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.

Mechanical Thrombectomy for Ischemic Stroke Secondary to Large Vessel Occlusions in Patients on Extracorporeal Membrane Oxygenation.

INTRODUCTION: The use of short-term mechanical circulatory support (MCS) devices and procedures for function- and life-sustaining therapy is becoming a routine practice at many centers. Concomitant with the increasing use of MCS is the increasing recognition of acute brain injuries, including acute ischemic stroke, which may be caused by a myriad of MCS-driven factors. The aim of this case series was to document our experience with mechanical thrombectomy (MT) for ischemic stroke in extracorporeal membrane oxygenation (ECMO) patients. METHODS: We retrospectively reviewed a prospectively maintained database of patients undergoing endovascular thrombectomy for large vessel occlusion at our institution. We identified patients that were on ECMO and underwent thrombectomy. Baseline demographics and procedural and functional outcomes were collected. RESULTS: Three patients on ECMO were identified to have a large vessel occlusion and underwent thrombectomy. Two patients had an internal carotid artery terminus occlusion and one had a basilar artery occlusion. An mTICI 3 recanalization was achieved in all patients without postoperative hemorrhagic complications. Two patients achieved a 3-month mRS of 1, while one had mRS 4. CONCLUSION: Ischemic stroke can be associated with significant morbidity in MCS patients. We demonstrate that MT can be safely performed in this patient population with good outcomes.

Approaches to and outcomes of intra-arterial tPA in embolectomy for large vessel occlusion.

INTRODUCTION: Intra-arterial tissue plasminogen activator (IA tPA) is sometimes used in conjunction with aspiration catheters and stentrievers to achieve recanalization in endovascular thrombectomy (ET) for large vessel occlusion (LVO). Reports of safety and efficacy of this approach are limited by technical heterogeneity and sample size. METHODS: We retrospectively reviewed a data set of patients undergoing ET for LVO between August 2017 and September 2020 to identify those that received IA tPA. IA tPA usage, timing and dosage was at the discretion of the operative neurosurgeon. We identified three broad categories of IA tPA administration: (1) adjunctive with the first pass; (2) salvage with subsequent passes after first pass achieved incomplete revascularization; and (3) post-thrombectomy residual distal occlusions. Univariate and multivariate logistic regression were performed to test associations with recanalization, hemorrhage, and functional independence. RESULTS: Among 271 patients, 158 (58%) patients had IA tPA, of which 83 received adjuvant IA tPA, 60 received salvage IA tPA, and 15 received post-thrombectomy IA tPA for distal occlusions. There were no differences in demographics, stroke etiology and premorbid medications between these groups. Patients receiving salvage IA tPA had longer times from groin access to recanalization and more passes, as expected. On multivariate analysis neither adjunctive nor salvage IA tPA was significantly associated with recanalization, post-operative hemorrhage, or functional outcomes. On univariate analysis, patients receiving salvage IA tPA had lower rates of TICI 3 or 2b revascularization (80% vs. 89% adjunctive and 92% no IA tPA, p =  0.003) and higher rates of any postoperative hemorrhage (33% vs. 22% adjunctive and 19% no IA tPA, p =  0.003). CONCLUSIONS: In this retrospective, single-institution series, IA tPA used adjunctively or as salvage therapy in ET for LVO was not associated with recanalization, post-operative hemorrhage, or functional outcomes, suggesting IA tPA is an available modality that can be utilized in cases of recalcitrant clots.

Endovascular thrombectomy with or without intravenous thrombolysis in acute basilar artery occlusion ischemic stroke: A meta-analysis.

INTRODUCTION: It is poorly understood if endovascular thrombectomy (EVT) with or without intravenous thrombolysis (IVT) better facilitates clinical outcomes in patients with acute basilar artery occlusion (BAO) ischemic stroke. METHODS: A systematic literature review and meta-analysis was completed to investigate the outcomes of EVT with IVT versus direct EVT alone in acute BAO. Data was collected from the literature and pooled with the authors' institutional experience. The primary outcome measure was 90-day modified Rankin sale (mRS) of 0-2. Secondary measures were successful post-thrombectomy recanalization defined as mTICI ≥2b, 90-day mortality, and rate of symptomatic ICH. RESULTS: Our institutional experience combined with three multicenter studies resulted in a total of 1,127 patients included in the meta-analysis. 756 patients underwent EVT alone, while 371 were treated with EVT+IVT. Patients receiving EVT+IVT had a higher odds of achieving a 90-day mRS of ≤ 2 compared to EVT alone (OR: 1.50, 95% CI 1.15 to 1.95, P =0.002, I2 =0%). EVT+IVT also had a lower odds of 90-day mortality (OR: 0.57, 95% CI 0.37 to 0.89, P=0.01, I2=24%). There was no difference in sICH between the two groups (OR: 1.0, 95% CI: 0.56 to 1.79, P=0.99, I2=0%). There was also no difference in post-thrombectomy recanalization rates defined as mTICI ≥2b (OR: 1.11, 95% CI 0.70 to 1.75, P = 0.65, I2=37%). CONCLUSIONS: On meta-analysis, EVT with bridging IVT results in superior 90-day functional outcomes and lower 90-day mortality without increase in symptomatic ICH. These findings likely deserve further validation in a randomized controlled setting.

Endovascular Therapy is Effective for Large Vessel Occlusion Despite Concurrent Cancer.

OBJECTIVES: Ischemic stroke and concurrent cancer is increasingly recognized. However, optimal management is uncertain. As mechanical thrombectomy has become the standard of care for large vessel occlusion, more patients with cancer are presenting for embolectomy. However, it is unknown whether this subgroup has the same benefit profile described in multiple randomized trials for thrombectomy for large vessel occlusion. Our objective was to retrospectively evaluate a North American embolectomy database for safety and outcomes in patients with active cancer. MATERIALS AND METHODS: A case series of 284 embolectomies over 30 months at a single North American stroke center were divided into thrombectomy patients with active cancer(n=25) and those without active cancer (n=259). We compared patient characteristics, procedural characteristics, and procedural outcomes between patients with and without active cancer. Univariate and multivariate analysis of angiographic outcomes, postoperative hemorrhage, and functional outcome was performed. RESULTS: Of the 284 thrombectomy cases, 9% were performed on patients with active cancer. Active cancer patients had a similar recanalization grade and post-operative hemorrhage rate, compared to patients without cancer. Active cancer patients had a significantly higher 90 day mortality (40% vs 20%, p=0.018). On multivariate analysis, good functional outcome (mRS 0-2) was not impacted by active cancer. However, when mRS was evaluated as an ordinal shift analysis, worse functional outcome was associated with active cancer (OR 2.98; 95% CI, 1.29 to 6.59), greater age, NIHSS> 10, and ASPECTS<9. CONCLUSIONS: This single center retrospective series of active cancer patients undergoing thrombectomy for large vessel occlusion demonstrates similar rates of recanalization, post-operative hemorrhage, and good outcomes. While the active cancer group has a high short-term mortality, the potential to maintain quality of life in the survivors makes thrombectomy reasonable in this patient population. Awareness of ischemic stroke as a complication of cancer and the safety of thrombectomy in this population are important as this population subtype is expected to grow with improved oncology and stroke care.

Modern management of thoracic empyema.

OBJECTIVES: Historically, surgical management of empyema was performed predominantly via open thoracotomy; however, during the past decade the use of video-assisted thoracoscopic surgery (VATS) as an alternative has increased. This study retrospectively compared the outcomes and management of patients with empyema at the University of Kentucky Medical Center who had undergone VATS versus those receiving open thoracotomy to determine whether VATS decortication provided comparable results. METHODS: Adult patients who had undergone open thoracotomy or VATS decortication for empyema between 2005 and 2009 at the University of Kentucky were identified by querying the hospital's cardiothoracic surgery database. Patients were sorted by procedure on an intent-to-treat basis. Comorbid conditions, preoperative course, operative outcomes, and postoperative outcomes were compared. Quantitative data were analyzed with either an unpaired t test or the Mann-Whitney U test. Qualitative data were analyzed using the Fisher exact test. RESULTS: Fifty-three patients were identified, 18 of whom underwent VATS and 35 underwent open thoracotomy. Eight of the 18 VATS procedures (44.4%) were converted to open thoracotomy. Patients undergoing VATS had a significantly shorter median length of stay (11 vs 18 days, respectively; P = 0.044), chest tube duration (6 vs 12 days, respectively; P < 0.001), operative blood loss (55.6 vs 344 mL, respectively; P = 0.003), and fewer postoperative respiratory failures (0% vs 22.9%, respectively; P = 0.0451). The two groups did not differ significantly in overall morbidity, reoperation, mortality, or preoperative comorbidities. CONCLUSIONS: In adults, VATS offers results comparable to those of open thoracotomy, and lengths of stay, chest tube durations, and postoperative outcomes are superior. Although the conversion rate of VATS to open thoracotomy at our institution was high (38.1%) compared with studies at other institutions, the data still indicate that VATS is both a safe and reliable alternative to open thoracotomy.

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.

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.

A Simple 3D Printed Model for Intracranial Vascular Anastomosis Practice and the Rochester Bypass Training Score.

BACKGROUND AND OBJECTIVES: Surgical simulation models in cranial neurosurgery are needed to allow affordable, accessible, and validated practice in resident education. Current bypass anastomosis practice models revolve around basic tube tying or complex animal and 3-dimensional models. This study sought to design and validate a 3-dimensional printed model for intracranial anastomosis training. METHODS: A computer-aided design (CAD) generic skull was uploaded into Meshmixer (v.3.5), and a 55-mm opening was created on the right side, mimicking a standard orbitozygomatic craniotomy. The model was rotated 15° upward and 35° left, before a 10-mm square frame was added 80-mm deep to the right orbit. The CAD model was uploaded to GrabCAD and printed using a J750 PolyJet 3D printer before being paired with a vascular anastomosis kit. The model was validated with standardized assessments of residents and attendings by simulating an "M2 to P2" bypass. The Rochester Bypass Training Score (RBTS) was created to assess bypass patency, back wall suturing, and suture quality. Postsimulation survey data regarding the realism and usefulness of the simulation were collected. RESULTS: Five junior residents (Postgraduate Year 1-4), 3 senior residents (Postgraduate Year 5-7), and 2 attendings were participated. The mean operative time in minutes was as follows: junior residents 78, senior residents 33, and attendings 50. The RBTS means were as follows: junior residents 2.4, senior residents 4.0, and attendings 5.0. Participants agreed that the model was realistic, useful for improving operative technique, and would increase comfort in bypass procedures. There are a few different printing options, varying in model infill and printing material used. For this experiment, a mix of Vero plastics were used totaling $309.09 per model; however, using the more common printing material polylactic acid brings the cost to $17.27 for a comparable model. CONCLUSION: This study presents an affordable, realistic, and educational intracranial vascular anastomosis simulator and introduces the RBTS for assessment.

Outcomes of Pulsatile Tinnitus After Cerebral Venous Sinus Stenting: Systematic Review and Pooled Analysis of 616 Patients.

BACKGROUND: Pulsatile tinnitus (PT) is a debilitating condition with substantial morbidity related to quality of life. Cerebral venous sinus stenosis has recently emerged as a noninfrequent cause of PT, either in the setting of concurrent idiopathic intracranial hypertension (IIH) or due to primary venous stenosis. Venous sinus stenting (VSS) is an endovascular technique that can be used to treat venous stenosis. However, it is unclear if outcomes are different between patients with primary venogenic PT and IIH associated PT. METHODS: A systematic literature review and pooled analysis was completed to evaluate the clinical outcomes of PT in patients undergoing cerebral VSS. Outcome measures included: Improved PT, complete resolution of PT, and PT recurrence at follow-up. Subgroup analysis between patients with IIH and primary PT was completed. RESULTS: In total, 28 studies were identified with 616 patients. The proportion of improved PT symptoms after VSS had an overall pooled rate of 91.7% (confidence interval [CI]:88.1%-95.2%; I2 = 65%) and no difference between subgroups (P = 0.12). Complete resolution after VSS had an overall pooled rate of 88.6% (CI: 84.0%-93.3%; I2 = 68%) and no significant difference between subgroups (P = 0.35). Recurrent PT after stenting occurred in 6.5% of cases (CI: 1.7%-11.3%; I2 = 62%). Furthermore, subgroup analysis demonstrated that IIH patients had a significantly higher recurrence rate (10.6%; CI: 5.2%-16.1%; I2 = 26%) compared to patients treated with venous stenting for PT as the primary indication (2.0%; CI: 0.8%-4.7%; I2 = 0%) (P < 0.0001). CONCLUSIONS: Venous stenting in patients with PT results in a substantial decrease and often complete resolution of symptoms. PT is more likely to recur in patients with IIH-associated PT.

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.

"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.

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.

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.

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.

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.

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.

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.

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.