7 ± 10.5°, p = 0.001) and Mx (0.571 ± 0.137 vs. 0.649 ± 0.128, p < 0.001). Gain in the low frequency range did not significantly differ between the two arterial blood pressure methods. The average coherence between CBFV and ABP was higher when BP was measured with arterial catheter for frequencies above 0.05 Hz (0.8 vs. 0.73, p < 0.001).Conclusion: Overall, both methods yield similar results and can be used for the assessment of DCA. However, there was a small but significant difference for both mean Mx and phase shift, which would need to be adjusted for during monitoring of patients when using both methods. When available, invasive arterial blood pressure monitoring may improve accuracy and thus should be the preferred method for DCA assessment in the ICU. [ABSTRACT FROM AUTHOR]

Background: Nicardipine and labetalol are two commonly used antihypertensives for treating elevated blood pressures in the setting of intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). There are no studies comparing these two agents as continuous infusions. Methods: A retrospective chart review was conducted of patients admitted between November 2009 and January 2011 with ICH and SAH to compare effectiveness and safety between both agents. Percent time spent at goal was set as the primary outcome. The secondary outcomes included blood pressure variability, time to goal, incidence of bradycardia, tachycardia, and hypotension. Results: A total of 81 patients were available for analysis, 10 initiated on labetalol (LAB), 57 on nicardipine (NIC), and 14 required the combination of these agents (COMB) to reach goal. We found no difference between NIC, LAB, and the COMB groups in the median percent time at goal [88 % (61-98); 93 % (51-99); 66 % (25-95), ( p = NS)]. Median percentage of blood pressure variability, hypotension, and bradycardia were also comparable between groups, however, more tachycardia was observed in the COMB group versus both LAB and NIC groups (45 vs. 0 vs. 3 %; p < 0.001). Mean time to goal SBP in 24 patients who had BP readings available at 1st h of initiation was 32 ± 34 min in the NIC group and 53 ± 42 min in the LAB group ( p = 0.03). Conclusions: Both agents appear equally effective and safe for blood pressure control in SAH and ICH during the initial admission hours. A prospective study is needed to validate these findings. [ABSTRACT FROM AUTHOR]

Spontaneous intracerebral hemorrhage (sICH) continues to have high morbidity and mortality. Patients with sICH and poor mental status are at high risk of airway compromise and frequently require intubation. The traditional ventilatory weaning parameters are not reliable in patients with brain pathology. The objective of this study is to identify clinical and radiological predictors for tracheostomy in mechanically ventilated patients with sICH and to develop a scale that will accurately predict the need for tracheostomy in these patients. Only patients with supratentorial sICH intubated on the field or on admission who survived the first 3 days were included. Univariate and multivariate logistic regression analysis of clinical and radiological variables was performed, and independent predictors were identified. A risk stratification scale (TRACH Score) was developed using these independent predictors. Several independent factors were associated with early tracheostomy. The signficant clinical predictor was Glasgow Coma Scale (GCS) score ( P < 0.003). Radiological predictors were presence of hydrocephalus (OR: 12.5; P < 0.002), septum pellucidum shift (OR: 9; P < 0.025), and location of sICH in the thalamus (OR: 9; P < 0.025). The TRACH score was defined by two variables radiological scale (RScale) and Glasgow Outcome Score (GOS). TRACH score = 3 + (1 × RScale) − (0.5× GCS). The RScale (L + H + S) was obtained by adding individual points assigned according presence of: sICH location in the thalamus (L) 2 points, hydrocephalus (H) 1.5 points, septum pellucidum shift (S) 3 points. The scale was very predictive of tracheostomy needs (OR: 2.57, P < 0.0001) with an ROC = 0.92, sensitivity of 94%, positive predictive value of 83%, and negative predictive value of 95%. The TRACH Score is a practical clinical grading scale that will allow physicians to identify patients who will be needing tracheostomy. Application of this scale could have significant impact on length of stay and cost of hospitalization. [ABSTRACT FROM AUTHOR]

Methods Results Interpretation Endovascular thrombectomy (EVT) was shown to be safe and efficacious in patients with large core stroke in multiple randomized controlled trials. However, the impact of reperfusion and other procedural metrics on EVT outcomes in this population has not been well‐characterized.From the SELECT2 trial, we evaluated the association between reperfusion status, first‐pass effect (near‐complete or complete reperfusion [extended thrombolysis in cerebral infarction (eTICI) 2c‐3] in 1 pass), procedure time and primary technique (aspiration vs stent‐retriever) with functional outcomes in patients receiving EVT across ASPECTS (3 vs 4 vs 5) and core estimate strata (<70 vs ≥70ml, <100 vs ≥100ml, and <150 vs ≥150ml).Of 180 patients who received thrombectomy, 144 (80%) achieved successful reperfusion (eTICI 2b‐3) and demonstrated better clinical outcomes (adjusted generalized odds ratios [aGenOR]: 1.48, 95% confidence interval [CI]: 1.01–2.15), compared with unsuccessful reperfusion. Results were consistent across ASPECTS and core estimate strata. Additionally, complete or near‐complete reperfusion (eTICI 2c‐3) was associated with better functional outcome (aGenOR: 1.99, 95% CI: 1.33–2.97) in patients achieving successful reperfusion. Functional outcome point estimates favored those with first‐pass‐effect (42 of 167 (25%), aGenOR: 1.46, 95% CI: 0.96–2.24). Longer procedure time was associated with worse modified Rankin scale (mRS) distribution (aGenOR: 0.92, 95% CI: 0.87–0.96, p‐value = 0.001 for 10 minutes increment). Aspiration‐first technique was used in 43 of 154 (25%) patients and was not associated with higher reperfusion (88% vs 78%, p = 0.18) or better functional outcome (aGenOR: 0.74, 95% CI: 0.50–1.10) as compared with stent‐retriever first.Successful reperfusion resulted in improved clinical outcomes in large core patients across baseline ischemic core strata. Near complete or complete reperfusion was further associated with better outcomes, whereas prolonged procedures were associated with worse outcomes. Results were consistent regardless of the technique used. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

Endovascular thrombectomy (EVT) safety and efficacy in patients with large core infarcts receiving oral anticoagulants (OAC) are unknown. In the SELECT2 trial (NCT03876457), 29 of 180 (16%; vitamin K antagonists 15, direct OACs 14) EVT, and 18 of 172 (10%; vitamin K antagonists 3, direct OACs 15) medical management (MM) patients reported OAC use at baseline. EVT was not associated with better clinical outcomes in the OAC group (EVT 6 [4–6] vs MM 5 [4–6], adjusted generalized odds ratio 0.89 [0.53–1.50]), but demonstrated significantly better outcomes in patients without OAC (EVT 4 [3–6] vs MM 5 [4–6], adjusted generalized odds ratio 1.87 [1.45–2.40], p = 0.02). The OAC group had higher comorbidities, including atrial fibrillation (70% vs 17%), congestive heart failure (28% vs 10%), and hypertension (87% vs 72%), suggesting increased frailty. However, the results were consistent after adjustment for these comorbidities, and was similar regardless of the type of OACs used. Whereas any hemorrhage rates were higher in the OAC group receiving EVT (86% in OAC vs 70% in no OAC), no parenchymal hemorrhage or symptomatic intracranial hemorrhage were observed with OAC use in both the EVT and MM arms. Although we did not find evidence that the effect was due to excess hemorrhage or confounded by underlying cardiac disease or older age, OAC use alone should not exclude patients from receiving EVT. Baseline comorbidities and ischemic injury extent should be considered while making individualized treatment decisions. ANN NEUROL 2024;96:887–894 [ABSTRACT FROM AUTHOR]

Objectives Methods Results Interpretation Whereas highly cost‐effective and cost‐saving for patients with small infarcts, whether endovascular thrombectomy (EVT) remains cost‐effective in patients with extensive ischemic injury is uncertain.We conducted a model‐based cost‐effectiveness analysis from the United States, Australian, and Spanish societal perspectives, using a 7‐state Markov model, with each state defined by the modified Rankin Scale (mRS) score. Initial probabilities at 3 months were derived from the SELECT2 trial. All other model inputs, including transition probabilities, health care and non‐health care costs, and utility weights, were sourced from published literature and government websites. Our analysis included extensive sensitivity and subgroup analyses.EVT in patients with large ischemic stroke improved health outcomes and was associated with lower costs from a societal viewpoint. EVT was cost‐effective with a mean between‐group difference of 1.24 quality‐adjusted life years (QALYs), and a cost‐saving of $23,409 in the United States, $10,691 in Australia, and $30,036 in Spain, in addition to uncosted benefits in productivity for patients and carers. Subgroup analyses were directionally consistent with the overall population, notably with preserved cost‐effectiveness in older patients (≥ 70 years) and those with more severe strokes (National Institutes of Health Stroke Scale [NIHSS] ≥ 20). Sensitivity analyses were largely consistent with the base‐case results.EVT demonstrated cost‐effectiveness in patients with large core across different settings in the United States, Australia, and Spain, including older patients and those with more severe strokes. These results further support adaptation of systems of care to accommodate the expansion of thrombectomy eligibility to patients with large cores and maximize EVT benefits. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

Key Points: Question: Does endovascular thrombectomy improve functional outcome in patients with a large infarct on noncontrast computed tomographic (CT) scan within 24 hours of stroke onset? Findings: In this randomized trial of 300 patients, thrombectomy did not significantly improve 90-day functional outcome compared with medical management alone for the primary end point (adjusted difference in utility-weighted modified Rankin Scale score, 0.63). Meaning: Among patients with large infarct detected by noncontrast CT and presenting within 24 hours, thrombectomy did not significantly improve functional outcome at 90 days. Importance: Recent large infarct thrombectomy trials used heterogeneous imaging modalities and time windows for patient selection. Noncontrast computed tomographic (CT) scan is the most common stroke imaging approach. It remains uncertain whether thrombectomy is effective for patients with large infarcts identified using noncontrast CT alone within 24 hours of stroke onset. Objective: To evaluate the effect of thrombectomy in patients with a large infarct on a noncontrast CT scan within 24 hours of onset. Design, Setting, and Participants: Open-label, blinded–end point, bayesian-adaptive randomized trial with interim analyses for early stopping (futility or success) or population enrichment, which was conducted at 47 US academic and community-based stroke thrombectomy centers. Three hundred patients presenting within 24 hours with anterior-circulation, large-vessel occlusion and large infarct on noncontrast CT scan, with Alberta Stroke Program Early CT Scores of 2 to 5, were randomized to undergo thrombectomy or usual care. Enrollment occurred July 16, 2019 to October 17, 2022; final follow-up, January 25, 2023. Intervention: The intervention patients (n = 152) underwent endovascular treatment using standard thrombectomy devices and usual medical care. Control patients (n = 148) underwent usual medical care alone. Main Outcomes and Measures: The primary efficacy end point was improvement in 90-day functional outcome measured using mean utility-weighted modified Rankin Scale (UW-mRS) scores (range, 0 [death or severe disability] to 10 [no symptoms]; minimum clinically important difference, 0.3). A bayesian model determined the posterior probability that the intervention would be superior to usual care; statistical significance was a 1-sided posterior probability of.975 or more. The primary adverse event end point was 90-day mortality; secondary adverse event end points included symptomatic intracranial hemorrhage and radiographic intracranial hemorrhage. Results: The trial enrolled 300 patients (152 intervention, 148 control; 138 females [46%]; median age, 67 years), without early stopping or enrichment; 297 patients completed the 90-day follow-up. The mean (SD) 90-day UW-mRS score was 2.93 (3.39) for the intervention group vs 2.27 (2.98) for the control group with an adjusted difference of 0.63 (95% credible interval [CrI], −0.09 to 1.34; posterior probability for superiority of thrombectomy,.96). The 90-day mortality was similar between groups: 35.3% (53 of 150) for the intervention group vs 33.3% (49 of 147) for the control group. Six of 151 patients (4.0%) in the intervention group and 2 of 149 (1.3%) in the control group experienced 24-hour symptomatic intracranial hemorrhage. Fourteen patients of 148 (9.5%) in the intervention group vs 4 of 146 (2.7%) in the control group experienced parenchymal hematoma type 1 hemorrhages; 14 (9.5%) in the intervention group vs 5 (3.4%) in the control group experienced parenchymal hematoma type 2 hemorrhages; and 24 (16.2%) in the intervention group vs 9 (6.2%) in the control group experienced subarachnoid hemorrhages. Conclusions and Relevance: Among patients with a large infarct on noncontrast CT within 24 hours, thrombectomy did not demonstrate improvement in functional outcomes. But the width of the credible interval around the effect estimate includes the possibility of both no important effect and a clinically relevant benefit, so the potential role of thrombectomy with this imaging approach and time window will likely require additional study. Trial Registration: ClinicalTrials.gov Identifier: NCT03805308 This clinical trial evaluates whether endovascular thrombectomy and usual medical care vs medical care alone improves functional outcomes among patients who present within 24 hours after symptom onset with anterior-circulation, large-vessel occlusion, and large infarct detected by noncontrast CT scan. [ABSTRACT FROM AUTHOR]

Focuses on a study which described the targeted disruption of the lys2 gene of Penicillium chrysogenum (P. chrysogenum) and explored the effect of the mutation on penicillin production. Strategies for disruption of lys2 by a single crossing over; Lysine auxotrophs obtained by transformation of P. chrysogenum; Disruption of lys2 by double recombination.

Investigates effects of glucose repression of the pcbAB, pcbC and penDE genes of Penicillium chrysogenum AS-P-78. Expression of the genes in glucose-grown cultures; Effect of glucose pH on the transcription of the actin gene; Glucose control exerted on the three penicillin biosynthetic genes; Role of a regulatory mechanism independent from pH regulation.

Presents a molecular characterization of three loss-of-function mutations in the isopenicillin N-acyltransferase gene (penDE) of Penicillium chrysogenum. Npe6; Npe7; Npe8; Comparison with npe10, a deletion mutant; Production of single amino acid changes in modified N-acyltransferases; Recovery of enzyme activity following construction of hybrid molecules.

Reports that methionine increases the levels of four different transcripts of the cephalosporin genes. Increased levels of isopenicillin N synthase and deacetylcephalosporin C (DAC) acetyl-transferase in methionine-supplemented cultures; Northern (RNA) analyses of steady-state levels of transcripts in methionine-induced cells.

Background: The Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II randomized controlled trial used a tier-based management protocol based on brain tissue oxygen (PbtO2) and intracranial pressure (ICP) monitoring to reduce brain tissue hypoxia after severe traumatic brain injury. We performed a secondary analysis to explore the relationship between brain tissue hypoxia, blood pressure (BP), and interventions to improve cerebral perfusion pressure (CPP). We hypothesized that BP management below the lower limit of autoregulation would lead to cerebral hypoperfusion and brain tissue hypoxia that could be improved with hemodynamic augmentation. Methods: Of the 119 patients enrolled in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II trial, 55 patients had simultaneous recordings of arterial BP, ICP, and PbtO2. Autoregulatory function was measured by interrogating changes in ICP and PbtO2 in response to fluctuations in CPP using time-correlation analysis. The resulting autoregulatory indices (pressure reactivity index and oxygen reactivity index) were used to identify the "optimal" CPP and limits of autoregulation for each patient. Autoregulatory function and percent time with CPP outside personalized limits of autoregulation were calculated before, during, and after all interventions directed to optimize CPP. Results: Individualized limits of autoregulation were computed in 55 patients (mean age 38 years, mean monitoring time 92 h). We identified 35 episodes of brain tissue hypoxia (PbtO2 < 20 mm Hg) treated with CPP augmentation. Following each intervention, mean CPP increased from 73 ± 14 mm Hg to 79 ± 17 mm Hg (p = 0.15), and mean PbtO2 improved from 18.4 ± 5.6 mm Hg to 21.9 ± 5.6 mm Hg (p = 0.01), whereas autoregulatory function trended toward improvement (oxygen reactivity index 0.42 vs. 0.37, p = 0.14; pressure reactivity index 0.25 vs. 0.21, p = 0.2). Although optimal CPP and limits remained relatively unchanged, there was a significant decrease in the percent time with CPP below the lower limit of autoregulation in the 60 min after compared with before an intervention (11% vs. 23%, p = 0.05). Conclusions: Our analysis suggests that brain tissue hypoxia is associated with cerebral hypoperfusion characterized by increased time with CPP below the lower limit of autoregulation. Interventions to increase CPP appear to improve autoregulation. Further studies are needed to validate the importance of autoregulation as a modifiable variable with the potential to improve outcomes. [ABSTRACT FROM AUTHOR]

Ischemic stroke is responsible for significant morbidity and mortality in the United States and worldwide. Stroke treatment optimization requires emergency medical personnel to make rapid triage decisions concerning destination hospitals that may differ in their ability to provide highly time-sensitive pharmaceutical and surgical interventions. These decisions are particularly crucial in rural areas, where transport decisions can have a large impact on treatment times – often involving a trade-off between delay in pharmaceutical therapy or a delay in endovascular thrombectomy. In this work, we explore a Bayesian modeling framework to address this decision-making process, showing how these techniques may be used to fully account for diagnostic and therapeutic uncertainty. We demonstrate how these techniques can contextualize triage decision at a fine-grained spatial scale. We further show the application of this modeling approach in the US State of Iowa, using data from the Virtual International Stroke Trials Archive (VISTA), and describe potential next steps for improved triage.ABBREVIATIONLVO: large vessel occlusion; non-LVO, non-large vessel occlusion; IVT: intravenous tissue plasminogen activator; EVT: endovascular thrombectomy; CSC: comprehensive stroke centers; PSC: primary stroke centers; DS: drip and ship; MS, mothership; EMS: Emergency Medical Service; BGLM: Bayesian Generalized Linear Model; BGAM: Bayesian Generalized Additive Model; BART: Bayesian Additive Regression Trees; VISTA: Virtual International Stroke Trials Archive; NIHSS: National Institute of Health Stroke Severity Scale; ASPECTS: Alberta Stroke Programme Early CT Score; mRS, modified Rankin score; ROCAUC: Area under the receiver operating characteristic curve; ELPD: Expected Log pointwise Predictive Density; SE: Standard Error; ICA: Internal Carotid Artery; M1: Middle Cerebral Artery segment 1; M2: Middle Cerebral Artery segment 2; TIA: Transient Ischemic Attack; Cr-I: Credible Intervals; LKW: Last Known Well [ABSTRACT FROM AUTHOR]

Key Points: Question: Does the benefit from endovascular thrombectomy for patients with large ischemic strokes caused by large vessel occlusion vary by the extent of presenting ischemic injury? Findings: In an exploratory analysis of a randomized clinical trial that included 336 participants, while functional outcomes worsened as baseline ischemic core volumes increased, endovascular thrombectomy was associated with better clinical outcomes across a wide spectrum of ischemic changes and penumbra profiles on various imaging modalities compared with medical management. Meaning: Endovascular thrombectomy, compared with medical management, improved clinical outcomes across a wide spectrum of ischemic core volumes and penumbral profiles; however, large ischemic core volume is an important prognostic factor to consider when individualizing treatment decisions. Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain. Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect. Design, Setting, and Participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022. Intervention: EVT vs MM. Main Outcomes and Measures: Primary outcome was functional outcome—90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values >1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI. Results: Among 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81]), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79]). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled. Conclusion and Relevance: In this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457 This exploratory analysis of the SELECT2 trial assesses the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and the association of mismatch with clinical outcomes and endovascular treatment effect in adult patients with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery and large ischemic core in 31 global centers between October 2019 and September 2022. [ABSTRACT FROM AUTHOR]

Presidents have difficult roles regardless of systemic context and in times of crisis their work is especially complex. While the body of work on presidents generally is growing, understanding of their role in crisis is underdeveloped. In this study, we enhance research on presidential crisis leadership by applying the competing values framework to a unique set of interviews with 14 presidents from eight nations. Our results highlight the value tensions that were and are experienced by presidents during crisis as these leaders manage local needs with national guidance. The most common values discussed include control, collaborate, and create, while the value of compete was rarely referenced. [ABSTRACT FROM AUTHOR]

Objective Treatment of ruptured posterior circulation dissecting aneurysms is technically challenging with potentially high morbidity and mortality. We sought to assess the safety and feasibility of using a flow-diversion device (FDD) and a specific acute antiplatelet aggregation protocol in the management of ruptured dissecting aneurysms. Methods Subjects with ruptured dissecting aneurysms treated during a 3-year period were retrospectively identified from a prospective registry. Intraoperative complications, morbidity, and mortality were recorded. Tirofiban maintenance infusion without bolus was administered intravenously immediately after deployment of the FDD, and almost all patients were loaded with dual antiplatelet (aspirin and clopidogrel) post procedure. Clinical follow-up evaluation and modified Rankin Scale were assessed. Results Nine subjects with ruptured posterior circulation dissecting aneurysms were treated with an FDD: 5 vertebral artery, 2 basilar artery, and 2 posterior inferior cerebellar artery aneurysms. Average World Federation of Neurosurgical Societies score was 2 (range 1–5). Seven patients had external ventricular drain placed acutely for hydrocephalus. Eight patients received tirofiban infusion without bolus after FDD. No intraoperative complications occurred. Two subjects developed asymptomatic intraparenchymal hemorrhage found on surveillance noncontrast computed tomography. One subject suffered a major intraparenchymal hemorrhage and died a few days post intervention after additional anticoagulation was started for a left ventricular assist device. Follow-up modified Rankin Scale within 12 months was 0 in 3 subjects, 1 in 3 subjects, 2 in 1 subject, and 4 in 1. Conclusions Treatment of dissecting posterior circulation aneurysms with FDDs is feasible and a potential alternative to deconstructive techniques. [ABSTRACT FROM AUTHOR]

The anatomy and definition of the petroclinoid ligament (PCL) and its relationship with the abducens nerve are variably described. The goal of this study was to clarify the anatomy of the PCL and better elucidate its relationship with the abducens nerve. Thirty-six sides from 18 fresh-frozen adult cadaveric heads were used in this study. Specimens were all Caucasian and derived from 10 males and 8 females. The mean age at death was 79 years. Dissection of the PCL and abducens nerve was performed using a surgical microscope. The anterior and posterior attachments of the PCL, and position of the abducens nerve were noted. Subsequently, the width, thickness, and length of the ligament, and diameter of the abducens nerve were measured. Thirty-one sides (86.1%) were found to have a PCL, on two sides (5.6%), the PCL was ossified, and on three sides (8.3%), the PCL was absent. The width, thickness, and length of the PCL ranged from 0.54 to 3.39, 0.07 to 0.49, and 3.27 to 17.85 mm, respectively. No PCL had an anterior attachment onto the posterior clinoid process but rather, the clivus. Therefore, based on our findings, the PCL would be better described as the petroclival ligament. [ABSTRACT FROM AUTHOR]

Multiple randomised trials have shown efficacy and safety of endovascular thrombectomy in patients with large ischaemic stroke. The aim of this study was to evaluate long-term (ie, at 1 year) evidence of benefit of thrombectomy for these patients. SELECT2 was a phase 3, open-label, international, randomised controlled trial with blinded endpoint assessment, conducted at 31 hospitals in the USA, Canada, Spain, Switzerland, Australia, and New Zealand. Patients aged 18–85 years with ischaemic stroke due to proximal occlusion of the internal carotid artery or of the first segment of the middle cerebral artery, showing large ischaemic core on non-contrast CT (Alberta Stroke Program Early Computed Tomographic Score of 3–5 [range 0–10, with lower values indicating larger infarctions]) or measuring 50 mL or more on CT perfusion and MRI, were randomly assigned, within 24 h of ischaemic stroke onset, to thrombectomy plus medical care or to medical care alone. The primary outcome for this analysis was the ordinal modified Rankin Scale (range 0–6, with higher scores indicating greater disability) at 1-year follow-up in an intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT03876457) and is completed. The trial was terminated early for efficacy at the 90-day follow-up after 352 patients had been randomly assigned (178 to thrombectomy and 174 to medical care only) between Oct 11, 2019, and Sept 9, 2022. Thrombectomy significantly improved the 1-year modified Rankin Scale score distribution versus medical care alone (Wilcoxon-Mann-Whitney probability of superiority 0·59 [95% CI 0·53–0·64]; p=0·0019; generalised odds ratio 1·43 [95% CI 1·14–1·78]). At the 1-year follow-up, 77 (45%) of 170 patients receiving thrombectomy had died, compared with 83 (52%) of 159 patients receiving medical care only (1-year mortality relative risk 0·89 [95% CI 0·71–1·11]). In patients with ischaemic stroke due to a proximal occlusion and large core, thrombectomy plus medical care provided a significant functional outcome benefit compared with medical care alone at 1-year follow-up. Stryker Neurovascular. [ABSTRACT FROM AUTHOR]

Multiple brain arteriovenous malformations (bAVM) are rare neurovascular lesions usually related to genetic syndromes. Its management is not well established given its rarity. The objective of this study was to describe the clinical and angiographic features of published cases and to explore their associations with treatment outcomes. We performed a literature search of published cases in Medline and the Regional Index Medici. Additional cases were searched in our single-center registry. Data on the proportions of patients and clinical and angiographic characteristics were extracted. The study outcomes were nidal instability in patients who underwent staged treatment and radiological cure in patients who underwent treatment using any treatment modality. Logistic regression models for the study outcomes were analyzed. Data on the proportions of multiple bAVM patients were summarized with meta-analyses of proportions. We included 118 patients (reported in 68 studies) from the literature and 6 cases identified in our registry. A total of 124 patients harboring 339 bAVM nidi were included in the analyses. Differences between syndromic and non-syndromic cases were observed. The logistic regression analyses showed that angiographically occult untreated bAVM was associated (OR 14.37; 95% CI 2.17 to 95.4) with nidal instability after staged treatment, and deep (OR 5.11; 95% CI 1.51 to 17.27) and eloquent (OR 3.91; 95% CI 1.22 to 12.52) locations were associated with residual disease after treatment. Inconsistent reporting of relevant data throughout the included studies undermined the planned analyses. Some prognostic factors were found to be related to the study outcomes. Study Registration: The protocol of the systematic review was registered in PROSPERO as CRD42021245814 [ABSTRACT FROM AUTHOR]

Objective: To evaluate clinical outcomes of endovascular thrombectomy (EVT) for acute basilar artery occlusion (BAO) using population‐level data from the United States. Methods: Weighted discharge data from the National Inpatient Sample were queried to identify adult patients with acute BAO during the period of 2015 to 2019 treated with EVT or medical management only. Complex samples statistical methods and propensity‐score adjustment using inverse probability of treatment weighting (IPTW) were performed to assess clinical endpoints. Results: Among 3,950 BAO patients identified, 1,425 (36.1%) were treated with EVT [mean age 66.7 years, median National Institute of Health Stroke Scale (NIHSS) score 22]. On unadjusted analysis, 155 (10.9%) EVT patients achieved favorable functional outcomes (discharge disposition to home without services), while 515 (36.1%) experienced in‐hospital mortality, and 20 (1.4%) developed symptomatic intracranial hemorrhage (sICH). Following propensity‐score adjustment by IPTW accounting for age, stroke severity, and comorbidity burden, EVT was independently associated with favorable functional outcome [adjusted odds ratio (aOR) 1.25, 95% confidence interval (CI) 1.07, 1.46; p = 0.004], but not with in‐hospital mortality or sICH. In an IPTW‐adjusted sub‐group analysis of patients with NIHSS scores >20, EVT was associated with both favorable functional outcome (discharge disposition to home or to acute rehabilitation) (aOR 1.55, 95% CI 1.24, 1.94; p < 0.001) and decreased mortality (aOR 0.78, 95% CI 0.69, 0.89; p < 0.001), but not with sICH. Interpretation: This retrospective population‐based analysis using a large national registry provides real‐world evidence of a potential benefit of EVT in acute BAO patients. ANN NEUROL 2023;94:55–60 [ABSTRACT FROM AUTHOR]

Objective: Reperfusion therapy is highly beneficial for ischemic stroke. Reduction in both infarct growth and edema are plausible mediators of clinical benefit with reperfusion. We aimed to quantify these mediators and their interrelationship. Methods: In a pooled, patient‐level analysis of the EXTEND‐IA trials and SELECT study, we used a mediation analysis framework to quantify infarct growth and cerebral edema (midline shift) mediation effect on successful reperfusion (modified Treatment in Cerebral Ischemia ≥ 2b) association with functional outcome (modified Rankin Scale distribution). Furthermore, we evaluated an additional pathway to the original hypothesis, where infarct growth mediated successful reperfusion effect on midline shift. Results: A total 542 of 665 (81.5%) eligible patients achieved successful reperfusion. Baseline clinical and imaging characteristics were largely similar between those achieving successful versus unsuccessful reperfusion. Median infarct growth was 12.3ml (interquartile range [IQR] = 1.8–48.4), and median midline shift was 0mm (IQR = 0–2.2). Of 249 (37%) demonstrating a midline shift of ≥1mm, median shift was 2.75mm (IQR = 1.89–4.21). Successful reperfusion was associated with reductions in both predefined mediators, infarct growth (β = −1.19, 95% confidence interval [CI] = −1.51 to −0.88, p < 0.001) and midline shift (adjusted odds ratio = 0.36, 95% CI = 0.23–0.57, p < 0.001). Successful reperfusion association with improved functional outcome (adjusted common odds ratio [acOR] = 2.68, 95% CI = 1.86–3.88, p < 0.001) became insignificant (acOR = 1.39, 95% CI = 0.95–2.04, p = 0.094) when infarct growth and midline shift were added to the regression model. Infarct growth and midline shift explained 45% and 34% of successful reperfusion effect, respectively. Analysis considering an alternative hypothesis demonstrated consistent results. Interpretation: In this mediation analysis from a pooled, patient‐level cohort, a significant proportion (~80%) of successful reperfusion effect on functional outcome was mediated through reduction in infarct growth and cerebral edema. Further studies are required to confirm our findings, detect additional mediators to explain successful reperfusion residual effect, and identify novel therapeutic targets to further enhance reperfusion benefits. ANN NEUROL 2023;93:793–804 [ABSTRACT FROM AUTHOR]

The Surpass Evolve (SE) has emerged as a promising alternative treatment from the flow diverter series. The utilization of the SE has gradually increased, however, there is a scarcity of comprehensive data on the solidity of this technology in the endovascular treatment of intracranial aneurysms (IAs). This meta-analysis aimed to evaluate the safety and effectiveness of the SE flow diverter.A systematic literature search from inception to April 2024 was conducted across five databases for studies involving IAs treated with the SE. The primary effectiveness outcome was the proportion of complete aneurysm occlusion at the final follow-up, and the primary safety outcome comprised a composite of early and delayed complications. Subgroup analyses based on aneurysm size, anatomical location, and rupture status were also conducted.Our analysis included nine studies with 645 patients and 722 IAs. Effectiveness outcomes revealed an overall complete aneurysm occlusion rate of 69% (95% confidence interval (CI) = 58%–78%; I2 = 72%) and a favorable aneurysm occlusion rate of 91% (95% CI = 82%–96%; I2 = 49%). Safety outcomes demonstrated an overall complications rate of 6% (95% CI = 3%–12%; I2 = 66%), with an early complications rate of 6% (95% CI = 4%–11%; I2 = 0%), and a delayed complications rate of 0% (95% CI = 0%–7%; I2 = 0%).Our findings suggest a favorable outcome with a high rate of complete aneurysm occlusion at the last follow-up, with acceptable rates of neurological complications. Future research efforts should focus on larger, prospective studies with standardized outcome measures to further elucidate the clinical utility of the SE flow diverter in the management of IAs. [ABSTRACT FROM AUTHOR]

Introduction: Endovascular therapy has shown to be safe and effective for the treatment of cerebral dural arteriovenous fistulas; however, recurrence after complete occlusion is not uncommon, and the timing of recurrence remains unknown. Methods: A retrospective single-center cohort study was conducted from January 2005 to December 2020. Patients with high-grade (≥Borden II–Cognard IIB) dural arteriovenous fistulas treated with endovascular therapy were included in this study. Clinical and angiographic characteristics were collected for hospitalization and at follow-up. Results: A total of 51 patients with a median age of 61 years were studied; 57% were female. High-flow symptoms related to the high-flow fistula were the most common presentation (67%), and 24% presented with intracranial hemorrhage. Transverse-sigmoid (26%) and cavernous (26%) sinuses were the most common dural arteriovenous fistula locations. A total of 40 patients (70%) had middle meningeal arterial feeders and 4 (7%) had deep cerebral venous drainage. The mean number of embolization procedures per patient was 1.4. Transarterial access was the most frequent approach (61%). Onyx alone was the most common embolic agent (26%). Complete occlusion rate was achieved in 46 patients (80.1%). Last mean radiographic follow-up time was 26.7 months for all 57 dural arteriovenous fistulas. Dural arteriovenous fistula recurrence after radiographic resolution at last treatment was seen in six cases (6/46, 13.1%). Mean time for recurrence was 15.8 months. Mean time of last clinical follow-up was 46.1 months for the 51 patients (100%). A total of 10 (20%) experienced any procedural complications, among which two (4%) became major thromboembolic events. Conclusion: Endovascular therapy is safe and effective for the treatment of high-grade dural arteriovenous fistulas. Given the significant recurrence rate of embolized dural arteriovenous fistulas even after 2 years, long-term angiographic follow-up might be needed. [ABSTRACT FROM AUTHOR]

Rationale: Randomized evidence for endovascular thrombectomy safety and efficacy in patients with large core strokes is lacking. Aims: To demonstrate endovascular thrombectomy efficacy and safety in patients with large core on non-contrast CT or perfusion imaging (CT/MR) and determine if there is heterogeneity of treatment effect in large cores based on the imaging modality. Design: SELECT2 is a prospective, randomized, multi-center, assessor-blinded controlled trial with adaptive enrichment design, enrolling up to 560 patients. Procedure: Patients who meet the clinical criteria and have anterior circulation large vessel occlusions with large core on either NCCT (ASPECTS 3–5) or perfusion imaging (CTP [rCBF < 30%] and/or MRI [ADC < 620] ≥ 50 cc) will be randomized in a 1:1 ratio to undergo endovascular thrombectomy or medical management (MM) only up to 24 h of last known well. Study outcomes: The distribution of 90-day mRS scores is the primary outcome. Functional independence (mRS = 0–2) rate is a secondary outcome. Other secondary outcomes include safety (symptomatic ICH, neurological worsening, mortality) and imaging outcomes. Analysis: A normal approximation of the Wilcoxon-Mann-Whitney test (the generalized likelihood ratio test) to assess the primary outcome. Functional independence rates, safety and imaging outcomes will also be compared. Discussion: The SELECT2 trial will evaluate endovascular thrombectomy safety and efficacy in large cores on either CT or perfusion imaging and may provide randomized evidence to extend endovascular thrombectomy eligibility to larger population. Registration: ClinicalTrials.gov–NCT03876457 [ABSTRACT FROM AUTHOR]

Purpose: The treatment of deep-seeded pediatric brain arteriovenous malformations (AVMs) remains a challenging task. We describe our experience using a new detachable tip microcatheter in the embolization of brain arteriovenous malformations, pial arteriovenous fistulas, and vein of Galen malformations. We describe the safety and efficacy using a new detachable tip microcatheter in the treatment of pediatric deep brain arteriovenous malformations, pial malformations, and vein of Galen malformations. Methods: During a period of 9 months from March 2013 through January 2014, 11 pediatric patients in 14 procedures with 27 total injections were selected for treatment with a detachable tip under Food and Drug Administration (FDA) compassionate use exemption and were admitted to our department for treatment of their brain AVM using a liquid embolic agent and a detachable tip microcatheter. The ages of the patients ranged from 3 months to 18 years old. Results: Of the 27 total injections done, the tip detached in seven cases. For the 16 n-BCA injections, the tip detached six times (37.5 %), and for the 11 Onyx injections, the tip detached one time (9 %). There were no cases of premature microcatheter detachment during normal vessel navigation. Conclusions: The introduction of these detachable tip microcatheters allows for a safe and relaxed injection that permits a true circumferential occlusion, and may further permit filling a larger amount of angioarchitecture without the risk of distal migration, or vessel damage during the usual rapid removal of non detachable micocatheters. [ABSTRACT FROM AUTHOR]

Age is often used as a predictor in determining outcomes in large vessel occlusions treated with mechanical thrombectomy. However, limited data exist for octo/nonagenarian outcomes compared to younger individuals in acute basilar artery occlusions treated with thrombectomy.Patient data were obtained from the PC-SEARCH Thrombectomy Registry which consists of 444 acute basilar artery occlusions treated with mechanical thrombectomy. Individuals were dichotomized based on age (>80 and ≤80 years old). Primary outcome was defined as modified Rankin Scale of 0–3 at 90 days. Logistic and multivariate regression, as well as control-matched analysis, were performed.There were 373 and 71 patients in the younger and older cohorts, respectively. Gender, ethnicity, smoking status, atrial fibrillation, and coronary artery disease were noted to be significantly different between cohorts. At 90 days, 178 (47.7%) and 23 (32.4%) patients achieved primary outcome at 90 days (p = 0.02), however, after controlling for potentially confounding factors this association lost significance (OR 0.50 95% CI 0.24–1.05; p = 0.07). There were 84 patients included in the control matched analysis and demonstrated no significant differences on multivariate analysis between cohorts (OR 0.68 95% CI 0.25–1.84; p = 0.45).Octa/nonagenarians presenting with an acute basilar artery occlusion treated with mechanical thrombectomy can achieve acceptable rates of favorable functional outcomes compared to younger individuals with similar baseline demographic and stroke characteristics. [ABSTRACT FROM AUTHOR]

To compare safety and efficacy profiles in aneurysms treated with Pipeline Embolization Device or Pipeline Flex versus Surpass Streamline flow diverters (FDs). Patients who underwent flow diversion for aneurysm treatment at 2 centers were included. Covariates comprised patient demographics, comorbidities, and aneurysm characteristics. Metrics included number of devices, adjuvant device use, case duration, and radiation exposure. Outcomes included periprocedural complications and radiographic results at follow-up. Propensity score-matched pairs were generated using demographic and aneurysm characteristics to verify the outcomes in equally sized groups. The majority of 141 flow diversion procedures performed on 126 patients were in the anterior circulation (96%) and unruptured (93%). Operators experienced more complications placing Surpass FDs compared with Pipelines (18.2% vs. 3.1%, P = 0.005) but used fewer Surpass devices per case (1 device in all Surpass cases and range for Pipeline cases 1–7; P < 0.001). Ballooning was more frequent for Surpass (29.5% vs. 2.1%, P < 0.001). There were no differences in mortality (2.1% vs. 0, P = 1.00), intracranial hemorrhage (3.1% vs. 0, P = 0.551), or stroke (4.2% vs. 6.8%, P = 0.680). Rates of aneurysm obliteration at follow-up were similar. Propensity-matched pairs had no differences in FD deployment complications or perioperative events, yet the significant differences remained for adjuvant balloon use and number of FDs deployed. While the devices demonstrated similar safety and efficacy profiles, deployment of the Surpass Streamline was more technically challenging than Pipeline Embolization Device or Pipeline Flex. Prospective cohort studies are needed to corroborate these findings. [ABSTRACT FROM AUTHOR]

Introduction: We have demonstrated in a multicenter cohort that the COVID-19 pandemic has led to a delay in intravenous thrombolysis (IVT) among stroke patients. Whether this delay contributes to meaningful short-term outcome differences in these patients warranted further exploration. Methods: We conducted a nested observational cohort study of adult acute ischemic stroke patients receiving IVT from 9 comprehensive stroke centers across 7 U.S states. Patients admitted prior to the COVID-19 pandemic (1/1/2019–02/29/2020) were compared to patients admitted during the early pandemic (3/1/2020–7/31/2020). Multivariable logistic regression was used to estimate the effect of IVT delay on discharge to hospice or death, with treatment delay on admission during COVID-19 included as an interaction term. Results: Of the 676 thrombolysed patients, the median age was 70 (IQR 58–81) years, 313 were female (46.3%), and the median NIHSS was 8 (IQR 4–16). Longer treatment delays were observed during COVID-19 (median 46 vs 38 min, p = 0.01) and were associated with higher in-hospital death/hospice discharge irrespective of admission period (OR per hour 1.08, 95% CI 1.01–1.17, p = 0.03). This effect was strengthened after multivariable adjustment (aOR 1.15, 95% CI 1.07–1.24, p < 0.001). There was no interaction of treatment delay on admission during COVID-19 (pinteraction = 0.65). Every one-hour delay in IVT was also associated with 7% lower odds of being discharged to home or acute inpatient rehabilitation facility (aOR 0.93, 95% CI 0.89–0.97, p < 0.001). Conclusion: Treatment delays observed during the COVID-19 pandemic led to greater early mortality and hospice care, with a lower probability of discharge to home/rehabilitation facility. There was no effect modification of treatment delay on admission during the pandemic, indicating that treatment delay at any time contributes similarly to these short-term outcomes. [ABSTRACT FROM AUTHOR]

Background: While Balloon Guide Catheters (BGC) have been shown to increase the rate of reperfusion during mechanical thrombectomy (MT), its implementation with transfemoral approach is at times limited due to unfavorable vascular anatomy. Objective: to determine safety, feasibility and performance of the transradial use of 8 F BGC Flowgate 2 during mechanical thrombectomy procedures in patients with unfavorable vascular anatomies (type 3 or bovine arch) Material/Methods: We performed a retrospective cohort study of consecutive transradial mechanical thrombectomies performed with BGC Flowgate 2 between January and December 2019. Patient demographics, procedural and radiographic metrics, and clinical data were analyzed. Results: 20 (8.7%) out of 230 overall thrombectomy procedures underwent transradial approach using an 8 F BGC Flowgate. 2 Successful approach was achieved in 17/20 cases, and in 3 cases radial was switched to femoral, after failure. TICI 2 C/3 was achieved in 18 cases (90%), followed by TICI 2 b and 2a in 1 (5%) case respectively. The average number of passes was 1.8. The average radial puncture-to-first pass time was 22 min. Radial vasospasm was observed in 3/20 cases. The Flowgate 2 was found kinked in 4/20 cases (20%), all of them during right internal carotid procedures. There were no postprocedural complications at puncture site, as hematoma, pseudoaneurysm or local ischemic events Conclusion: The use of 8 F Balloon Guide Catheter during MT via transradial approach might represent an alternative in selected cases with unfavorable vascular anatomies. Its use in right ICA catheterizations was associated with a high rate of catheter kinking. [ABSTRACT FROM AUTHOR]

Background: Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis.Methods: We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days.Findings: Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years [SD 13·7], 259 [51·3%] women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76-3·33; p<0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83-3·54; p<0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0-2) than best medical therapy alone (122 [45·9%] of 266 vs 46 [19·3%] of 238; p<0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 [16·5%] of 266 vs 46 [19·3%] of 238) or symptomatic intracerebral haemorrhage (14 [5·3%] of 266 vs eight [3·3%] of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12-24 h (common OR 5·86 [95% CI 3·14-10·94]) than those randomly assigned within 6-12 h (1·76 [1·18-2·62]; pinteraction=0·0087).Interpretation: These findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6-24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6-24 h time window.Funding: Stryker Neurovascular. [ABSTRACT FROM AUTHOR]

Background: The hyperdense middle cerebral artery sign on computed tomography indicates proximal middle cerebral artery occlusion. Recent reports suggest an association between the hyperdense sign and successful reperfusion. The prognostic value of the hyperdense middle cerebral artery sign in patients receiving mechanical thrombectomy has not been extensively studied. Aims: Our study aims to evaluate the association between the hyperdense middle cerebral artery sign and functional outcome in patients with M1 occlusions that had undergone mechanical thrombectomy. Methods: We conducted a single-center retrospective observational cohort study of 102 consecutive patients presenting with acute M1 occlusions that had undergone mechanical thrombectomy. Patients were stratified into cohorts based on the presence of hyperdense middle cerebral artery sign visually assessed on computed tomography by two readers. The outcomes of interests were functional disability measured by the ordinal Modified Rankin Scale (mRS) at 90 days, mortality, reperfusion status and hemorrhagic conversion. Results: Out of the 102 patients with M1 occlusions, 71 had hyperdense middle cerebral artery sign. There was no significant difference between the cohorts in age, baseline mRS, NIHSS, ASPECTS, and time to reperfusion. The absence of hyperdense middle cerebral artery sign was associated with increased odds of being dependent or dying (higher mRS) (OR: 3.24, 95% CI: 1.30–8.06, p = 0.011) after adjusting for other significant predictors, including age, female sex, hypertension, presenting serum glucose, ASPECTS, CTA collateral score, and successful reperfusion. Conclusion: The absence of hyperdense middle cerebral artery sign is associated with worse functional outcome in patients presenting with M1 occlusions undergoing thrombectomy. [ABSTRACT FROM AUTHOR]

Introduction: Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease with prevalence of approximately 1 in 5000–10,000. We evaluated the prevalence and association of cerebrovascular and cardiovascular comorbidities in HHT patients using national database. Methods: Retrospective observational study was performed using National Inpatient Sampling (NIS) database for the year 2014. HHT patients and comorbidities were identified using ICD-9 codes. Univariate and multivariate analyses were performed using SAS. Results: Prevalence of HHT was 0.0119% with predominance in White population. Mean age of HHT patients was 59 years. Increased proportion of HHT patients had hypertension (46.8% vs 42%), anemia (28.9% vs 15.1%), chronic pulmonary disease (24.8% vs 16.4%), congestive heart failure (15.7% vs 7.5%), liver disease (7.9% vs 2.8%), migraine (4.5% vs 1.5%), and cerebrovascular malformations (0.8% vs 0.03%), whereas chronic kidney disease (12.7% vs 12.2%), headaches (1.3% vs 1.1%), seizures (0.7% vs 0.9%), transient ischemic attacks (1.06% vs 1.03%), ischemic (1.2% vs 1.0%), and hemorrhagic (0.5% vs 0.3%) strokes were similar to those without HHT. Multivariable model shows increase in cerebrovascular malformations (OR 11.04, CI 2.49–22.26, p < 0.0001), migraine (OR 3.23, CI 2.30–4.52, p < 0.0001), chronic blood loss anemia (OR 6.83, CI 5.36–8.71, p < 0.0001), congestive heart failure (OR 1.55, CI 1.26–1.91, p < 0.0001), chronic pulmonary disease (OR 1.30, CI 1.09–1.56, p = 0.0038), and hepatic disease (OR 2.63, CI 2.01–3.45, p < 0.0001) in HHT patients as compared to non-HHT patients. Conclusion: There is a need for a large prospective registry of HHT patients that can corroborate these associations and burden of cerebrovascular and cardiovascular diseases. [ABSTRACT FROM AUTHOR]