Hemoglobin Drop is Associated with Early Post-operative Stroke Following Revascularization Surgery for Moyamoya Disease.

BACKGROUND: Postoperative stroke is a potentially devastating neurological complication following surgical revascularization for Moyamoya disease. We sought to evaluate whether peri-operative hemoglobin levels were associated with the risk of early post-operative stroke following revascularization surgery in adult Moyamoya patients. METHODS: Adult patients having revascularization surgeries for Moyamoya disease between 1999-2022 were identified through single institutional retrospective review. Logistic regression analysis was used to test for the association between hemoglobin drop and early postoperative stroke. RESULTS: In all, 106 revascularization surgeries were included in the study. A stroke occurred within 7 days after surgery in 9.4% of cases. There were no significant associations between the occurrence of an early postoperative stroke and patient age, gender, or race. Mean postoperative hemoglobin drop was greater in patients who suffered an early postoperative stroke compared with patients who did not (2.3±1.1 g/dL vs. 1.3±1.1 g/dL, respectively; P=0.034). Patients who experienced a hemoglobin drop post-operatively had 2.03 times greater odds (95% confidence interval, 1.06-4.23; P=0.040) of having a stroke than those whose hemoglobin levels were stable. Early postoperative stroke was also associated with an increase in length of hospital stay (P<0.001), discharge to a rehabilitation facility (P=0.014), and worse modified Rankin scale at 1 month (P=0.001). CONCLUSION: This study found a significant association between hemoglobin drop and early postoperative stroke following revascularization surgery in adult patients with Moyamoya disease. Based on our findings, it may be prudent to avoid hemoglobin drops in Moyamoya patients undergoing surgical revascularization.

Prolonged venous transit on perfusion imaging is associated with higher odds of mortality in successfully reperfused patients with large vessel occlusion stroke.

BACKGROUND: Poor venous outflow (VO) profiles are associated with unfavorable outcomes in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO), despite achieving successful reperfusion. The objective of this study is to assess the association between mortality and prolonged venous transit (PVT), a novel visual qualitative VO marker on CT perfusion (CTP) time to maximum (Tmax) maps. METHODS: We performed a retrospective analysis of prospectively collected data from consecutive adult patients with AIS-LVO with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/2c/3). PVT+ was defined as Tmax ≥10 s timing on CTP Tmax maps in at least one of the following: superior sagittal sinus (proximal venous drainage) and/or torcula (deep venous drainage). PVT- was defined as lacking this in both regions. The primary outcome was mortality at 90 days. In a 1:1 propensity score-matched cohort, regressions were performed to determine the effect of PVT on 90-day mortality. RESULTS: In 127 patients of median (IQR) age 71 (64-81) years, mortality occurred in a significantly greater proportion of PVT+ patients than PVT- patients (32.5% vs 12.6%, P=0.01). This significant difference persisted after matching (P=0.03). PVT+ was associated with a significantly increased likelihood of 90-day mortality (OR 1.22 (95% CI 1.02 to 1.46), P=0.03) in the matched cohort. CONCLUSIONS: PVT+ was significantly associated with 90-day mortality despite successful reperfusion therapy in patients with AIS-LVO. PVT is a simple VO profile marker with potential as an adjunctive metric during acute evaluation of AIS-LVO patients. Future studies will expand our understanding of using PVT in the evaluation of patients with AIS-LVO.

Soluble PD-L1 reprograms blood monocytes to prevent cerebral edema and facilitate recovery after ischemic stroke.

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 Ly6Clo, CD43hi, 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.

Perioperative Infection After Aneurysmal Subarachnoid Hemorrhage: Risk Factors, Causative Pathogens, and Long-Term Outcomes.

BACKGROUND AND OBJECTIVES: Nosocomial infections are the most common complication among critically ill patients and contribute to poor long-term outcomes. Patients with aneurysmal subarachnoid hemorrhage (aSAH) are highly susceptible to perioperative infections, yet it is unclear what factors influence infection onset and functional recovery. The objective was to investigate risk factors for perioperative infections after aSAH and relate causative pathogens to patient outcomes. METHODS: Clinical records were obtained for 194 adult patients with aSAH treated at our institution from 2016 to 2020. Demographics, clinical course, complications, microbiological reports, and outcomes were collected. χ 2 , univariate, and multivariate logistic regression analyses were used to analyze risk factors. RESULTS: Nearly half of the patients developed nosocomial infections, most frequently pneumonia and urinary tract infection. Patients with infections had longer hospital stays, higher rates of delayed cerebral ischemia, and worse functional recovery up to 6 months after initial hemorrhage. Independent risk factors for pneumonia included male sex, comatose status at admission, mechanical ventilatory use, and longer admission, while those for urinary tract infection included older age and longer admission. Staphylococcus , Klebsiella , and Enterococcus spp. were associated with poor long-term outcome. Certain pathogenic organisms were associated with delayed cerebral ischemia. CONCLUSION: Perioperative infections are highly prevalent among patients with aSAH and are related to adverse outcomes. The risk profiles for nosocomial infections are distinct to each infection type and causative organism. Although strong infection control measures should be universally applied, patient management must be individualized in the context of specific infections.

Redefining CT perfusion-based ischemic core estimates for the ghost core in early time window stroke.

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.

Pretreatment parameters associated with hemorrhagic transformation among successfully recanalized medium vessel occlusions.

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.

Racial disparities in functional outcomes following mechanical thrombectomy in a cohort of patients with ischemic stroke.

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.

Venous thromboembolism in aneurysmal subarachnoid hemorrhage: Risk factors and timing of chemoprophylaxis.

INTRODUCTION: Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality among patients recovering from aneurysmal subarachnoid hemorrhage (aSAH). Prophylactic heparin reduces the risk of VTE, but the optimal timing for its initiation among aSAH patients remains unclear. OBJECTIVE: To conduct a retrospective study assessing risk factors for VTE and optimal timing of chemoprophylaxis in patients treated for aSAH. METHODS: From 2016-2020, 194 adult patients were treated for aSAH at our institution. Patient demographics, clinical diagnoses, complications, pharmacologic interventions, and outcomes were recorded. Risk factors for symptomatic VTE (sVTE) were analyzed via Chi-squared, univariate, and multivariate regression. RESULTS: In total 33 patients presented with sVTE (25 DVT, 14 PE). Patients with sVTE had longer hospital stays (p < 0.01) and worse outcomes at one-month (p < 0.01) and three-month follow-up (p = 0.02). Univariate predictors of sVTE included male sex (p = 0.03), Hunt Hess score (p = 0.01), Glasgow Coma scale (p = 0.02), intracranial hemorrhage (p = 0.03), hydrocephalus requiring external ventricular drain (EVD) placement (p < 0.01), and mechanical ventilation (p < 0.01). Only hydrocephalus requiring EVD (p = 0.01) and ventilator use (p = 0.02) remained significant upon multivariate analysis. Patients with delayed heparin introduction were significantly more likely to sustain sVTE on univariate analysis (p = 0.02) with a trend-level significance on multivariate analysis (p = 0.07). CONCLUSIONS: Patients with aSAH are more likely to develop sVTE following use of perioperative EVD or mechanical ventilation. sVTE leads to longer hospital stays and worse outcomes among patients treated for aSAH. Delayed heparin initiation increases the risk of sVTE. Our results may help guide surgical decision-making during recovery from aSAH and improve VTE-related postoperative outcomes.

Endovascular Thrombectomy versus Endovascular Thrombectomy Preceded by Intravenous Thrombolysis: A Systematic Review and Meta-Analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

No Delayed Ruptures on Long-Term Follow-Up of a Case Series of Persistently Filling Saccular Internal Carotid Artery Aneurysms After Flow Diversion With the Pipeline Embolization Device.

BACKGROUND AND OBJECTIVES: Flow diversion of intracranial aneurysms results in high occlusion rates. However, 10% to 20% remain persistently filling at 1 year. Often, these are retreated, but benefits of retreatment are not well established. A better understanding of the long-term rupture risk of persistently filling aneurysms after flow diversion is needed. METHODS: Our institutional database of 974 flow diversion cases was queried for persistently filling saccular aneurysms of the clinoidal, ophthalmic, and communicating segments of the internal carotid artery treated with the pipeline embolization device (PED, Medtronic). Persistent filling was defined as continued flow into the aneurysm on 1 year catheter angiogram. The clinical record was queried for retreatments and delayed ruptures. Clinical follow-up was required for at least 2 years. RESULTS: Ninety-four persistent aneurysms were identified. The average untreated aneurysm size was 5.6 mm. A branch vessel originated separately in 55% of cases from the body of the aneurysm in 10.6% of cases and from the neck in 34% of cases. Eighteen percent of aneurysms demonstrated >95% filling at 1 year, and 61% were filling 5% to 95% of their original size. The mean follow-up time was 4.9 years, including 41 cases with >5 years. No retreatment was undertaken in 91.5% of aneurysms. There were no cases of delayed subarachnoid hemorrhage. CONCLUSION: Among saccular internal carotid artery aneurysms treated with PED that demonstrated persistent aneurysm filling at 1 year, there were no instances of delayed rupture on long-term follow-up. These data suggest that observation may be appropriate for continued aneurysm filling at least in the first several years after PED placement.

Surgery or Endovascular Treatment in Patients with Anterior Communicating Artery Aneurysm: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Although randomized controlled trials have compared surgery versus endovascular treatment for intracranial aneurysms, the literature is sparse in terms of subgroup analysis for anterior communicating artery (ACoA) aneurysm management. This systematic review and meta-analysis sought to compare surgical versus endovascular treatment for ACoA aneurysms. METHODS: Medline, PubMed, and Embase were searched from inception to December 12, 2022. Primary outcomes were post-treatment modified Rankin Scale (mRS) >2 and mortality. Secondary outcomes were aneurysm obliteration, retreatment and recurrence, rebleeding, technical failure, vessel rupture, aneurysmal subarachnoid hemorrhage-related hydrocephalus, symptomatic vasospasm, and stroke. RESULTS: Eighteen studies yielded 2368 patients, from which 1196 (50.5%) and 1172 (49.4%) patients underwent surgery and endovascular treatment, respectively. The odds ratio (OR) of mortality was similar in total (OR = 0.92 [0.63-1.37], P = 0.69), ruptured (OR = 0.92 [0.62-1.36], P = 0.66), and unruptured cohorts (OR = 1.58 [0.06-39.60], P = 0.78). The OR of mRS > 2 was similar in total (OR = 0.75 [0.50-1.13], P = 0.17), ruptured (OR = 0.77 [0.49-1.20], P = 0.25), and unruptured cohorts (OR = 0.64 [0.21-1.96], P = 0.44). The OR of obliteration was higher with surgery in the total (OR = 2.52 [1.49-4.27], P = 0.0008) and ruptured cohorts (OR = 2.61 [1.33-5.10], P = 0.005) and unruptured group (OR = 3.46 [1.30-9.20], P = 0.01). The OR of retreatment was lower with surgery in the total (OR = 0.37 [0.17-0.76], P = 0.007) and ruptured cohorts (OR = 0.31 [0.11-0.89], P = 0.03), thought it was similar in the unruptured group (OR = 0.51 [0.08-3.03], P = 0.46). The OR of recurrence was lower with surgery in the total (OR = 0.22 [0.10, 0.47], P = 0.0001), ruptured (OR = 0.16 [0.03, 0.90], P = 0.04), and mixed (un) ruptured cohorts (OR = 0.22 [0.09-0.53], P = 0.0009). The OR of rebleeding in ruptured group was similar (OR = 0.66 [0.29-1.52], P = 0.33). The ORs of other outcomes were similar. CONCLUSIONS: ACoA aneurysms may be safely treated with either surgery or endovascular treatment, although microsurgical clipping demonstrates higher obliteration rates and lower rates of retreatment and recurrence.

Microsurgery Versus Stereotactic Radiosurgery for Treatment of Patients With Brain Arteriovenous Malformation: A Systematic Review and Meta-Analysis.

BACKGROUND: Treatment decision-making for brain arteriovenous malformations (bAVMs) with microsurgery or stereotactic radiosurgery (SRS) is controversial. OBJECTIVE: To conduct a systematic review and meta-analysis to compare microsurgery vs SRS for bAVMs. METHOD: Medline and PubMed were searched from inception to June 21, 2022. The primary outcomes were obliteration and follow-up hemorrhage, and secondary outcomes were permanent neurological deficit, worsened modified Rankin scale (mRS), follow-up mRS > 2, and mortality. The GRADE approach was used for grading the level of evidence. RESULTS: Eight studies were included, which yielded 817 patients, of which 432 (52.8%) and 385 (47.1%) patients underwent microsurgery and SRS, respectively. Two cohorts were comparable in age, sex, Spetzler-Martin grade, nidus size, location, deep venous drainage, eloquence, and follow-up. In the microsurgery group, the odds ratio (OR) of obliteration was higher (OR = 18.51 [11.05, 31.01], P < .000001, evidence: high) and the hazard ratio of follow-up hemorrhage was lower (hazard ratio = 0.47 [0.23, 0.97], P = .04, evidence: moderate). The OR of permanent neurological deficit was higher with microsurgery (OR = 2.85 [1.63, 4.97], P = .0002, evidence: low), whereas the OR of worsened mRS (OR = 1.24 [0.65, 2.38], P = .52, evidence: moderate), follow-up mRS > 2 (OR = 0.78 [0.36, 1.7], P = .53, evidence: moderate), and mortality (OR = 1.17 [0.41, 3.3], P = .77, evidence: moderate) were comparable between the groups. CONCLUSION: Microsurgery was superior at obliterating bAVMs and preventing further hemorrhage. Despite a higher rate of postoperative neurological deficit with microsurgery, functional status and mortality were comparable with patients who underwent SRS. Microsurgery should remain a first-line consideration for bAVMs, with SRS reserved for inaccessible locations, highly eloquent areas, and medically high-risk or unwilling patients.

Middle Meningeal Artery Embolization Versus Conventional Management for Patients With Chronic Subdural Hematoma: A Systematic Review and Meta-Analysis.

BACKGROUND: The results from studies that compare middle meningeal artery (MMA) embolization vs conventional management for patients with chronic subdural hematoma are varied. OBJECTIVE: To conduct a systematic review and meta-analysis on studies that compared MMA embolization vs conventional management. METHODS: Medline, PubMed, and Embase databases were searched. Primary outcomes were treatment failure and surgical rescue; secondary outcomes were complications, follow-up modified Rankin scale > 2, mortality, complete hematoma resolution, and length of hospital stay (day). The certainty of the evidence was determined using the GRADE approach. RESULTS: Nine studies yielding 1523 patients were enrolled, of which 337 (22.2%) and 1186 (77.8%) patients received MMA embolization and conventional management, respectively. MMA embolization was superior to conventional management for treatment failure (relative risk [RR] = 0.34 [0.14-0.82], P = .02), surgical rescue (RR = 0.33 [0.14-0.77], P = .01), and complete hematoma resolution (RR = 2.01 [1.10-3.68], P = .02). There was no difference between the 2 groups for complications (RR = 0.93 [0.63-1.37], P = .72), follow-up modified Rankin scale >2 (RR = 0.78 [0.449-1.25], P = .31), mortality (RR = 1.05 [0.51-2.14], P = .89), and length of hospital stay (mean difference = -0.57 [-2.55, 1.41], P = .57). For MMA embolization, the number needed to treat for treatment failure, surgical rescue, and complete hematoma resolution was 7, 9, and 3, respectively. The certainty of the evidence was moderate to high for primary outcomes and low to moderate for secondary outcomes. CONCLUSION: MMA embolization decreases treatment failure and the need for surgical rescue without furthering the risk of morbidity and mortality. The authors recommend considering MMA embolization in the chronic subdural hematoma management.

Complications of transradial versus transfemoral access for neuroendovascular procedures: a meta-analysis.

BACKGROUND: Transradial access (TRA) has gained increased usage among neurointerventionalists. However, the overall safety profile of access site complications (ASCs) and non-access site complications (NASCs) of TRA versus transfemoral access (TFA) for neuroendovascular procedures remains unclear. METHODS: A systematic literature review and meta-analysis using a random effects model was conducted to investigate the pooled odds ratios (OR) of ASCs and NASCs. Randomized, case-control, and cohort studies comparing access-related complications were analyzed. An assessment of study heterogeneity and publication bias was also completed. RESULTS: Seventeen comparative studies met the inclusion criteria for final analysis. Overall, there was a composite ASC rate of 1.8% (49/2767) versus 3.2% (168/5222) for TRA and TFA, respectively (P<0.001). TRA was associated with a lower odds of ASC compared with TFA (OR 0.42; 95% CI 0.25 to 0.68, P<0.001, I2=31%). There was significantly lower odds of complications within the intervention and diagnostic subgroups. For NASC, TRA had a lower composite incidence of complications than TFA at 1.2% (31/2586) versus 4.2% (207/4909), P<0.001). However, on meta-analysis, we found no significant difference overall between TRA and TFA for NASCs (OR 0.79; 95% CI 0.51 to 1.22, P=0.28, I2=0%), which was also the case on subgroup analysis. CONCLUSION: On meta-analysis, the current literature indicates that TRA is associated with a lower incidence of ASCs compared with TFA, but is not associated with a lower rate of NASCs.

Pivotal trial of the Neuroform Atlas stent for treatment of posterior circulation aneurysms: one-year outcomes.

BACKGROUND: Stent-assisted coiling of wide-necked intracranial aneurysms (IAs) using the Neuroform Atlas Stent System (Atlas) has shown promising results. OBJECTIVE: To present the primary efficacy and safety results of the ATLAS Investigational Device Exemption (IDE) trial in a cohort of patients with posterior circulation IAs. METHODS: The ATLAS trial is a prospective, multicenter, single-arm, open-label study of unruptured, wide-necked, IAs treated with the Atlas stent and adjunctive coiling. This study reports the results of patients with posterior circulation IAs. The primary efficacy endpoint was complete aneurysm occlusion (Raymond-Roy (RR) class I) on 12-month angiography, in the absence of re-treatment or parent artery stenosis >50%. The primary safety endpoint was any major ipsilateral stroke or neurological death within 12 months. Adjudication of the primary endpoints was performed by an imaging core laboratory and a Clinical Events Committee. RESULTS: The ATLAS trial enrolled and treated 116 patients at 25 medical centers with unruptured, wide-necked, posterior circulation IAs (mean age 60.2±10.5 years, 81.0% (94/116) female). Stents were placed in all patients with 100% technical success rate. A total of 95/116 (81.9%) patients had complete angiographic follow-up at 12 months, of whom 81 (85.3%) had complete aneurysm occlusion (RR class I). The primary effectiveness outcome was achieved in 76.7% (95% CI 67.0% to 86.5%) of patients. Overall, major ipsilateral stroke and secondary persistent neurological deficit occurred in 4.3% (5/116) and 1.7% (2/116) of patients, respectively. CONCLUSIONS: In the ATLAS IDE posterior circulation cohort, the Neuroform Atlas Stent System with adjunctive coiling demonstrated high rates of technical and safety performance. Trial registration number https://clinicaltrials.gov/ct2/show/NCT02340585.

Microsurgical resection versus stereotactic radiosurgery for low-grade intracranial arteriovenous malformations: A 27-year institutional experience.

The role of microsurgery and radiosurgery in the management of low-grade (Spetzler-Martin grade 1 and 2) arteriovenous malformations (AVMs) remains controversial. We aimed to compare outcomes of low-grade AVMs following microsurgery and radiosurgery using a database of AVM patients presenting between 1990 and 2017. Procedure-related complications, obliteration, and functional status at last follow-up were compared between groups. Hemorrhage-free survival was compared using Kaplan-Meier analysis with subgroup analyses by rupture status on presentation. The study involved 233 patients, of which 113 and 120 were treated with microsurgery and radiosurgery, respectively. The complication rates were statistically comparable between both treatment modalities. Mean follow-up time was 5.1 ± 5.2 years. In the complete cohort, there was no significant difference in hemorrhage-free survival between microsurgery and radiosurgery (log-rank p = 0.676, Breslow p = 0.493). When excluding procedure-related hemorrhage and partial resection, hemorrhage-free survival was significantly higher in the surgically treated cohort (log-rank = 0.094, Breslow p = 0.034). The obliteration rate was significantly higher in the surgical cohort (96% vs. 57%, p < 0.001), while functional status was similar. Microsurgery may offer superior hemorrhage-free survival in the early post-treatment period and demonstrates equivalent long-term hemorrhage control and functional outcome at 5 years compared to radiosurgery with nearly complete obliteration rates. Persistent neurologic deficits following microsurgery and symptomatic cerebral edema represent important treatment risks despite low SM grading. Appropriate patient selection even when dealing with low-grade AVMs is advised, as judicious patient selection and emphasis on technical success can minimize procedure-related hemorrhage and the incidence of subtotal resection.

Neuroprotective Role of Acidosis in Ischemia: Review of the Preclinical Evidence.

Efforts to develop effective neuroprotective therapies for ischemic stroke have had little success to date. One promising approach to neuroprotection is ischemic postconditioning, which utilizes brief bouts of ischemia after acute ischemic stroke to elicit neuroprotection, although the mechanism is largely unknown. As the primary components of transient ischemia are local hypoxia and acidosis, and hypoxic postconditioning has had little success, it is possible that the acidosis component may be the primary driver. To address the evidence behind this, we performed a systematic review of preclinical studies focused on the neuroprotective role of transient acidosis after ischemia. Animal studies demonstrated that mild-to-moderate acidosis after ischemic events led to better functional neurologic outcomes with reduced infarct volumes, while severe acidosis often led to cerebral edema and worse functional outcomes. In vitro studies demonstrated that mild-to-moderate acidosis improves neuronal survival largely through two means: (1) inhibition of harmful superoxide formation in the excitotoxic pathway and (2) remodeling neuronal mitochondria to allow for efficient ATP production (i.e., oxidative phosphorylation), even in the absence of oxygen. Similar to the animal studies, acidotic postconditioning in humans would entail short cycles of carbon dioxide inhalation, which has already been demonstrated to be safe as part of a hypercapnic challenge when measuring cerebrovascular reactivity. Due to the preclinical efficacy of acidotic postconditioning, its relatively straightforward translation into humans, and the growing need for neuroprotective therapies, future preclinical studies should focus on filling the current knowledge gaps that are currently restricting the development of phase I/II clinical trials.

Epidemiology and outcomes of pediatric intracranial aneurysms: comparison with an adult population in a 30-year, prospective database.

OBJECTIVE: Pediatric intracranial aneurysms are rare. Most large series in the last 15 years reported on an average of only 39 patients. The authors sought to report their institutional experience with pediatric intracranial aneurysms from 1991 to 2021 and to compare pediatric patient and aneurysm characteristics with those of a contemporaneous adult cohort. METHODS: Pediatric (≤ 18 years of age) and adult patients with one or more intracranial aneurysms were identified in a prospective database. Standard epidemiological features and outcomes of each pediatric patient were retrospectively recorded. These results were compared with those of adult aneurysm patients managed at a single institution over the same time period. RESULTS: From a total of 4500 patients with 5150 intracranial aneurysms admitted over 30 years, there were 47 children with 53 aneurysms and 4453 adults with 5097 aneurysms; 53.2% of children and 36.4% of adults presented with a subarachnoid hemorrhage (SAH). Pediatric aneurysms were significantly more common in males, more likely giant (≥ 25 mm), and most frequently located in the middle cerebral artery. Overall, 85.1% of the pediatric patients had a modified Rankin Scale score ≤ 2 at the last follow-up (with a mean follow-up of 65.9 months), and the pediatric mortality rate was 10.6%; all 5 patients who died had an SAH. The recurrence rate of treated aneurysms was 6.7% (1/15) in the endovascular group but 0% (0/31) in the microsurgical group. No de novo aneurysms occurred in children (mean follow-up 5.5 years). CONCLUSIONS: Pediatric intracranial aneurysms are significantly different from adult aneurysms in terms of sex, presentation, location, size, and outcomes. Future prospective studies will better characterize long-term aneurysm recurrence, rebleeds, and de novo aneurysm occurrences. The authors currently favor microsurgical over endovascular treatment for pediatric aneurysms.

Comparison of management approaches in deep-seated intracranial arteriovenous malformations: Does treatment improve outcome?

Deep-seated intracranial arteriovenous malformations (AVMs) represent a subset of AVMs characterized by variably reported outcomes regarding the risk of hemorrhage, microsurgical complications, and response to stereotactic radiosurgery (SRS). We aimed to compare outcomes of microsurgery, SRS, endovascular therapy, and conservative follow-up in deep-seated AVMs. A prospectively maintained database of AVM patients (1990-2017) was queried to identify patients with ruptured and unruptured deep-seated AVMs (extension into thalamus, basal ganglia, or brainstem). Comparisons of hemorrhage-free survival and poor functional outcome (modified Rankin scale [mRS] > 2) were performed between conservative management, microsurgery (±pre-procedural embolization), SRS (±pre-procedural embolization), and embolization utilizing multivariable Cox and logistic regression analyses controlling for univariable factors with p < 0.05. Of 789 AVM patients, 102 had deep-seated AVMs (conservative: 34; microsurgery: 6; SRS: 54; embolization: 8). Mean follow-up time was 6.1 years and did not differ significantly between management groups (p = 0.393). Complete obliteration was achieved in 49% of SRS patients. Upon multivariable analysis controlling for baseline rupture with conservative management as a reference group, embolization was associated with an increased hazard of hemorrhage (HR = 6.2, 95%CI [1.1-40.0], p = 0.037), while microsurgery (p = 0.118) and SRS (p = 0.167) provided no significant protection from hemorrhage. Controlling for baseline mRS, microsurgery was associated with an increased risk of poor outcome (OR = 9.2[1.2-68.3], p = 0.030), while SRS (p = 0.557) and embolization (p = 0.541) did not differ significantly from conservative management. Deep AVMs harbor a high risk of hemorrhage, but the benefit from intervention Remains uncertain. SRS may be a relatively more effective approach if interventional therapy is indicated.