Vestibular Schwannoma International Study of Active Surveillance Versus Stereotactic Radiosurgery: The VISAS Study.

PURPOSE: The present study assesses the safety and efficacy of stereotactic radiosurgery (SRS) versus observation for Koos grade 1 and 2 vestibular schwannoma (VS), benign tumors affecting hearing and neurological function. METHODS AND MATERIALS: This multicenter study analyzed data from Koos grade 1 and 2 VS patients managed with SRS (SRS group) or observation (observation group). Propensity score matching balanced patient demographics, tumor volume, and audiometry. Outcomes measured were tumor control, serviceable hearing preservation, and neurological outcomes. RESULTS: In 125 matched patients in each group with a 36-month median follow-up (P = .49), SRS yielded superior 5- and 10-year tumor control rates (99% CI, 97.1%-100%, and 91.9% CI, 79.4%-100%) versus observation (45.8% CI, 36.8%-57.2%, and 22% CI, 13.2%-36.7%; P < .001). Serviceable hearing preservation rates at 5 and 9 years were comparable (SRS 60.4% CI, 49.9%-73%, vs observation 51.4% CI, 41.3%-63.9%, and SRS 27% CI, 14.5%-50.5%, vs observation 30% CI, 17.2%-52.2%; P = .53). SRS were associated with lower odds of tinnitus (OR = 0.39, P = .01), vestibular dysfunction (OR = 0.11, P = .004), and any cranial nerve palsy (OR = 0.36, P = .003), with no change in cranial nerves 5 or 7 (P > .05). Composite endpoints of tumor progression and/or any of the previous outcomes showed significant lower odds associated with SRS compared with observation alone (P < .001). CONCLUSIONS: SRS management in matched cohorts of Koos grade 1 and 2 VS patients demonstrated superior tumor control, comparable hearing preservation rates, and significantly lower odds of experiencing neurological deficits. These findings delineate the safety and efficacy of SRS in the management of this patient population.

Frailty is a Predictor of Increased Readmissions and Increased Postoperative Complications After Elective Treatment of Unruptured Aneurysms.

INTRODUCTION: Frailty is a state of decreased physiologic reserve associated with adverse treatment outcomes across surgical specialties. We sought to determine whether frailty affected patient outcomes after elective treatment (open microsurgical clipping or endovascular therapy [EVT]) of unruptured cerebral aneurysms (UCAs). METHODS: The National Readmissions Database was queried from 2010 to 2014 to identify patients who had a known UCA and underwent elective clipping or EVT. Frailty was assessed using the Johns Hopkins Adjusted Clinical Groups frailty indicator tool. Multivariable exact logistic regression analyses were conducted to assess the associations between frailty and the primary outcome variables of 30- and 90-day readmissions, complications, length of stay (LOS), and patient disposition. RESULTS: Of 18,483 patients who underwent elective treatment for UCAs, 358 (1.9%) met the criteria for frailty. After adjusting for patient- and hospital-based factors, frailty (30-day: odds ratio [OR], 1.55; 95% confidence interval [CI], 1.11-2.17; P = 0.01; 90-day: OR, 1.47; 95% CI, 1.05-2.06; P = 0.02) and clipping versus EVT (30-day: OR, 2.12; 95% CI, 1.85-2.43; P < 0.000; 90-day: OR, 1.80; 95% CI, 1.59-2.03; P < 0.0001) were associated with increased readmission rates. Furthermore, frailty was associated with an increased rate of complications (surgical: OR, 2.91; 95% CI, 2.27-3.72; P < 0.0001; neurological: OR, 3.04; 95% CI, 2.43-3.81; P < 0.0001; major: OR, 2.75; 95% CI, 1.96-3.84; P < 0.0001), increased LOSs (incidence rate ratio, 3.08; 95% CI, 2.59-3.66; P < 0.0001), and an increased rate of nonroutine disposition (OR, 3.94; 95% CI, 2.91-5.34; P < 0.0001). CONCLUSIONS: Frailty was associated with an increased likelihood of 30- and 90-day readmissions after elective treatment of UCAs. Frailty was notably associated with several postoperative complications, longer LOSs, and nonroutine disposition in the treatment of UCAs.

Surgical Outcomes Following Vestibular Schwannoma Resection in Patients over the Age of Sixty-five.

Objective Vestibular schwannoma (VS) are benign, often slow growing neoplasms. Some institutions opt for radiosurgery in symptomatic patients of advanced age versus surgical resection. The aim of the study is to analyze surgical outcomes of VS in patients over the age of 65 who were either not candidates for or refused radiosurgery. Methods This includes retrospective analysis of VS patients between 1988 and 2020. Demographics, tumor characteristics, surgical records, and clinical outcomes were recorded. Patient preference for surgery over radiosurgery was recorded in the event that patients were offered both. Facial nerve outcomes were quantified using House-Brackmann (HB) scores. Tumor growth was defined by increase in size of >2 mm. Results In total, 64 patients were included of average age 72.4 years (65-84 years). Average maximum tumor diameter was 29 mm (13-55 mm). Forty-five patients were offered surgery or GKRS, and chose surgery commonly due to radiation aversion (48.4%). Gross total resection was achieved in 39.1% ( n = 25), near total 32.8% ( n = 21), and subtotal 28.1% ( n = 18). Average hospitalization was 5 days [2-17] with 75% ( n = 48) discharged home. Postoperative HB scores were good (HB1-2) in 43.8%, moderate (HB3-4) in 32.8%, and poor (HB5-6) in 23.4%. HB scores improved to good in 51.6%, moderate in 31.3%, and remained poor in 17.1%, marking a rate of facial nerve improvement of 10.9%. Tumor control was achieved in 95.3% of cases at an average follow-up time of 37.8 months. Conclusion VS resection can be safely performed in patients over the age of 65. Advanced age should not preclude a symptomatic VS patient from being considered for surgical resection.

A Review of Medical and Surgical Options for the Treatment of Facial Pain.

Facial pain is a common medical complaint that is easily misdiagnosed. As a result, this pain often goes mistreated. Despite this, there are a variety of pharmacologic, surgical, and neuromodulatory options for the treatment of facial pain. In this review, the authors detail the forms of facial pain and their treatment options. They discuss the common medications used in the first-line treatment of facial pain and the second-line surgical and neuromodulatory options available to patients when pharmacologic options fail.

Minocycline decreases blood-brain barrier permeability following aneurysmal subarachnoid hemorrhage: a randomized, double-blind, controlled trial.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH)-induced vasospasm is linked to increased inflammatory cell trafficking across a permeable blood-brain barrier (BBB). Elevations in serum levels of matrix metalloprotease 9 (MMP9), a BBB structural protein, have been implicated in the pathogenesis of vasospasm onset. Minocycline is a potent inhibitor of MMP9. The authors sought to detect an effect of minocycline on BBB permeability following aSAH. METHODS: Patients presenting within 24 hours of symptom onset with imaging confirmed aSAH (Fisher grade 3 or 4) were randomized to high-dose (10 mg/kg) minocycline or placebo. The primary outcome of interest was BBB permeability as quantitated by contrast signal intensity ratios in vascular regions of interest on postbleed day (PBD) 5 magnetic resonance permeability imaging. Secondary outcomes included serum MMP9 levels and radiographic and clinical evidence of vasospasm. RESULTS: A total of 11 patients were randomized to minocycline (n = 6) or control (n = 5) groups. No adverse events or complications attributable to minocycline were reported. High-dose minocycline administration was associated with significantly lower permeability indices on imaging analysis (p < 0.01). There was no significant difference with respect to serum MMP9 levels between groups, although concentrations trended upward in both cohorts. Radiographic vasospasm was noted in 6 patients (minocycline = 3, control = 3), with only 1 patient developing symptoms of clinical vasospasm in the minocycline cohort. There was no difference between cohorts with respect to Lindegaard ratios, transcranial Doppler values, or onset of vasospasm. CONCLUSIONS: Minocycline at high doses is well tolerated in the ruptured cerebral aneurysm population. Minocycline curtails breakdown of the BBB following aSAH as evidenced by lower permeability indices, though minocycline did not significantly alter serum MMP9 levels. Larger randomized clinical trials are needed to assess minocycline as a neuroprotectant against aSAH-induced vasospasm. Clinical trial registration no.: NCT04876638 (clinicaltrials.gov).

Neurosurgery residency and fellowship education in the United States: 2 decades of system development by the One Neurosurgery Summit organizations.

The purpose of this report is to chronicle a 2-decade period of educational innovation and improvement, as well as governance reform, across the specialty of neurological surgery. Neurological surgery educational and professional governance systems have evolved substantially over the past 2 decades with the goal of improving training outcomes, patient safety, and the quality of US neurosurgical care. Innovations during this period have included the following: creating a consensus national curriculum; standardizing the length and structure of neurosurgical training; introducing educational outcomes milestones and required case minimums; establishing national skills, safety, and professionalism courses; systematically accrediting subspecialty fellowships; expanding professional development for educators; promoting training in research; and coordinating policy and strategy through the cooperation of national stakeholder organizations. A series of education summits held between 2007 and 2009 restructured some aspects of neurosurgical residency training. Since 2010, ongoing meetings of the One Neurosurgery Summit have provided strategic coordination for specialty definition, neurosurgical education, public policy, and governance. The Summit now includes leadership representatives from the Society of Neurological Surgeons, the American Association of Neurological Surgeons, the Congress of Neurological Surgeons, the American Board of Neurological Surgery, the Review Committee for Neurological Surgery of the Accreditation Council for Graduate Medical Education, the American Academy of Neurological Surgery, and the AANS/CNS Joint Washington Committee. Together, these organizations have increased the effectiveness and efficiency of the specialty of neurosurgery in advancing educational best practices, aligning policymaking, and coordinating strategic planning in order to meet the highest standards of professionalism and promote public health.

Preexisting Ventricular Shunts Are Associated with Failed Evacuation of Acute Subdural Hematomas: Single-Institution Case Series of Complications and Management Strategies.

BACKGROUND: The effect of ventricular shunts on radiographic outcomes after evacuation of acute subdural hematomas (aSDHs) has not yet been established. We studied a series of patients who had undergone craniotomy for aSDH, exploring a possible relationship between the occurrence of a postoperative extra-axial collection (EAC) and the presence of a ventricular shunt. METHODS: We reviewed all craniotomies for convexity aSDH performed between July 2015 and June 2020. The medical record review included perioperative coagulation studies, platelet counts, and antiplatelet and anticoagulation agent use. Univariate and multivariate analyses were conducted to identify the factors associated with postoperative EACs and reevacuation. RESULTS: A total of 58 patients had undergone craniotomy for aSDHs, including 9 with ventricular shunts. The median age was 67 years (interquartile range, 54-78 years), and 40% of the patients were women. Of the 58 patients, 16 were taking antiplatelet agents, and 6 were taking anticoagulation agents. Ten patients had developed perioperative thrombocytopenia (platelet count, <100,000/µL). Twelve patients had perioperative coagulopathy (international normalized ratio, ≥1.5). A postoperative EAC >10 mm occurred in 17 patients (29.3%). Eight patients (13.8%) had undergone reevacuation. The presence of a shunt and an increasing preoperative aSDH size were independently associated with an EAC >10 mm (P = 0.013 and P = 0.003, respectively). Only the presence of a shunt predicted for the need for reevacuation (P = 0.001). The shunts were explanted (n = 3) or valves were adjusted (n = 3) in all but 3 cases. CONCLUSIONS: We found that a lack of brain reexpansion after aSDH evacuation worsens radiographic outcomes and was more common in patients with shunts. Increasing shunt valve resistance might help prevent the formation of large EACs after aSDH evacuation.

Readmissions after ventricular shunting in pediatric patients with hydrocephalus: a Nationwide Readmissions Database analysis.

OBJECTIVE: Cerebrospinal fluid diversion via ventricular shunting is a common surgical treatment for hydrocephalus in the pediatric population. No longitudinal follow-up data for a multistate population-based cohort of pediatric patients undergoing ventricular shunting in the United States have been published. In the current review of a nationwide population-based data set, the authors aimed to assess rates of shunt failure and hospital readmission in pediatric patients undergoing new ventricular shunt placement. They also review patient- and hospital-level factors associated with shunt failure and readmission. METHODS: Included in this study was a population-based sample of pediatric patients with hydrocephalus who, in 2010-2014, had undergone new ventricular shunt placement and had sufficient follow-up, as recorded in the Nationwide Readmissions Database. The authors analyzed the rate of revision within 6 months, readmission rates at 30 and 90 days, and potential factors associated with shunt failure including patient- and hospital-level variables and type of hydrocephalus. RESULTS: A total of 3520 pediatric patients had undergone initial ventriculoperitoneal shunt placement for hydrocephalus at an index admission. Twenty percent of these patients underwent shunt revision within 6 months. The median time to revision was 44.5 days. Eighteen percent of the patients were readmitted within 30 days and 31% were readmitted within 90 days. Different-hospital readmissions were rare, occurring in ≤ 6% of readmissions. Increased hospital volume was not protective against readmission or shunt revision. Patients with grade 3 or 4 intraventricular hemorrhage were more likely to have shunt malfunctions. Patients who had private insurance and who were treated at a large hospital were less likely to be readmitted. CONCLUSIONS: In a nationwide, population-based database with longitudinal follow-up, shunt failure and readmission were common. Although patient and hospital factors were associated with readmission and shunt failure, system-wide phenomena such as insufficient centralization of care and fragmentation of care were not observed. Efforts to reduce readmissions in pediatric patients undergoing ventricular shunt procedures should focus on coordinating care in patients with complex neurological diseases and on reducing healthcare disparities associated with readmission.

Utilization of Discarded Surgical Tissue from Ultrasonic Aspirators to Establish Patient-Derived Metastatic Brain Tumor Cells: A Guide from the Operating Room to the Research Laboratory.

Patient-derived cells from surgical resections are of paramount importance to brain tumor research. It is well known that there is cellular and microenvironmental heterogeneity within a single tumor mass. Thus, current established protocols for propagating tumor cells in vitro are limiting because resections obtained from conventional singular samples limit the diversity in cell populations and do not accurately model the heterogeneous tumor. Utilization of discarded tissue obtained from cavitron ultrasonic surgical aspirator (CUSA) of the whole tumor mass allows for establishing novel cell lines in vitro from the entirety of the tumor, thereby creating an accurate representation of the heterogeneous population of cells originally present in the tumor. Furthermore, while others have described protocols for establishing patient tumor lines once tissue has arrived in the research lab, a primer from the operating room (OR) to the research lab has not been described before. This is integral, as basic research scientists need to understand the surgical environment of the OR, including the methods utilized to obtain a patient's tumor resection, in order to more accurately model cancer biology in laboratory. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Establishment of brain tumor cell lines from patient-derived CUSA samples: processing brain tumor sample from the OR to the lab Support Protocol 1: Sterilization of microsurgical tools in preparation for dissection Support Protocol 2: Collagen coating of tissue culture flasks Basic Protocol 2: Selection of tumor cells in vitro Support Protocol 3: FACS sorting tumor sample to isolate cancer cells from heterogeneous cell population.

Neuroprotective effect of minocycline against acute brain injury in clinical practice: A systematic review.

Acute brain injury is a leading cause of morbidity and mortality worldwide. The term is inclusive of traumatic brain injury, cerebral ischemia, subarachnoid hemorrhage, and intracerebral hemorrhage. Current pharmacologic treatments have had minimal effect on improving neurological outcomes leading to a significant interest in the development neuroprotective agents. Minocycline is a second-generation tetracycline with high blood brain barrier penetrance due to its lipophilic properties. It functions across multiple molecular pathways involved in secondary-injury cascades following acute brain injury. Animal model studies suggest that minocycline might lead to improved neurologic outcomes, but few such trials exist in humans. Clinical investigations have been limited to small randomized trials in ischemic stroke patients which have not demonstrated a clear advantage in neurologic outcomes, but also have not been sufficiently powered to draw definitive conclusions. The potential neuroprotective effect of minocycline in the setting of traumatic brain injury, subarachnoid hemorrhage, and intracerebral hemorrhage have all been limited to pilot studies with phase II/III investigations pending. The authors aim to synthesize what is currently known about minocycline as a neuroprotective agent against acute brain injury in humans.

Tracking Scan to Incision Time in Patients with Emergent Operative Traumatic Brain Injuries as a Measure for Systems-Based Practice in Neurosurgical Trainees.

BACKGROUND: Evaluation of trainee performance remains a challenge in resident education, particularly for systems-based practice (SysBP) metrics including care coordination and interdisciplinary teamwork. Time to intervention is an important modifiable outcome variable in severe traumatic brain injury (TBI) and may serve as a trackable metric for SysBP evaluation. METHODS: We retrospectively studied time from computed tomography head scan to surgical incision (CTH-INC, minutes) among neurosurgical trainees treating patients with emergently operative TBI as a proxy SysBP measure. Our institutional operative database was utilized to identify all emergent TBI cases between July 2015 and June 2020. Patients evaluated by program year (PGY)-2 residents proceeding directly to the operating room from the emergency department were included. Statistical analysis was performed using linear regression. RESULTS: One hundred sixty-six cases triaged by 14 PGY-2 neurosurgical trainees were analyzed. Median CTH-INC was 104 minutes (interquartile range, 82-136 minutes). CTH-INC improved 20.1% over the academic year (95% confidence interval, 4.3%-33.2%, P = 0.015). Between the first and second 6-month periods, the rate of CTH-INC within 90 minutes (29% vs. 46%, P = 0.04) improved. On a per-individual PGY-2 basis, median CTH-INC ranged from 83-127 minutes, 25th percentile CTH-INC ranged from 62-108 minutes, and fastest CTH-INC ranged from 45-92 minutes. CONCLUSIONS: CTH-INC is an objective and trackable proxy measure for evaluating SysBP during neurosurgical training. Use of CTH-INC or other time metrics in resident evaluations should not supersede the safe and effective delivery of patient care.

Risk Factors for Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage: A Population-Based Study of 8346 Patients.

BACKGROUND: A recent systematic review and meta-analysis found that there was a lack of consensus regarding risk factors for cerebral vasospasm in aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE: To identify risk factors associated with increased likelihood of cerebral vasospasm after aSAH using the largest, all-payer, inpatient database in the United States. METHODS: The Nationwide Readmissions Database (2016) was queried using International Classification of Diseases, Tenth Revision codes to identify patients (age ≥18 years) treated (coiling or clipping) for aSAH. Exposure variables included demographics, comorbidities, location and clinical grade of aSAH, treatment type, and laboratory anomalies. Multivariable analysis was conducted to identify factors independently associated with cerebral vasospasm (ICD-10 code I67.84). RESULTS: The rate of vasospasm was 28.1% in 8346 patients with treated aSAH. In multivariable analysis, vasospasm risk was inversely proportional to age (P < 0.001). Substance abuse, particularly tobacco smoking and cocaine, was associated with vasospasm (P < 0.05). Advanced SAH severity (Hunt and Hess grade ≥2) approximately doubled risk of vasospasm (P < 0.001). Poor hemodynamic status, including anemia (odds ratio [OR], 1.8), hypovolemia (OR, 1.6), and hypotension (OR, 1.4), was correlated with vasospasm. Laboratory abnormalities, including leukocytosis (OR, 1.3), hyponatremia (OR, 1.4), and hypokalemia (OR, 1.3), were associated with vasospasm (all P < 0.05). CONCLUSIONS: In the first nationwide analysis of cerebral vasospasm, risk factors included younger age, female sex, smoking history, hemodynamic compromise, and clinical severity of aSAH. Recently proposed biomarkers, including leukocytosis and hypokalemia, were supported by our findings. This study may assist risk stratification and earlier detection of vasospasm.

Rate of Intracranial Hemorrhage After Minor Head Injury.

INTRODUCTION: Computed tomography scans of the head (CTH) are an important component of the initial patient evaluation after blunt head trauma in select patients. Here we review findings of CTH performed for mild traumatic brain injury (TBI) at a Level I trauma center over a two-year period. We subsequently discuss the role and limitations of published clinical decision rules aiming to decrease unnecessary CTH in mild TBI patients. METHODS: We reviewed all Emergency Department CTH obtained after blunt head trauma between 2010 and 2011. Patient demographics and radiology report texts were collected. Reports were cross-referenced with our institutional trauma database to obtain initial Glasgow Coma Scale (GCS). Mild TBI was defined by an initial GCS 13-15 with or without loss of consciousness or post-traumatic amnesia. RESULTS: There were 5,634 mild TBI patients evaluated with CTH. A total of 477 scans (8.5%) were positive for intracranial hemorrhage. Of these, 188 (39.4%) showed more than one type of intracranial hemorrhage. The most common findings were subdural hematomas (262, 4.7% of scans), traumatic subarachnoid hemorrhages (252, 4.5% of scans), and cerebral contusions/intraparenchymal hematomas (212, 3.8% of scans). Older age (p<0.001) and male gender (p<0.001) were associated with positive CTH. CONCLUSIONS: The rate of positive CTH in mild TBI patients in our population falls within a historical range. The clinical and medicolegal implications of missed intracranial hemorrhage have remained important factors limiting the implementation of clinical decision rules in screening mild TBI patients for CTH.

Epigenetic modulator inhibition overcomes temozolomide chemoresistance and antagonizes tumor recurrence of glioblastoma.

Glioblastoma multiforme (GBM) heterogeneity causes a greater number of deaths than any other brain tumor, despite the availability of alkylating chemotherapy. GBM stem-like cells (GSCs) contribute to GBM complexity and chemoresistance, but it remains challenging to identify and target GSCs or factors that control their activity. Here, we identified a specific GSC subset and show that activity of these cells is positively regulated by stabilization of methyl CpG binding domain 3 (MBD3) protein. MBD3 binds to CK1A and to BTRCP E3 ubiquitin ligase, triggering MBD3 degradation, suggesting that modulating this circuit could antagonize GBM recurrence. Accordingly, xenograft mice treated with the CK1A activator pyrvinium pamoate (Pyr-Pam) showed enhanced MBD3 degradation in cells expressing high levels of O6-methylguanine-DNA methyltransferase (MGMT) and in GSCs, overcoming temozolomide chemoresistance. Pyr-Pam blocked recruitment of MBD3 and the repressive nucleosome remodeling and deacetylase (NuRD) complex to neurogenesis-associated gene loci and increased acetyl-histone H3 activity and GSC differentiation. We conclude that CK1A/BTRCP/MBD3/NuRD signaling modulates GSC activation and malignancy, and that targeting this signaling could suppress GSC proliferation and GBM recurrence.

Readmission with venous thromboembolism after surgical treatment by primary cancer site.

BACKGROUND: Venous thromboembolism (VTE) is a common, high-mortality condition among surgical cancer patients. Comprehensive analyses of VTE among postoperative cancer patients are lacking. We sought to determine the association between readmission with VTE and primary cancer diagnosis in a nationwide database at 90- and 180-days after initial admission for cancer surgery. METHODS: Retrospective analyses of post-surgical cancer patients readmitted with VTE were conducted using data from the Nationwide Readmissions Database (NRD) (2010-2014). Multivariate logistic regression models adjusting for patient and hospital factors were used to determine 90- and 180-day readmission rates for VTE by cancer type. Patient factors associated with readmission were also examined. RESULTS: Among a sample of 535,992 cancer patients undergoing tumor resection, readmission with VTE occurred in 1.7% within 90-days and 2.3% within 180-days. Patients readmitted for VTE experienced a 7% mortality rate. Highest rates of VTE readmission at 180 days occurred in brain (6.7%), pancreatic (5.6%), and respiratory and intrathoracic cancers (4.4%). Using pancreatic cancer as reference, brain cancer had the highest odds of readmission at 180-days (OR 2.23, 95% CI [1.95-2.55]). CONCLUSION: Readmission with VTE among surgical cancer patients occurred in 2.3% of patients within 180 days. Among cancer types, primary brain cancer was independently associated with readmission with VTE.

Comorbid depression associated with non-routine discharge following craniotomy for low-grade gliomas and benign tumors - a nationwide readmission database analysis.

PURPOSE: Prior studies have demonstrated elevated rates of depression in patients with malignant brain tumor; however, the prevalence and effect on surgical outcomes in patients with low-grade gliomas (LGG) and benign brain tumors (BBT) remain unknown. Readmission and non-routine discharge, which includes discharge to skilled nursing, rehabilitative, and other inpatient facilities, are well-established quality of care indicators. We sought to analyze the association between comorbid depression and non-routine discharge, readmission, and other post-operative inpatient outcomes in patients with LGG and BBT. METHODS: The Nationwide Readmissions Database from 2010 to 2014 was retrospectively queried to select for surgically treated patients with LGG and BBT. Multivariable logistic regression models adjusting for patient and hospital characteristics were used to determine the effects of comorbid depression on post-operative outcomes. Interaction of gender and depression on non-routine disposition was analyzed. RESULTS: We identified 31,654 craniotomies for resection of BBT and LGG (2010-2014). The majority of patients (64.1%) were female. The rate of depression comorbid with BBT and LGG was 11.9%. Depression was associated with non-routine discharge after surgery (OR 1.19, p 0.0002*), but was not associated with increased morbidity, mortality, or readmission at 30 or 90 days. The rate of comorbid depression was higher among female than male patients (14.0 vs. 8.0%). Depression in males was associated with a 38% increased likelihood of non-routine disposition (p = 0.0002*), while depression in females was associated with a 13% increased likelihood of non-routine disposition (p = 0.03*). CONCLUSION: Depression is prevalent in patients with LGG and BBT and is associated with increased risk of non-routine discharge following surgical intervention. The increased likelihood of non-routine disposition is greater for males than that for females. Awareness of the risk factors for depression may aid in early screening and intervention and improve overall patient outcomes.

Predictors of readmission after craniotomy for meningioma resection: a nationwide readmission database analysis.

BACKGROUND: Meningiomas are the most common benign primary brain tumors. The mainstay of treatment, surgical resection, is often curative. Given the excellent prognosis of these lesions, minimizing perioperative complications is of the utmost importance. With the establishment of the National Readmissions Database (NRD), researchers are now able to identify variables associated with postoperative complications beyond the index admission. OBJECTIVE: In this study, we sought to identify the leading causes for non-elective readmission and variables associated with increased likelihood of readmission at 30 and 90 days after discharge following a craniotomy for meningioma resection. METHODS: Adult inpatients who underwent craniotomy for meningioma resection between 2010 and 2014 were queried from the NRD. All-cause readmissions following craniotomy at 30 and 90 days were identified, and a multivariable logistic regression model was used to characterize independent risk factors. RESULTS: Among 26,034 patients who received craniotomy for meningioma resection, 2825 (10.9%) were readmitted at 30 days and 3436 (16.1%) were readmitted at 90 days. Postoperative wound infection was the most common readmission diagnosis, occurring in 9.32% and 10.2% of 30- and 90-day readmissions respectively. Patient factors associated with increased likelihood of readmission included male gender, greater illness severity, non-routine discharge, index length of hospitalization, and having Medicare or Medicaid insurance. CONCLUSIONS: Readmission following craniotomy for meningioma resection occurs at a clinically significant rate. Several patient factors were identified in association with all-cause 30- and 90-day readmissions. Further studies are required to identify means for preventing complications following discharge in these vulnerable patient populations.

miR-18a Inhibits BMP4 and HIF-1α Normalizing Brain Arteriovenous Malformations.

RATIONALE: Brain arteriovenous malformations (AVMs) are abnormal tangles of vessels where arteries and veins directly connect without intervening capillary nets, increasing the risk of intracerebral hemorrhage and stroke. Current treatments are highly invasive and often not feasible. Thus, effective noninvasive treatments are needed. We previously showed that AVM-brain endothelial cells (BECs) secreted higher VEGF (vascular endothelial growth factor) and lower TSP-1 (thrombospondin-1) levels than control BEC; and that microRNA-18a (miR-18a) normalized AVM-BEC function and phenotype, although its mechanism remained unclear. OBJECTIVE: To elucidate the mechanism of action and potential clinical application of miR-18a as an effective noninvasive treatment to selectively restore the phenotype and functionality of AVM vasculature. METHODS AND RESULTS: The molecular pathways affected by miR-18a in patient-derived BECs and AVM-BECs were determined by Western blot, RT-qPCR (quantitative reverse transcription polymerase chain reaction), ELISA, co-IP, immunostaining, knockdown and overexpression studies, flow cytometry, and luciferase reporter assays. miR-18a was shown to increase TSP-1 and decrease VEGF by reducing PAI-1 (plasminogen activator inhibitor-1/SERPINE1) levels. Furthermore, miR-18a decreased the expression of BMP4 (bone morphogenetic protein 4) and HIF-1α (hypoxia-inducible factor 1α), blocking the BMP4/ALK (activin-like kinase) 2/ALK1/ALK5 and Notch signaling pathways. As determined by Boyden chamber assays, miR-18a also reduced the abnormal AVM-BEC invasiveness, which correlated with a decrease in MMP2 (matrix metalloproteinase 2), MMP9, and ADAM10 (ADAM metallopeptidase domain 10) levels. In vivo pharmacokinetic studies showed that miR-18a reaches the brain following intravenous and intranasal administration. Intranasal co-delivery of miR-18a and NEO100, a good manufacturing practices-quality form of perillyl alcohol, improved the pharmacokinetic profile of miR-18a in the brain without affecting its pharmacological properties. Ultra-high-resolution computed tomography angiography and immunostaining studies in an Mgp-/- AVM mouse model showed that miR-18a decreased abnormal cerebral vasculature and restored the functionality of the bone marrow, lungs, spleen, and liver. CONCLUSIONS: miR-18a may have significant clinical value in preventing, reducing, and potentially reversing AVM.

Intentional Subtotal Resection of Vestibular Schwannoma: A Reexamination.

Background Treatment of vestibular schwannomas (VS) remains controversial. Historical surgical series prioritized gross total resections (GTR); however, near total resections (NTR) and intentional subtotal resections (STR) aiming at improving cranial nerve outcomes are becoming more popular. Objective The main purpose of this article is to assess the tumor control and facial nerve outcomes in VS patients treated with STR or NTR. Methods VS patients undergoing STR or NTR at our institution between 1984 and 2016 were retrospectively reviewed. Patient demographics, extent of tumor resection, facial nerve injury, tumor recurrence, and need for Gamma Knife radiosurgery were analyzed. Facial nerve outcomes were quantified using House-Brackmann (HB) scores. Tumor regrowth was defined by the San Francisco criteria. Results Four-hundred fifty-seven VS resections were performed in a 32-year period. Sixty cases met inclusion criteria. The mean (range) follow-up duration was 30.9 (12-103) months. The STR cohort ( n = 33) demonstrated regrowth in 12 patients (36.3%) at an average of 23.6 months. The NTR cohort ( n = 27) did not experience tumor recurrence. Risk of tumor recurrence was positively correlated with preoperative tumor size ( p = 0.002), size of residual tumor ( p < 0.001), and STR ( p < 0.001). Facial nerve outcomes of HB1-2 were observed in the majority of patients in both cohorts (74.1% NTR, 56% STR), though NTR was associated with a higher likelihood of facial nerve recovery ( p = 0.003). Conclusion GTR remains the gold standard as long as facial nerve outcomes remain acceptable. NTR achieved superior tumor control and higher likelihood of facial nerve recovery compared with STR.