Total brain volume is associated with severity of transverse sinus stenosis in idiopathic intracranial hypertension.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a complex neurological condition characterized by symptoms of increased intracranial pressure of unclear etiology. While transverse sinus stenosis (TSS) is often present in patients with IIH, how and why it occurs remains unclear. METHODS: IIH patients and a set of age-matched normal controls were identified from our single-center tertiary care institution from 2016 to 2024. Brain MRIs before treatment were computationally segmented and parcellated using FreeSurfer software. Extent of TSS on MR venograms was graded using the Farb scoring system. Relationship between normalized brain volume, normalized brain-to-CSF volume, and TSS was investigated. Multiple linear regression was conducted to investigate the association between continuous variables, accounting for the covariates body mass index, sex, and age. RESULTS: In total, 84 IIH patients (mean age, 29.8 years; 87% female) and 15 normal controls (mean age, 28.1 years) were included. Overall, increasing/worsening TSS was found to be significantly associated with normalized total brain volume (p=0.018, R=0.179) and brain-to-CSF ratio volume (p=0.026, R=0.184). Additionally, there was a significant difference between controls and IIH patients with mild and severe stenosis regarding normalized total brain volume (ANCOVA, p=0.023) and brain-to-CSF ratio volume (ANCOVA, p=0.034). Likewise, IIH patients with severe TSS had a significantly higher brain-to-CSF volume compared with controls (p=0.038) and compared with IIH patients with mild TSS (p=0.038). CONCLUSIONS: These findings suggest that total brain volume is associated with extent of TSS, which may reflect extramural venous compression due to enlarged brain and/or venous hypertension with associated cerebral congestion/swelling.

Endovascular therapy versus medical management for ischemic stroke presenting beyond 24 hours: Systematic review and meta-analysis.

OBJECTIVE: The ideal management for ischemic stroke presenting in the very late time window, or beyond 24 hours from onset, is poorly understood. It is unknown if endovascular therapy (EVT) or best medical management (MM) is associated with superior clinical outcomes. METHODS: A systematic literature and comparative meta-analysis was completed to evaluate the safety and efficacy of EVT vs. MM for stroke presenting beyond 24 hours. Outcome measures included: 90 day functional independence (mRS 0-2), 90 day mortality, and symptomatic intracranial hemorrhage (sICH) occurrence. A random effects model was used for quantitative synthesis. RESULTS: From the five included studies, a total of 704 patients were included with 461 treated with EVT and 243 treated with MM alone. The proportion of patients achieving functional independence was significantly higher in patients treated with EVT (34.6 %) compared to MM alone (15.9 %) (OR: 4.24; CI: 2.61-6.88, P < 0.00001; I2 =0 %). While sICH occurred more in EVT patients (6.8 %) compared to MM (2.8 %), this was not significant (OR: 1.96; CI: 0.61-6.27, P=0.26; I2 = 67 %). Lastly, 90 day morality occurred significantly less in the EVT group (24.5 %) compared to patients treated with MM (33.1 %), and with significantly lower odds (OR: 0.51; CI: 0.35-0.73, P=0.0003; I2=0 %). CONCLUSIONS: In certain patients presenting beyond 24 hours with ischemic stroke, EVT is associated with a significantly higher odds of achieving functional independence and lower odds of mortality compared with MM. While these results do not function as proof, they do encourage further research into extending the window beyond 24 hours for EVT. Randomized clinical trials are warranted to validate these findings.

Association of Extent of Transverse Sinus Stenosis With Cerebral Glymphatic Clearance in Patients With Idiopathic Intracranial Hypertension.

BACKGROUND AND OBJECTIVES: Idiopathic intracranial hypertension (IIH) is a neurologic disorder characterized by symptoms of elevated intracranial pressure in the absence of a clear cause. There is a developing theory that IIH may, in part, be related to abnormal cerebral glymphatic clearance. In addition, transverse sinus stenosis (TSS) is a common finding in IIH of unclear pathophysiologic significance. Similarly, whether or not TSS is associated with glymphatic outflow in IIH is unknown. The aim of this investigation was to explore the possible association between glymphatic outflow and extent of TSS in patients with IIH. METHODS: The study cohort consisted of patients with IIH and healthy controls who were retrospectively identified from our tertiary care institution located in upstate New York from 2016 to 2023. Patients with IIH were included if they had brain MRIs completed with sufficient sequences for analysis. Brain MRIs were computationally analyzed using diffusion tensor imaging analysis along the perivascular space technique to quantify the glymphatic function in patients with IIH. Glymphatic clearance, the primary outcome, was then correlated with the degree of TSS on MR venography using 2 different scoring systems, the 'Farb score' and 'Carvalho score.' RESULTS: Overall, 81 patients with IIH (70 [86%] female, mean age 29.8 years [SD: 8.2 years], mean BMI 41 [SD: 8.4]) and 10 normal controls were identified with sufficient imaging. Based on the Carvalho TSS score, IIH patients without TSS had significantly lower glymphatic clearance than healthy controls (mean ALPS index: 1.196 [SD: 0.05] vs 1.238 [SD: 0.04], respectively; p = 0.018). Furthermore, IIH patients with TSS had significantly lower glymphatic outflow than healthy controls (1.129 [SD: 0.07] vs 1.238 [SD: 0.04], respectively; p < 0.0001) and IIH patients without TSS (1.129 [SD: 0.07] vs 1.196 [SD: 0.05], respectively; p < 0.0001). In addition, there was a significant association between increasing extent of TSS and declining glymphatic clearance (p < 0.0001, R = 0.62). Finally, IIH patients with severe TSS had significantly lower glymphatic flow than IIH patients with mild stenosis (1.121 [SD: 0.07] vs 1.178 [SD: 0.05], respectively; p < 0.0001). These findings were similarly recapitulated using the Farb TSS scoring system. DISCUSSION: These preliminary findings suggest that the extent of TSS is associated with the degree of glymphatic clearance in IIH, providing novel insights into IIH pathophysiology. Further research is required to clarify the possible causal relationship between TSS and impaired glymphatic clearance in IIH.

Management and outcomes of cerebrovascular injuries after gunshot wounds to the cervical spine.

STUDY DESIGN: This study was a multicenter retrospective analysis of cervical spine gunshot wound (GSW) patients. OBJECTIVE: The present study was conducted to evaluate the management and outcomes of vascular injuries following GSW involving the cervical spine. SUMMARY OF BACKGROUND DATA: Gunshot wounds (GSW) injuring the cervical spine are associated with high rates of vascular injury. METHODS: Charts of patients with GSW involving the cervical spine at two Level 1 trauma centers were reviewed from 2010 to 2021 for demographics, injury characteristics, management and follow-up. Statistical analysis included T tests and ANOVA for comparisons of continuous variables and chi-square testing for categorical variables, non-parametric tests were used when indicated. Beta-binomial models were used to estimate the probabilities outcomes. Bayesian regression models were utilized to compute risk ratios (RR) and their 95 % confidence intervals (CI) to enhance the inferential robustness. RESULTS: 40 patients with cervical spine GSW and associated cerebrovascular injury were included in our analysis. 15 % of patients had Biffl grade (BG) V injuries, 50 % grade IV, and 35 % grade III-I. Angiography was performed in 35 % of patients. 5 of these patients (BG V-III) required endovascular treatment for pseudoaneurysm obliteration or parent vessel sacrifice. 7 patients (22 %) showed evidence of progression. 70 % of patients were placed on antiplatelet therapy for stroke prevention. Bayesian regression models with a skeptical prior for cerebral ischemia revealed a mean RR of 4.82 (95 % CI 1.02-14.48) in the BG V group, 0.75 (95 % CI 0.13-2.26) in the BG IV group, and 0.61 (95 % CI 0.06-2.01) in the combined BG III-I group. For demise the mean RR was 3.41 (95 % CI 0.58-10.65) in the BG V group and 1.69 (95 % CI 0.29-5.97) in the BG IV group. In the high BG (V, IV) group, 54.55 % of patients treated with antiplatelet therapy had complications. None of the patients that were treated with antiplatelet therapy in the low BG (III-I) group had complications. CONCLUSIONS: Cervical spine GSWs are associated with high-grade vascular injuries and may require early endovascular intervention. Additionally, a high rate of injury progression was seen on follow up imaging, requiring subsequent intervention. Reintervention and demise were common and observed in high BG (V, IV) groups. The incidence of stroke was low, especially in low BG (I-III) groups, suggesting that daily aspirin prophylaxis is adequate for long-term stroke prevention.

Preoperative embolization and en bloc resection of a metastatic pheochromocytoma of the cervical spine.

This is a unique case of metastatic pheochromocytoma of the cervical spine treated with preoperative embolization and subsequent en bloc resection. A 65-year-old man with metastatic pheochromocytoma presented with two weeks of worsening neck pain, left arm and leg weakness and paresthesia, and urinary incontinence. Magnetic resonance imaging showed a metastatic osseous lesion at C6 with severe stenosis and spinal cord compression. The patient underwent successful preoperative angiographic embolization with a liquid embolic agent followed by C5-C7 laminectomy, en bloc tumor resection, and C3-T2 posterior spinal fusion. Six weeks postoperatively, the patient reported improving strength and resolving neck pain and paresthesias. While there is no standard paradigm for the treatment of metastatic pheochromocytomas of the cervical spine, preoperative embolization may minimize intraoperative blood loss and hemodynamic instability during subsequent surgical resection.

Improved Cerebral Glymphatic Flow after Transvenous Embolization of CSF-Venous Fistula.

Spontaneous intracranial hypotension is characterized by symptoms of low intracranial CSF volume due to various mechanisms of CSF leakage. One such mechanism is a CSF-venous fistula, treatable with transvenous embolization resulting in substantial radiographic and clinical improvement. However, the exact mechanisms underlying these improvements, including the potential involvement of the glymphatic system, remain unclear. To noninvasively assess glymphatic clearance in spontaneous intracranial hypotension, we used an advanced MR imaging technique called the DTI along the perivascular spaces in 3 patients with CSF-venous fistula before and after embolization. All 3 patients with spontaneous intracranial hypotension initially had low glymphatic flow, which improved postembolization. Two patients with symptomatic improvement exhibited a more substantial increase in glymphatic flow compared with a patient with minimal improvement. These findings suggest a possible link between cerebral glymphatics in spontaneous intracranial hypotension pathophysiology and symptomatic improvement, warranting larger studies to explore the role of the glymphatic system in spontaneous intracranial hypotension.

Trends and predictors of decompressive craniectomy in acute ischemic stroke, 2011-2020.

INTRODUCTION: Rates of decompressive craniectomy (DC) in acute ischemic stroke (AIS) have been reported to decline over time, attributed to an increase in endovascular therapy (EVT) preventing the development of malignant cerebral edema. We sought to characterize trends in DC in AIS between 2011 and 2020. MATERIAL AND METHODS: We performed a retrospective observational study of U.S. AIS hospitalizations using the National Inpatient Sample, 2011 to 2020. We calculated rates of DC per 10,000 AIS among all AIS hospitalizations, as well as AIS hospitalizations undergoing invasive mechanical ventilation (IMV). A logistic regression to determine predictors of DC was performed. RESULTS: Of ∼4.4 million AIS hospitalizations, 0.5 % underwent DC; of ∼300,000 AIS with IMV, 5.8 % underwent DC. From 2011 to 2020, the rate of DC increased from 37.4 to 59.1 per 10,000 AIS (p < 0.001). The rate of DC in patients undergoing IMV remained stable at ∼550 per 10,000 (p = 0.088). The most important factors predicting DC were age (OR 4.88, 95 % CI 4.53-5.25), hospital stroke volume (OR 2.61, 95 % CI 2.17-3.14), hospital teaching status (OR 1.54, 95 % CI 1.36-1.75), and transfer status (OR 1.53, 95 % CI 1.41-1.66); EVT status did not predict DC. CONCLUSIONS: The rate of DC in AIS has increased between 2011 and 2020. Our findings are contrary to prior reports of decreasing DC rates over time. Increasing EVT rates do not seem to be preventing the occurrence of DC. Future research should focus on the decision-making process for both clinicians and surrogates regarding DC with consideration of long-term outcomes.

"Empty Cyst Sign" Appearance of CSF-Venous Fistula on Digital Spinal Myelography.

Cerebrospinal fluid venous fistulas (CSF-VFs) are an uncommon, yet increasingly recognized, cause of spontaneous intracranial hypotension.1-5 The workup involves magnetic resonance imaging (MRI) of the brain with and without contrast and MRI of the neuroaxis without contrast before dynamic myelography, either computed tomography or digital subtraction.6 The present case of an older woman with symptomatic intracranial hypotension is notable for the specific appearance of CSF-VFs on digital spinal myelography (Video 1). Among her numerous perineural cysts, it was the "disappearing" or "empty" cyst from which the fistula originated. The diagnosis was made using a second lateral fluoroscopy view, not typically used in digital spinal myelography, which demonstrated emptying of contrast from the T6 perineural cyst into the segmental vein at this level, or the "empty cyst sign." The patient then underwent transvenous onyx embolization with resolution of her orthostatic headaches and improvement of contrast-enhanced MRI of the brain with the Bern score decreasing from 7 to 0 at 3 months of follow-up.7 Because transvenous embolization of CSF-VFs is a relatively new procedure, the long-term outcomes of the procedure are not yet known.

Stroke emboli from patients with atrial fibrillation enriched with neutrophil extracellular traps.

Background: Recent literature has demonstrated remarkable heterogeneity in the composition of acute ischemic stroke (AIS) emboli, which may impact susceptibility to therapy. Objectives: In this study, we explored differences in proteomic composition of retrieved embolic material from patients with stroke with and without atrial fibrillation (AF) (AF+ and AF-, respectively). Methods: The full proteome of retrieved thromboembolic material from 24 patients with AIS was obtained by mass spectrometry. Known marker proteins were assigned groups representing broad classes of embolus components: red blood cells, platelets, neutrophils, eosinophils, histones, complement, and other clotting-associated proteins (eg, fibrinogen). Relative protein abundances were compared between AF+ and AF- samples. Functional implications of differences were explored with gene set enrichment analysis and Gene Ontology enrichment analysis and visualization tool. Results: One hundred sixty-six proteins were differentially expressed between AF+ and AF- specimens. Eight out of the 15 neutrophil proteins (P < .05; fold change, >2) and 4 of the 14 histone proteins were significantly enriched in AF+ emboli (P < .05; fold change, >2). Gene set enrichment analysis revealed a significant representation of proteins from published neutrophil extracellular trap (NET) proteomic gene sets. The most significantly represented functional Gene Ontology pathways in patients with AF involved neutrophil activation and degranulation (P < 1 × 10-7). Conclusion: The present analysis suggests enrichment of NETs in emboli of patients with stroke and AF. NETs are a significant though understudied structural component of thrombi. This work suggests not only unique stroke biology in AF but also potential therapeutic targets for AIS in this population.

Use of a large-bore 088 intracranial access support catheter for delivery of large intracranial devices: case series with the TracStar LDP in 125 cases.

BACKGROUND: The delivery of neuroendovascular devices requires a robust proximal access platform. This demand has previously been met with a 6Fr long sheath (8Fr guide) that is placed in the proximal internal carotid artery (ICA) or vertebral artery segments. We share our experience with the first 0.088 inch 8Fr guide catheter designed for direct intracranial access. METHODS: We retrospectively reviewed a prospectively maintained IRB-approved institutional database of the senior authors to identify all cases where the TracStar Large Distal Platform (LDP) was positioned within the intracranial vasculature, defined as within or distal to the petrous ICA, vertebral artery (V3) segments, or transverse sinus. Technical success was defined as safe placement of the TracStar LDP within or distal to the described distal vessel segments with subsequent complication-free device implantation. RESULTS: Over the 41-month study period from January 2020 to June 2023, 125 consecutive cases were identified in whom the TracStar LDP was navigated into the intracranial vasculature for triaxial delivery of large devices, 0.027 inch microcatheter and greater, for aneurysm treatment (n=108, 86%), intracranial angioplasty/stenting (n=15, 12%), and venous sinus stenting (n=2, 1.6%). All cases used a direct select catheter technique for initial guide placement (no exchange). Posterior circulation treatments occurred in 14.4% (n=18) of cases. Technical success was achieved in 100% of cases. No vessel dissections occurred in any cases. CONCLUSION: The TracStar LDP is an 0.088 inch 8Fr guide catheter that can establish direct intracranial access with an acceptable safety profile. This can be achieved in a wide range of neurointerventional cases with a high rate of technical success.

Feasibility of super-bore 0.088″ mechanical thrombectomy in M1 vessels smaller than 8 French: Experience in 20 consecutive cases.

INTRODUCTION: Superbore 0.088″ catheters provide a platform for optimizing aspiration efficiency and flow control during stroke mechanical thrombectomy procedures. New superbore catheters have the distal flexibility necessary to navigate complex neurovascular anatomy while providing the proximal support of traditional 8F catheters. The safety and feasibility of Zoom 88™ superbore angled-tip catheters in the middle cerebral artery (MCA) segments smaller than the catheter diameter have not been previously described. METHODS: Twenty consecutive cases of acute MCA mechanical thrombectomy were retrospectively identified from the senior authors' prospectively maintained Institutional Review Board-approved database, in which the Zoom 88 (Imperative Care, Campbell, CA) catheter was successfully navigated to at least the M1 segment. Patient demographics, procedural details, and periprocedural information were analyzed. Rates and averages (standard errors) are generally reported. RESULTS: The average National Institutes of Health Stroke Scale at presentation and age were 15 ± 2 and 73 ± 3 years, respectively. The M1 and M2 occlusions were evenly distributed. The average M1 measurements before thrombectomy ranged from 2.36 ± 0.07 mm proximally to 2.00 ± 0.11 mm distally, and after thrombectomy, they ranged from 2.34 ± 0.07 mm proximally to 1.97 ± 0.10 mm distally. First-pass modified thrombolysis in cerebral infarction (mTICI) 2C/3 recanalization was achieved in 40% of cases, and final mTICI 2C/3 recanalization was achieved in 90% of cases. A single case of mild vasospasm was managed with verapamil. No hemorrhagic or periprocedural complications were noted. CONCLUSION: Superbore 0.088″ catheters with flexible distal segments can be safely navigated to the MCA to augment mechanical thrombectomy even when the MCA segment is smaller than the catheter.

Immediate procedural safety of adjunctive proximal coil occlusion in middle meningeal artery embolization for chronic subdural hematomas: Experience in 137 cases.

BACKGROUND: Endovascular embolization of the middle meningeal artery (MMA) has emerged as an adjunctive and stand-alone modality for the management of chronic subdural hematomas (cSDH). We report our experience utilizing proximal MMA coil embolization to augment cSDH devascularization in MMA embolization. METHODS: MMA embolization cases with adjunctive proximal MMA coiling were retrospectively identified from a prospectively maintained IRB-approved database of the senior authors. RESULTS: Of the 137 cases, all patients (n = 89, 100%) were symptomatic and underwent an MMA embolization procedure for cSDH. 50 of the patients underwent bilateral embolizations, with 53% (n = 72) for left-sided and 47% (n = 65) for right-sided cSDH. The anterior MMA branch was embolized in 19 (14%), posterior in 16 (12%), and both in 102 (74.5%) cases. Penetration of the liquid embolic to the contralateral MMA or into the falx was present in 38 (28%) and 31 (23%) cases, respectively, and 46 (34%) cases had ophthalmic or petrous collateral (n = 41, 30%) branches. MMA branches coiled include the primary trunk (25.5%, n = 35), primary and anterior or posterior MMA trunks (20%, n = 28), or primary with the anterior and posterior trunks (54%, n = 74). A mild ipsilateral facial nerve palsy was reported, which remained stable at discharge and follow-up. Absence of anterograde flow in the MMA occurred in 137 (100%) cases, and no cases required periprocedural rescue surgery for cSDH evacuation. The average follow-up length was 170 ± 17.9 days, cSDH was reduced by 4.24 ± 0.5(mm) and the midline shift by 1.46 ± 0.27(mm). Complete resolution was achieved in 63 (46.0%) cases. CONCLUSION: Proximal MMA coil embolization is a safe technique for providing additional embolization/occlusion of the MMA in cSDH embolization procedures. Further studies are needed to evaluate the potential added efficacy of this technique.

Factors Influencing Compliance to Follow-up Visits in Orthopaedic Surgery.

BACKGROUND: Orthopaedic procedures require postoperative follow-up to maximize recovery. Missed appointments and noncompliance can result in complications and increased healthcare costs. This study investigates the relationship between patient postoperative visit attendance and the distance traveled to receive care. MATERIALS AND METHODS: A retrospective review of all surgeries performed by a single orthopaedic surgeon in 2019 at level 1 trauma center in a midsized city serving a largely rural population was completed. We excluded patients who underwent another subsequent procedure. Distance to care and time traveled were determined by the patient's address and the clinic address using Google Maps Application Programming Interface. Other variables that may affect attendance at follow-up visits were also collected. Univariate and multivariate logistic regression was done with purposeful selection. RESULTS: We identified 518 patients of whom 32 (6%) did not attend their first scheduled follow-up appointment. An additional 47 (10%) did not attend their second follow-up. In total, 79 patients (15%) did not attend one of their appointments. Younger age, male sex, Black or African American race, self-pay, Medicaid insurance, accident insurance, and increased distance were individual predictors of missing an appointment. In the final multivariate logistic regression model, male sex (OR 1.74), Black or African American race (OR 2.78), self-pay (OR 3.12), Medicaid (OR 3.05), and traveling more than 70 miles to clinic (OR 2.02) markedly predicted missing an appointment, while workers' compensation (OR 0.23) predicted attendance. DISCUSSION: Several nonmodifiable patient factors predict patient noncompliance in attending orthopaedic postoperative visits. When patients are considered at high risk of being lost to follow-up, there may be an opportunity to implement interventions to improve follow-up rate and patient outcomes, minimize patient costs, and maximize profitability for the hospital.

A telomere-targeting drug depletes cancer initiating cells and promotes anti-tumor immunity in small cell lung cancer.

There are few effective treatments for small cell lung cancer (SCLC) underscoring the need for innovative therapeutic approaches. This study focuses on exploiting telomerase, a critical SCLC dependency as a therapeutic target. A prominent characteristic of SCLC is their reliance on telomerase activity, a key enzyme essential for their continuous proliferation. Here we utilize a nucleoside analog, 6-Thio-2'-deoxyguanosine (6TdG) currently in phase II clinical trials, that is preferentially incorporated by telomerase into telomeres leading to telomere dysfunction. Using preclinical mouse and human derived models we find low intermittent doses of 6TdG inhibit tumor growth and reduce metastatic burden. Anti-tumor efficacy correlates with a reduction in a subpopulation of cancer initiating like cells (CICs) identified by their expression of L1CAM/CD133 and highest telomerase activity. 6TdG treatment also leads to activation of innate and adaptive anti-tumor responses. Mechanistically, 6TdG depletes CICs and induces type-I interferon signaling leading to tumor immune visibility by activating tumor cell STING signaling. We also observe increased sensitivity to irradiation after 6TdG treatment in both syngeneic and humanized SCLC xenograft models both of which are dependent on the presence of host immune cells. This study underscores the immune-enhancing and metastasis-reducing effects of 6TdG, employing a range of complementary in vitro and in vivo SCLC preclinical models providing a potential therapeutic approach to SCLC.

Dural arteriovenous fistula embolisation with venous remodelling following venous sinus stenting.

We report a case of the formation of a dural arteriovenous fistula (dAVF) of the transverse-sigmoid sinus following venous sinus stenting (VSS), treated with trans-arterial embolisation and venous remodelling. An obese woman in her 30s presented with persistent daily headaches after undergoing endoscopic repair of a skull base cerebrospinal fluid leak. Angiography demonstrated a focal right transverse-sigmoid sinus stenosis, and she underwent VSS of the right transverse sinus. She developed progressive pulsatile tinnitus within 3 months, and angiography demonstrated the formation of a Borden type 1 dAVF along the stent. Trans-arterial embolisation of the dAVF was performed with venous remodelling using a Copernic RC balloon. While VSS has become a promising treatment for venous sinus stenosis and idiopathic intracranial hypertension, dAVF formation is a rare but significant potential complication. Embolisation with venous remodelling can be performed to treat these lesions.

Histone content, and thus DNA content, is associated with differential in vitro lysis of acute ischemic stroke clots.

BACKGROUND: Fibrin, von Willebrand factor, and extracellular DNA from neutrophil extracellular traps all contribute to acute ischemic stroke thrombus integrity. OBJECTIVES: In this study, we explored how the proteomic composition of retrieved thromboemboli relates to susceptibility to lysis with distinct thrombolytics. METHODS: Twenty-six retrieved stroke thromboemboli were portioned into 4 segments, with each subjected to 1 hour of in vitro lysis at 37 °C in 1 of 4 solutions: tissue plasminogen activator (tPA), tPA + von Willebrand factor-cleaving ADAMTS-13, tPA + DNA-cleaving deoxyribonuclease (DNase) I, and all 3 enzymes. Lysis, characterized by the percent change in prelysis and postlysis weight, was compared across the solutions and related to the corresponding abundance of proteins identified on mass spectrometry for each of the thromboemboli used in lysis. RESULTS: Solutions containing DNase resulted in approximately 3-fold greater thrombolysis than that with the standard-of-care tPA solution (post hoc Tukey, P < .01 for all). DNA content was directly related to lysis in solutions containing DNase (Spearman's ρ > 0.39 and P < .05 for all significant histones) and inversely related to lysis in solutions without DNase (Spearman's ρ < -0.40 and P < .05 for all significant histones). Functional analysis suggests distinct pathways associated with susceptibility to thrombolysis with tPA (platelet-mediated) or DNase (innate immune system-mediated). CONCLUSION: This study demonstrates synergy of DNase and tPA in thrombolysis of stroke emboli and points to DNase as a potential adjunct to our currently limited selection of thrombolytics in treating acute ischemic stroke.

Diffusion-Weighted Imaging Reveals Impaired Glymphatic Clearance in Idiopathic Intracranial Hypertension.

BACKGROUND AND PURPOSE: The pathophysiology underlying idiopathic intracranial hypertension (IIH) remains incompletely understood. While one theory postulates impaired cerebral glymphatic clearance in IIH, there is a paucity of methods to quantify glymphatic activity in human brains. The purpose of this study was to use advanced diffusion-weighed imaging to evaluate the glymphatic clearance of IIH patients and how it may relate to clinical severity. MATERIALS AND METHODS: DWI was used to separately evaluate the diffusivity along the cerebral perivascular spaces and lateral association and projection fibers, with the degree of diffusivity used as a surrogate for glymphatic function (diffusion tensor image analysis along the perivascular space. Patients with IIH were compared with normal controls. Glymphatic clearance was correlated with several clinical metrics, including lumbar puncture opening pressure and Frisen papilledema grade (low grade: 0-2; high grade: 3-5). RESULTS: In total, 99 patients with IIH were identified and compared with 6 healthy controls. Overall, patients with IIH had significantly lower glymphatic clearance based on DWI-derived diffusivity compared with controls (P = .005). Additionally, in patients with IIH, there was a significant association between declining glymphatic clearance and increasing Frisen papilledema grade (P = .046) but no correlation between opening pressure and glymphatic clearance (P = .27). Furthermore, healthy controls had significantly higher glymphatic clearance compared with patients with IIH and low-grade papilledema (P = .015) and high-grade papilledema (P = .002). Lastly, patients with IIH and high-grade papilledema had lower glymphatic clearance compared with patients with IIH and low-grade papilledema (P = .005). CONCLUSIONS: Patients with IIH possess impaired glymphatic clearance, which is directly related to the extent of clinical severity. The DWI-derived parameters can be used for clinical diagnosis or to assess response to treatment.

Comparing Outcomes for Emergent Cranial Neurosurgical Procedures Performed "During Hours" and "After Hours".

OBJECTIVE: Surgery performed at night and on weekends is thought to be associated with increased complications. However, the impact of time of day on outcomes has not been studied within cranial neurosurgery. We aim to determine if there are differences in outcomes for cranial neurosurgery performed after hours (AH) compared with during hours (DH). METHODS: We performed a single-center retrospective study of cranial neurosurgery patients who underwent emergent surgery from January 2015 through December 2019. Surgery was considered DH if the incision occurred between 8 am and 5 pm Monday through Friday. We assessed outcome measures for differences between operations performed DH or AH. RESULTS: Three-hundred and ninety-three patients (114 DH, 279 AH) underwent surgery. There was a lower rate of return to the operating room within 30 days for AH (8.6%) compared with DH (14.0%), P = 0.03, on multivariate analysis. There were no significant differences in length of operation, estimated blood loss, improvement in Glasgow Coma Scale, intensive care unit and total hospital length of stay, 30-day readmission, 30-day mortality, and in-hospital mortality for cases performed DH compared with AH. Further subgroup analyses were performed for patients who underwent immediate surgery for subdural hematomas, with no differences noted in outcomes on multivariate analysis. CONCLUSIONS: This study suggests that operating AH does not appear to negatively impact outcomes when compared with operating DH, in cases of cranial neurosurgical emergencies. Further study assessing the impact on elective neurosurgical cases is required.

Safety and efficacy comparison of embolic agents for middle meningeal artery embolization for chronic subdural hematoma.

OBJECTIVE: To perform a systematic review and meta-analysis evaluating the efficacy of middle meningeal artery embolization in terms of both clinical and radiographic outcomes, when performed with different embolic agents. METHODS: A systematic literature review and meta-analysis was performed to evaluate the impact of embolic agents on outcomes for middle meningeal artery (MMA) embolization. The use of polyvinyl alcohol (PVA) with or without (±) coils, N-butyl cyanoacrylate (n-BCA) ± coils, and Onyx alone were separately evaluated. Primary outcome measures were recurrence, the need for surgical rescue and in-hospital periprocedural complications. RESULTS: Thirty-one studies were identified with a total of 1,134 patients, with 786 receiving PVA, 167 receiving n-BCA, and 181 patients receiving Onyx. There was no difference in the recurrence rate (5.5% for PVA, 4.5% for n-BCA, and 6.5% for Onyx, with P=0.71) or need for surgical rescue (5.0% for PVA, 4.0% for n-BCA, and 6.9% for Onyx, with P=0.89) based on the embolic agent. Procedural complications also did not differ between embolic agents (1.8% for PVA, 3.6% for n-BCA, and 1.6% for Onyx, with P=0.48). CONCLUSIONS: Rates of recurrence, need for surgical rescue, and periprocedural complication following MMA embolization are not impacted by the type of embolic agent utilized. Ongoing clinical trials may be used to further investigate these findings.