Sex and Racial Disparity in Outcome of Aneurysmal Subarachnoid Hemorrhage in the United States: A 20-Year Analysis.

BACKGROUND: Aneurysmal subarachnoid hemorrhage is associated with high rate of morbidity and mortality. We aimed to assess prognostic impact of sex, race, and ethnicity in these patients. METHODS: Nationwide Inpatient Sample (2000-2019) was used to identify patients presenting with aneurysmal subarachnoid hemorrhage as primary diagnosis. Patient age, sex, race/ethnicity, insurance status, socioeconomic status, comorbidities, type of the hospital, and treatment modality used for aneurysm repair were extracted. The previously validated Nationwide Inpatient Sample Subarachnoid Hemorrhage Severity Scale was used to estimate the clinical severity. Discharge destination and in-hospital mortality was used as outcome measured. The impact of race/ethnicity and sex on clinical outcome was analyzed using multivariate regression models. RESULTS: A total of 161 086 patients with aneurysmal subarachnoid hemorrhage were identified. Mean age was 55.0±13.8 years. Sixty-nine percent of the patients were female, 60% White patients, and 17% Black patients. There was no difference in the Nationwide Inpatient Sample Subarachnoid Hemorrhage Severity Scale score between the 2 sexes. Women had significantly lower odds of good clinical outcome (defined as discharge to home or acute rehabilitation facility; RR, 0.83 [95% CI, 0.74-0.94]; P=0.004). Hispanic patients (RR, 1.12 [95% CI, 1.07-1.17]; P<0.001) had higher odds of excellent clinical outcome compared with White patients, and lower risk of mortality were observed in Black patients (RR, 0.73 [95% CI, 0.66-0.81]) and Hispanic patients (RR, 0.78 [95% CI, 0.70-0.86]) compared with the White patients. CONCLUSIONS: In this nationally representative study, women were less likely to have excellent outcomes following aneurysmal subarachnoid hemorrhage, and White patients had disproportionately higher likelihood of worse clinical outcomes. Lower rates of mortality were seen among Black and Hispanic patients.

Dysphagia after ischemic and hemorrhagic stroke: A propensity-matched 20-year analysis of the national inpatient sample.

OBJECTIVE: Dysphagia is a common symptom of acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH), but little is known surrounding national trends of this post-stroke condition. Hence, this study aimed to identify the risk factors for dysphagia following AIS and ICH and evaluate in-hospital outcomes in these patients. METHODS: The 2000-2019 Nationwide Inpatient Sample was queried for patients admitted with AIS (ICD9 433, 43401, 43411, 43491, ICD-10 I63) and ICH (ICD9 431, 432.9, ICD-10 I61, I62.9). Univariate analysis with t-tests or chi-square performed as appropriate. A 1:1 nearest neighbor propensity score matched cohort was generated. Variables with standardized mean differences >0.1 were used in multivariable regression to generate adjusted odds ratios (AOR)/ß-coefficients for the presence of dysphagia on outcomes. RESULTS: Of 10,415,286 patients with AIS, 956,662 (9.2%) had in-hospital dysphagia. Total of 2,000,868 patients with ICH were identified; 203,511 (10.2%) had in-hospital dysphagia. Patients with dysphagia after AIS were less likely to experience in-hospital mortality (OR 0.61;95%CI: 0.60-0.63) or be discharged home (AOR 0.51;95%CI: 0.51-0.52), had increased length of stay (Beta-coefficient = 0.43 days; 95%CI: 0.36-0.50), and had increased hospital charges ($14411.96;95%CI: 13565.68-15257.44) (all p < 0.001). Patients with dysphagia after ICH were less likely to experience in-hospital mortality (AOR 0.39;95%CI: 0.37-0.4), less likely to be discharged home (AOR 0.59,95%CI:0.57-0.61), have longer hospital stay (Beta-coefficient = 1.99 days;95%CI: 1.78-2.21), and increased hospital charges ($28251.93; 95%CI: $25594.57-30909.28)(all p < 0.001). CONCLUSION: This is the first study to report on national trends in patients with dysphagia after AIS and ICH. These patients had longer hospital LOS, worse functional outcomes at discharge, and higher hospital costs.

Initial experience with minimally invasive endoscopic evacuation of intracerebral hemorrhage in the setting of radiographic herniation.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) can rapidly result in cerebral herniation, leading to poor neurologic outcomes or mortality. To date, neither decompressive hemicraniectomy (DH) nor hematoma evacuation have been conclusively shown to improve outcomes for comatose ICH patients presenting with cerebral herniation, with these patients largely excluded from clinical trials. Here we present the outcomes of a series of patients presenting with ICH and radiographic herniation who underwent emergent minimally invasive (MIS) ICH evacuation. METHODS: We reviewed our prospectively collected registry of patients undergoing MIS ICH evacuation at a single institution from 01/01/2017 to 10/01/2021. We selected all consecutive patients with Glasgow coma scale (GCS) ≤ 8 and radiographic herniation for this case series. Clinical and radiographic variables were collected, including admission GCS score, preoperative and postoperative hematoma volumes, National Institute of Health stroke scale (NIHSS) scores, and modified Rankin scale (mRS) scores at last follow-up. RESULTS: Of 176 patients with spontaneous supratentorial ICH who underwent minimally invasive endoscopic evacuation during the study time period, a total of 9 patients presented with GCS ≤ 8 and evidence of radiographic herniation. Among these patients, the mean age was 62 ± 12 years, the median GCS at presentation was 5 [IQR 4-6], the mean preoperative hematoma volume was 94 ± 44 mL, the mean time from ictus to evacuation was 12 ± 5 h, and the mean postoperative hematoma volume was 11 ± 16 mL, for a median evacuation percentage of 97% [83-99]. Three patients (33%) died, four (44%) survived with mRS 5 and two (22%) with mRS 4. Patients had a median NIHSS improvement of 5 compared to their initial NIHSS. Age was very strongly correlate to improvements in NIHSS (r2 = 0.90). CONCLUSION: Data from this initial experience suggest emergent MIS hematoma evacuation in the setting of ICH with radiographic herniation is feasible and technically effective. Further randomized studies are required to determine if such an intervention offers overall benefits to patients and their families.

Use of emerging technologies to enhance the treatment paradigm for spontaneous intraventricular hemorrhage.

The presence of intraventricular hemorrhage (IVH) portends a worse prognosis in patients presenting with spontaneous intracerebral hemorrhage (ICH). Intraventricular hemorrhage increases the rates of hydrocephalus, ventriculitis, and long-term shunt dependence. Over the past decade, novel medical devices and protocols have emerged to directly treat IVH. Presently, we review new technological adaptations to treating intraventricular hemorrhage in an effort to focus further innovation in treating this morbid neurosurgical pathology. We summarize current and historical treatments as well as innovations in IVH including novel procedural techniques, use of the Integra Surgiscope, use of the Artemis evacuator, use of BrainPath, novel catheter technology, large bore external ventricular drains, the IRRAflow, the CerebroFlo, and the future directions of the field. Technology and medical devices for both surgical and nonsurgical methods are advancing the treatment of IVH. With many promising new technologies on the horizon, prospects for improved clinical care for IVH and its etiologies remain hopeful.

TLR2 knockout protects against diabetes-mediated changes in cerebral perfusion and cognitive deficits.

The risk of cognitive decline in diabetes (Type 1 and Type 2) is significantly greater compared with normoglycemic patients, and the risk of developing dementia in diabetic patients is doubled. The etiology for this is likely multifactorial, but one mechanism that has gained increasing attention is decreased cerebral perfusion as a result of cerebrovascular dysfunction. The innate immune system has been shown to play a role in diabetic vascular complications, notably through the Toll-like receptor (TLR)-stimulated release of proinflammatory cytokines and chemokines that lead to vascular damage. TLR2 has been implicated in playing a crucial role in the development of diabetic microvascular complications, such as nephropathy, and thus, we hypothesized that TLR2-mediated cerebrovascular dysfunction leads to decreased cerebral blood flow (CBF) and cognitive impairment in diabetes. Knockout of TLR2 conferred protection from impaired CBF in early-stage diabetes and from hyperperfusion in long-term diabetes, prevented the development of endothelium-dependent vascular dysfunction in diabetes, created a hyperactive and anxiolytic phenotype, and protected against diabetes-induced impairment of long-term hippocampal and prefrontal cortex-mediated fear learning. In conclusion, these findings support the involvement of TLR2 in the pathogenesis of diabetic vascular disease and cognitive impairment.

Linagliptin treatment improves cerebrovascular function and remodeling and restores reduced cerebral perfusion in Type 2 diabetes.

The antihyperglycemic agent linagliptin, a dipeptidyl peptidase-4 (DPP-IV) inhibitor, has been shown to reduce inflammation and improve endothelial cell function. In this study, we hypothesized that DPP-IV inhibition with linagliptin would improve impaired cerebral perfusion in diabetic rats, as well as improve insulin-induced cerebrovascular relaxation and reverse pathological cerebrovascular remodeling. We further postulated that these changes would lead to a subsequent improvement of cognitive function. Male Type-2 diabetic and nondiabetic Goto-Kakizaki rats were treated with linagliptin for 4 wk, and blood glucose and DPP-IV plasma levels were assessed. Cerebral perfusion was assessed after treatment using laser-Doppler imaging, and dose response to insulin (10(-13) M-10(-6) M) in middle cerebral arteries was tested on a pressurized arteriograph. The impact of DPP-IV inhibition on diabetic cerebrovascular remodeling was assessed over a physiologically relevant pressure range, and changes in short-term hippocampus-dependent learning were observed using a novel object recognition test. Linagliptin lowered DPP-IV activity but did not change blood glucose or insulin levels in diabetes. Insulin-mediated vascular relaxation and cerebral perfusion were improved in the diabetic rats with linagliptin treatment. Indices of diabetic vascular remodeling, such as increased cross-sectional area, media thickness, and wall-to-lumen ratio, were also ameliorated; however, improvements in short-term hippocampal-dependent learning were not observed. The present study provides evidence that linagliptin treatment improves cerebrovascular dysfunction and remodeling in a Type 2 model of diabetes independent of glycemic control. This has important implications in diabetic patients who are predisposed to the development of cerebrovascular complications, such as stroke and cognitive impairment.

Cerebrovascular complications of diabetes: focus on cognitive dysfunction.

The incidence of diabetes has more than doubled in the United States in the last 30 years and the global disease rate is projected to double by 2030. Cognitive impairment has been associated with diabetes, worsening quality of life in patients. The structural and functional interaction of neurons with the surrounding vasculature is critical for proper function of the central nervous system including domains involved in learning and memory. Thus, in this review we explore cognitive impairment in patients and experimental models, focusing on links to vascular dysfunction and structural changes. Lastly, we propose a role for the innate immunity-mediated inflammation in neurovascular changes in diabetes.

Activation of Toll-like receptor 3 increases mouse aortic vascular smooth muscle cell contractility through ERK1/2 pathway.

Activation of Toll-like receptor 3 (TLR3), a pattern recognition receptor of the innate immune system, is associated with vascular complications. However, whether activation of TLR3 alters vascular contractility is unknown. We, therefore, hypothesized that TLR3 activation augments vascular contractility and activates vascular smooth muscle cell (VSMC) contractile apparatus proteins. Male mice were treated with polyinosinic-polycytidylic acid (Poly I:C group, 14 days), a TLR3 agonist; control mice received saline (vehicle, 14 days). At the end of protocol, blood pressure was measured by tail cuff method. Aortas were isolated and assessed for contractility experiments using a wire myograph. Aortic protein content was used to determine phosphorylated/total interferon regulatory factor 3 (IRF3), a downstream target of TLR3 signaling, and ERK1/2 using Western blot. We investigated the TLR3/IRF3/ERK1/2 signaling pathway and contractile-related proteins such as phosphorylated/total myosin light chain (MLC) and caldesmon (CaD) in aortic VSMC primary cultures. Poly I:C-treated mice exhibited (vs. vehicle-treated mice) (1) elevated systolic blood pressure. Moreover, Poly I:C treatment (2) enhanced aortic phenylephrine-induced maximum contraction, which was suppressed by PD98059 (ERK1/2 inhibitor), and (3) increased aortic levels of phosphorylated IRF3 and ERK1/2. Stimulation of mouse aortic VSMCs with Poly I:C resulted in increased phosphorylation of IRF3, ERK1/2, MLC, and CaD. Inhibition of ERK1/2 abolished Poly I:C-mediated phosphorylation of MLC and CaD. Our data provide functional evidence for the role of TLR3 in vascular contractile events, suggesting TLR3 as a potential new therapeutic target in vascular dysfunction and regulation of blood pressure.

Continuous Intrathecal Medication Delivery With the IRRA flow Catheter: Pearls and Early Experience.

BACKGROUND AND OBJECTIVES: Intrathecal (IT) medications are routinely introduced through catheterization of the intraventricular space or subarachnoid space. There has been sporadic use of IT medications delivered directly to the ventricle either by intermittent injection through an external ventricular drain (EVD) or by an Ommaya reservoir with a ventricular catheter. IT medication delivery through EVD has many drawbacks, including the necessary opening of a sterile system, delivery of medication in a bolus form, and requirements to clamp the EVD after medication delivery. Despite these setbacks, IT medications delivered through EVD have been used across a wide range of applications, including antibiotic delivery treatment of vasospasm with nicardipine and delivery of tissue plasminogen activator. METHODS: We used a newly developed active fluid exchange device to treat various severe conditions involved in the cerebral ventricles. Here, we present our treatment protocols and advice on the techniques related to successful active fluid exchange therapy. RESULTS: Seventy patients have been treated with our system with various conditions, including subarachnoid hemorrhage, intraventricular hemorrhage, ventriculitis, and cerebral abscess. Total complication rate was 14% with only 1 catheter occlusion and low rates of hemorrhage, infection, and spinal fluid leak. CONCLUSION: Current continuous IT medication dosages and protocols are based on reports and consensus statements evaluating intermittent instillation of medication boluses. The pharmacokinetics of continuous dosing and the therapeutic and safety profiles of the medications need to be studied in a prospective manner to evaluate the true optimal dosing standards. Furthermore, the ability to deliver continuous, sterile medications directly through an IT route will open new avenues of pharmacotherapy that were previously closed. This report serves as a basic guide for the safe and effective use of the IRRA flow active fluid exchange catheter to deliver IT medications.

United States regulatory approval of medical devices used for endovascular neurosurgery: A two-decade review of FDA regulatory files.

BACKGROUND: The evolution of neuroendovascular technologies has progressed substantially. Over the last two decades, the introduction of new endovascular devices has facilitated treatment for more patients, and as a result, the regulatory environment concerning neuroendovascular devices has evolved rapidly in response. OBJECTIVE: To examine trends in the approval of neuroendovascular devices by the United States Food and Drug Administration (FDA) over the last 20 years. METHODS: Open-access US FDA databases were queried between January 2000 and December 2022 for all devices approved by the Neurological Devices Advisory Committee. Neuroendovascular devices were manually classified and grouped by category. Device approval data, including approval times, approval pathway, and presence of predicate devices, were examined. RESULTS: A total of 3186 neurological devices were approved via various US FDA pathways during the study period. 320 (10.0%) corresponded to neuroendovascular devices, of which 301 (94.1%) were approved via the 510(k) pathway. The percentage of 510(k) pathway neuroendovascular devices increased from 6.9% to 14.3% of all neuro devices before and after 2015, respectively. There was an increase in approval times for neuroendovascular devices cleared after 2015. CONCLUSION: Over the last two decades, the neuroendovascular device armamentarium has rapidly expanded, especially after positive stroke trials in 2015. Regulatory approval times are significantly affected by device category, generation, company size, and company location, and a vast majority are approved by the 510(k) pathway. These results can guide further innovation in the endovascular device space and may act as a roadmap for future regulatory planning.

Characterization of length of stay after minimally invasive endoscopic intracerebral hemorrhage evacuation.

BACKGROUND: Minimally invasive evacuation may help ameliorate outcomes after intracerebral hemorrhage (ICH). However, hospital length of stay (LOS) post-evacuation is often long and costly. OBJECTIVE: To examine factors associated with LOS in a large cohort of patients who underwent minimally invasive endoscopic evacuation. METHODS: Patients presenting to a large health system with spontaneous supratentorial ICH qualified for minimally invasive endoscopic evacuation if they met the following inclusion criteria: age ≥18, premorbid modified Rankin Scale (mRS) score ≤3, hematoma volume ≥15 mL, and presenting National Institutes of Health Stroke Scale (NIHSS) score ≥6. Demographic, clinical, radiographic, and operative characteristics were included in a multivariate logistic regression for hospital and ICU LOS dichotomized into short and prolonged stay at 14 and 7 days, respectively. RESULTS: Among 226 patients who underwent minimally invasive endoscopic evacuation, the median intensive care unit and hospital LOS were 8 (4-15) days and 16 (9-27) days, respectively. A greater extent of functional impairment on presentation (OR per NIHSS point 1.10 (95% CI 1.04 to 1.17), P=0.007), concurrent intraventricular hemorrhage (OR=2.46 (1.25 to 4.86), P=0.02), and deep origin (OR=per point 2.42 (1.21 to 4.83), P=0.01) were associated with prolonged hospital LOS. A longer delay from ictus to evacuation (OR per hour 1.02 (1.01 to 1.04), P=0.007) and longer procedure time (OR per hour 1.91 (1.26 to 2.89), P=0.002) were associated with prolonged ICU LOS. Prolonged hospital and ICU LOS were in turn longitudinally associated with a lower rate of discharge to acute rehabilitation (40% vs 70%, P<0.0001) and worse 6-month mRS outcomes (5 (4-6) vs 3 (2-4), P<0.0001). CONCLUSIONS: We present factors associated with prolonged LOS, which in turn was associated with poor long-term outcomes. Factors associated with LOS may help to inform patient and clinician expectations of recovery, guide protocols for clinical trials, and select suitable populations for minimally invasive endoscopic evacuation.

Early and effective intracerebral hemorrhage evacuation is associated with a lower 1-year residual cavity volume and better functional outcomes.

BACKGROUND: We explored the clinical significance of the residual hematoma cavity 1 year after minimally invasive intracerebral hemorrhage (ICH) evacuation. METHODS: Patients presenting with spontaneous supratentorial ICH were evaluated for minimally invasive surgical evacuation. Inclusion criteria included age ≥18 years, preoperative hematoma volume (Hv) ≥15 mL, presenting National Institutes of Health Stroke Scale score ≥6, and premorbid modified Rankin Scale (mRS) score ≤3. Patients with longitudinal CT scans at least 3 months after evacuation were included in the study. Remnant cavity volumes (Cv) after evacuation were computed using semi-automatic volumetric segmentation software. Relative cavity volume (rCv) was defined as the ratio of the preoperative Hv to the remnant Cv. RESULTS: 108 patients with a total of 484 head CT scans were included in the study. The median postoperative Cv was 2.4 (IQR 0.0-11) mL, or just 6% (0-33%) of the preoperative Hv. The median residual Cv on the final head CT scan a median of 13 months (range 11-27 months) after surgery had increased to 9.4 (IQR 3.1-18) mL, or 25% (10-60%) of the preoperative Hv. rCv on the final head CT scan was negatively associated with measures of operative success including evacuation percentage, postoperative Hv ≤15 mL, and decreased time from ictus to evacuation. rCv on the final head CT scan was also associated with a worse 6-month functional outcome (ß per mRS point 17.6%, P<0.0001; area under the receiver operating characteristic curve 0.91). CONCLUSION: After minimally invasive ICH evacuation the hematoma lesion decompresses significantly, with a residual Cv just 6% of the original lesion, but then gradually increases in size over time. Early and high percentage ICH evacuation may reduce the remnant Cv over time which, in turn, is associated with improved functional outcomes.

Transcranioplasty Ultrasonography Through a Sonolucent Prosthesis: A Review of Feasibility, Safety, and Benefits.

Data on the effectiveness of transcranioplasty ultrasonography through sonolucent cranioplasty (SC) are new and heterogeneous. We performed the first systematic literature review on SC. Ovid Embase, Ovid Medline, and Web of Science Core Collection were systematically searched and published full text articles detailing new use of SC for the purpose of neuroimaging were critically appraised and extracted. Of 16 eligible studies, 6 reported preclinical research and 12 reported clinical experiences encompassing 189 total patients with SC. The cohort age ranged from teens to 80s and was 60% (113/189) female. Sonolucent materials in clinical use are clear PMMA (polymethylmethacrylate), opaque PMMA, polyetheretherketone, and polyolefin. Overall indications included hydrocephalus (20%, 37/189), tumor (15%, 29/189), posterior fossa decompression (14%, 26/189), traumatic brain injury (11%, 20/189), bypass (27%, 52/189), intracerebral hemorrhage (4%, 7/189), ischemic stroke (3%, 5/189), aneurysm and subarachnoid hemorrhage (3%, 5/189), subdural hematoma (2%, 4/189), and vasculitis and other bone revisions (2%, 4/189). Complications described in the entire cohort included revision or delayed scalp healing (3%, 6/189), wound infection (3%, 5/189), epidural hematoma (2%, 3/189), cerebrospinal fluid leaks (1%, 2/189), new seizure (1%, 2/189), and oncologic relapse with subsequent prosthesis removal (<1%, 1/189). Most studies utilized linear or phased array ultrasound transducers at 3-12 MHz. Sources of artifact on sonographic imaging included prosthesis curvature, pneumocephalus, plating system, and dural sealant. Reported findings were mainly qualitative. We, therefore, suggest that future studies should collect quantitative measurement data during transcranioplasty ultrasonography to validate imaging techniques.

Trends and In-Hospital Outcomes in Patients with Vocal Fold Paralysis after Ischemic and Intracerebral Hemorrhagic Stroke: A Propensity Matched 20-Year Analysis of the Nationwide Inpatient Sample.

OBJECTIVE: Laryngeal manifestations of stroke have been sparsely described in the literature, specifically vocal fold paralysis (VFP). This study aimed to identify the prevalence, characteristics, and in-hospital outcomes of patients presenting with VFP after acute ischemic stroke (AIS) and intracranial hemorrhage (ICH). METHODS: A query of the 2000-2019 Nationwide Inpatient Sample was performed for patients admitted with AIS (International Classification of Diseases, Ninth Revision 433, 43,401, 43,411, 43,491, International Classification of Diseases, Tenth Revision I63) and ICH (International Classification of Diseases, Ninth Revision 431, 432.9, International Classification of Diseases, Tenth Revision I61, I62.9). Demographics, comorbidities, and outcomes were identified. Univariate analysis with t-tests or χ2 performed as appropriate. A 1:1 nearest neighbor propensity score matched cohort was generated. Variables with standardized mean differences > 0.1 used in multivariable regression to generate adjusted odds ratios (AOR)/ß-coefficients for VFP on outcomes. Significance was set at an alpha level of < 0.001. All analysis were performed in R version 4.1.3. RESULTS: A total of 10,415,286 patients with AIS were included; 11,328 (0.1%) had VFP. Of 2,000,868 patients with ICH 2132 (0.1%) had in-hospital VFP. Multivariable analysis revealed that patients with VFP after AIS were less likely to be discharged home (AOR 0.32; 95% confidence interval {CI}: 0.18-0.57; P < 0.001) and elevated total hospital charges (ß coefficient = 59,684.6; 95% CI = 18,365.12-101,004.07; P = 0.005). Patients with VFP after ICH were less likely to experience in-hospital mortality (AOR 0.53; 95% CI: 0.34-0.79; P = 0.002) with longer hospital stays (1.99 days; 95% CI: 1.78-2.21; P < 0.001) and elevated total hospital charges (ß coefficient = 53,905.35; 95% CI = 16,352.84-91,457.85; P = 0.005).. CONCLUSIONS: VFP in patients with ischemic stroke and ICH; although an infrequent complication is associated with functional impairment, longer hospital stay, and higher charges.

Preoperative cerebral angiography nearly doubles the rate of diffusion-weighted imaging lesion detection following minimally invasive surgery for intracerebral hemorrhage.

BACKGROUND: Diffusion-weighted imaging (DWI) lesions have been linked to poor outcomes after intracerebral hemorrhage (ICH). We aimed to assess the impact of cerebral digital subtraction angiography (DSA) on the presence of DWI lesions in patients who underwent minimally invasive surgery (MIS) for ICH. METHODS: Retrospective chart review was performed on ICH patients treated with MIS in a single health system from 2015 to 2021. One hundred and seventy consecutive patients who underwent postoperative MRIs were reviewed. Univariate analyses were conducted to determine associations. Variables with p<0.05 were included in multivariate analyses. RESULTS: DWI lesions were present in 88 (52%) patients who underwent MIS for ICH. Of the 83 patients who underwent preoperative DSA, 56 (67%) patients demonstrated DWI lesions. In this DSA cohort, older age, severe leukoaraiosis, larger preoperative hematoma volume, and increased presenting National Institutes of Health Stroke Score (NIHSS) were independently associated with DWI lesion identification (p<0.05). In contrast, of 87 patients who did not undergo DSA, 32 (37%) patients demonstrated DWI lesions on MRI. In the non-DSA cohort, presenting systolic blood pressure, intraventricular hemorrhage, and NIHSS were independently associated with DWI lesions (p<0.05). Higher DWI lesion burden was independently associated with poor modified Rankin Scale (mRS) at 6 months on a univariate (p=0.02) and multivariate level (p=0.02). CONCLUSIONS: In this cohort of ICH patients who underwent minimally invasive evacuation, preprocedural angiography was associated with the presence of DWI lesions on post-ICH evacuation MRI. Furthermore, the burden of DWI lesions portends a worse prognosis after ICH.

External Ventricular Drain Training in Medical Students Improves Procedural Accuracy and Attitudes Toward Virtual Reality.

OBJECTIVE: Neurosurgery residents face a learning curve at the beginning of residency. Virtual reality (VR) training may alleviate challenges through an accessible, reusable, anatomical model. METHODS: Medical students performed external ventricular drain placements in VR to characterize the learning curve from novice to proficient. Distance from catheter to foramen of Monro and location with respect to ventricle were recorded. Changes in attitudes toward VR were assessed. Neurosurgery residents performed external ventricular drain placements to validate proficiency benchmarks. Resident and student impressions of the VR model were compared. RESULTS: Twenty-one students with no neurosurgical experience and 8 neurosurgery residents participated. Student performance improved significantly from trial 1 to 3 (15 mm [12.1-20.70] vs. 9.7 [5.8-15.3], P = 0.02). Student attitudes regarding VR utility improved significantly posttrial. The distance to foramen of Monro was significantly shorter for residents than for students in trial 1 (9.05 [8.25-10.73] vs. 15 [12.1-20.70], P = 0.007) and trial 2 (7.45 [6.43-8.3] vs. 19.5 [10.9-27.6], P = 0.002). By trial 3 there was no significant difference (10.1 [8.63-10.95 vs. 9.7 [5.8-15.3], P = 0.62). Residents and students provided similarly positive feedback for VR in resident curricula, patient consent, preoperative practice and planning. Residents provided more neutral-to-negative feedback regarding skill development, model fidelity, instrument movement, and haptic feedback. CONCLUSIONS: Students showed significant improvement in procedural efficacy which may simulate resident experiential learning. Improvements in fidelity are needed before VR can become a preferred training technique in neurosurgery.

Contralesional angiotensin type 2 receptor activation contributes to recovery in experimental stroke.

We and others have previously shown that angiotensin II receptor type 2 receptor (AT2R) is upregulated in the contralesional hemisphere after stroke in normoglycemic Wistar rats. In this study, we examined the expression of AT2R in type 2 diabetic Goto-Kakizaki (GK) rats and control Wistars after stroke. We also tested the contribution of the contralesional AT2R in recovery after stroke through a specific knockdown of the AT2R in this hemisphere only. Two experiments were conducted. In the first experiment, GK rats were subjected to middle cerebral artery occlusion (MCAO) and treated with the angiotensin II receptor type 1 receptor (AT1R) blocker candesartan or saline at reperfusion. Stroke outcomes, as well as AT2R expression, were examined and compared to control Wistars at 24 h. In the second experiment, localized AT2R knockdown was achieved through intrastriatal injection of short hairpin RNA (shRNA) lentiviral particles or non-targeting control into the left-brain hemisphere of Wistar rats. After 14 days, rats were subjected to right MCAO and treated with the AT2R agonist, Compound 21 (C21), or saline for 7 days. Behavioral outcomes were assessed for up to 10 days. In the first experiment, stroke reduced the expression of AT2R in GK rats. Candesartan treatment failed to improve the neurobehavioral outcomes, preserve vascular integrity or reduce oxidative/nitrative stress or apoptotic markers at 24 h post stroke in these animals. In the second experiment, contralesional AT2R knockdown reduced the C21-mediated functional recovery after stroke. In conclusion, contralesional AT2R upregulation after stroke is blunted in diabetic rats which show reduced sensitivity to post-stroke candesartan treatment. Contralesional AT2R could be involved in C21-mediated functional recovery after stroke.

Time from image acquisition to endovascular team notification: a new target for enhancing acute stroke workflow.

OBJECTIVE: To quantify the time between initial image acquisition (CT angiography (CTA)) and notification of the neuroendovascular surgery (NES) team, a potentially high yield time window to target for optimization of endovascular thrombectomy (ET) treatment times. METHODS: We reviewed our multihospital database for all patients with a stroke with emergent large vessel occlusion treated with ET between January 1, 2017 and August 5, 2020. We dichotomized patients into rapid (≤20 min) and delayed (>20 min) notification times and analyzed treatment characteristics and outcomes. RESULTS: Of 367 patients with ELVO undergoing ET for whom notification data were available, the median time from CTA to NES team notification was 24 min (IQR 12-47). The median total treatment time was 180 min (IQR 129-252). The median times from CTA to NES team notification for rapid (n=163) and delayed (n=204) cohorts were 11 (IQR 6-15) and 43 (IQR 30-80) min, respectively (p<0.001). The median overall times to reperfusion were 134 min (IQR 103-179) and 213 min (IQR 172-291), respectively (p<0.001). The delayed patients had a significantly lower National Institutes of Health Stroke Scale (NIHSS) score on presentation (15 (IQR 9-20) vs 16 (IQR 11-22), p=0.03), were younger (70 (IQR 60-79) vs 77 (IQR 64-85), p<0.001), and more often presented with posterior circulation occlusion (16.7% vs 7.4%, p<0.01). The group with rapid notification time had a statistically larger median improvement in NIHSS score from admission to discharge (6 (IQR 0.5-14) vs 5 (IQR 0.5-10), p=0.04). CONCLUSIONS: Time delays from initial CTA acquisition to NES team notification can prevent expedient treatment with ET. Process improvements and automated stroke detection on imaging with automated notification of the NES team may ultimately improve time to reperfusion.

Trials in thrombectomy for acute ischemic stroke: Describing the state of clinical research in the field.

BACKGROUND: Endovascular thrombectomy has revolutionized treatment of ischemic stroke. Given the clinical and socioeconomic support for thrombectomy, new devices, procedures, and pharmaceuticals have emerged in recent years, and have been subject to a growing number of clinical trials worldwide. OBJECTIVE: To define the current state of thrombectomy clinical trials, highlight recent trends, and help guide future research in this area. METHODS: Current and previous clinical trials involving thrombectomy for ischemic stroke were queried from the Clinicaltrials.gov database. Trials were categorized by their current status, study design, funding type, exclusion criteria, study phase, enrollment, start and completion dates, country of origin, item of investigation, outcome metrics, and whether a peer-reviewed publication was linked to the trial. RESULTS: Querying the ClinicalTrials.gov registry yielded 196 trials, of which 161 (82.1 %) were started within the past 5 years. The average time to completion was 30.6 months. A total of 62 studies (31.6 %) examined the safety or efficacy of a thrombectomy device, 29 (14.8 %) investigated a pharmacological intervention alone or in combination with a device, 59 (30.1 %) examined aspects of the endovascular procedure on patient outcomes, and 14 (7.2 %) examined diagnostic utility during thrombectomy. Most trials were funded by academic centers (53.1 %) or industry (34.7 %). Although the United States contributed the most studies overall (59; 30.1 %), studies from European and Asian countries have been increasing since 2015. CONCLUSION: These trends indicate an increasing number of trials starting the past few years, with most occurring in Europe and examining devices or aspects of the thrombectomy procedure.

Endovascular Therapy Versus Microsurgical Clipping of Ruptured Wide Neck Aneurysms (EVERRUN Registry): a multicenter, prospective propensity score analysis.

OBJECTIVE: Randomized controlled trials have demonstrated the superiority of endovascular therapy (EVT) compared to microsurgery (MS) for ruptured aneurysms suitable for treatment or when therapy is broadly offered to all presenting aneurysms; however, wide neck aneurysms (WNAs) are a challenging subset that require more advanced techniques and warrant further investigation. Herein, the authors sought to investigate a prospective, multicenter WNA registry using rigorous outcome assessments and compare EVT and MS using propensity score analysis (PSA). METHODS: Untreated, ruptured, saccular WNAs were included in the analysis. A WNA was defined as having a neck ≥ 4 mm or a dome/neck ratio (DNR) < 2. The primary outcome was the modified Rankin Scale (mRS) score at 1 year posttreatment, as assessed by blinded research nurses (good outcome: mRS scores 0-2) and compared using PSA. RESULTS: The analysis included 87 ruptured aneurysms: 55 in the EVT cohort and 32 in the MS cohort. Demographics were similar in the two cohorts, including Hunt and Hess grade (p = 0.144) and modified Fisher grade (p = 0.475). WNA type inclusion criteria were similar in the two cohorts, with the most common type having a DNR < 2 (EVT 60.0% vs MS 62.5%). More anterior communicating artery aneurysms (27.3% vs 18.8%) and posterior circulation aneurysms (18.2% vs 0.0%) were treated with EVT, whereas more middle cerebral artery aneurysms were treated with MS (34.4% vs 18.2%, p = 0.025). Within the EVT cohort, 43.6% underwent stand-alone coiling, 50.9% balloon-assisted coiling, 3.6% stent-assisted coiling, and 1.8% flow diversion. The 1-year mRS score was assessed in 81 patients (93.1%), and the primary outcome demonstrated no increased risk for a poor outcome with MS compared to EVT (OR 0.43, 95% CI 0.13-1.45, p = 0.177). The durability of MS was higher, as evidenced by retreatment rates of 12.7% and 0% for EVT and MS, respectively (p = 0.04). CONCLUSIONS: EVT and MS had similar clinical outcomes at 1 year following ruptured WNA treatment. Because of their challenging anatomy, WNAs may represent a population in which EVT's previously demonstrated superiority for ruptured aneurysm treatment is less relevant. Further investigation into the treatment of ruptured WNAs is warranted.