Pathogenesis of Intracranial Aneurysms

Introduction: Intracranial aneurysms (IA) are a common neurological problem, the rupture of which frequently constitutes a catastrophic neurological event. While the pathogenesis is largely unknown, it is believed that both genetic and environmental factors work in concert to some degree within patients. Our goal was to take a comprehensive approach to understanding the pathogenesis of IA by identifying factors leading to the formation, growth and rupture of IA. Methods: Since 1994, we have recruited patients and families with IA into the Yale Brain Aneurysm Database. Information regarding aneurysm characteristics (size, location, number), patient characteristics (age, medical, and social history), and family history were recorded. We analyzed this database for environmental factors associated with aneurysmal rupture. Within the same database, we identified and analyzed kindreds with a high IA incidence and penetrance using genome-wide linkage analysis. Collaborations with other centers provided additional kindreds to analyze and confirm our results. Results: Analysis of our database revealed hypertensive patients with IA ≤ 7mm were 2.6 times more likely to rupture (p = .01, 95% CI: 1.21, 5.53) than normotensive patients. Posterior circulation aneurysms were 3.5 times more likely to rupture than anterior circulation aneurysms (p = .048, 95% CI: 0.95, 19.4). Further, genome-wide linkage analysis revealed significant linkage to a single locus, with a lod score of 4.2 at 1p34-36. Conclusions: We identified hypertension, young age, and posterior circulation as significant risk factors for rupture among patients with small aneurysms (≤ 7mm). Additionally, we are the first to map the gene responsible for IA to chromosome 1p34-26

Conflict of Interest in Spine Research Reporting

Background: Medical studies are more likely to report favorable findings when a conflict of interest is declared. We aim to quantify and determine the effect of author disclosure of conflict of interest on scientific reporting. Methods: Abstracts from an international spine research meeting (North American Spine Society 2010) were selected that specifically evaluated a device, biologic, or proprietary procedure. They were then made anonymous to reviewers. An item of interest was established in each of the abstracts in order to standardize evaluation. Next, three blinded reviewers independently rated the abstracts as favorable, neutral, or unfavorable with regard to the item of interest. Additionally, the blinded reviewers attempted to predict whether a related disclosure was made. The meeting disclosure index was used to tabulate the minimum US dollar value attributable to disclosures. Results: Of the 344 total abstracts, 76 met inclusion criteria. In 79%, a related conflict of interest was reported. The amount of the disclosure was incompletely reported in 30% of cases. Where available, it averaged a cumulative minimum of $219,634 USD per abstract. The results of the abstracts were judged to be favorable, neutral, and unfavorable in 63%, 32% and 5% of abstracts, respectively. There was no correlation between the presence of a related disclosure and the findings of the studies (p = 0.81), although interpretation of this is limited by a small sample size and an overall apparent bias to report favorable studies. Additionally, the blinded reviewers were unable to predict whether a related disclosure was made (p = 0.40). Conclusion: No association existed between the presence of a related disclosure and the results of the studies. While the actual compliance with reporting a potential conflict of interest is unable to be determined, the value amount related to the disclosures made was inadequately reported according to meeting guidelines

Socioeconomic Status Correlates with the Prevalence of Advanced Coronary Artery Disease in the United States

Background: Increasingly studies have identified socioeconomic factors adversely affecting healthcare outcomes for a multitude of diseases. To date, however, there has not been a study correlating socioeconomic details from nationwide databases on the prevalence of advanced coronary artery disease. We seek to identify whether socioeconomic factors contribute to advanced coronary artery disease prevalence in the United States. Methods and Findings: State specific prevalence data was queried form the United States Nationwide Inpatient Sample for 2009. Patients undergoing percutaneous coronary angioplasty and coronary artery bypass graft were identified as principal procedures. Non-cardiac related procedures, lung lobectomy and hip replacement (partial and total) were identified and used as control groups. Information regarding prevalence was then merged with data from the Behavioral Risk Factor Surveillance System, the largest, on-going telephone health survey system tracking health conditions and risk behaviors in the United States. Pearson's correlation coefficient was calculated for individual socioeconomic variables including employment status, level of education, and household income. Household income and education level were inversely correlated with the prevalence of percutaneous coronary angioplasty (−0.717; −0.787) and coronary artery bypass graft surgery (−0.541; −0.618). This phenomenon was not seen in the non-cardiac procedure control groups. In multiple linear regression analysis, socioeconomic factors were significant predictors of coronary artery bypass graft and percutaneous transluminal coronary angioplasty (p<0.001 and p = 0.005, respectively). Conclusions: Socioeconomic status is related to the prevalence of advanced coronary artery disease as measured by the prevalence of percutaneous coronary angioplasty and coronary artery bypass graft surgery

Volumetric analysis of syringomyelia following hindbrain decompression for Chiari malformation Type I: syringomyelia resolution follows exponential kinetics

Object: Resolution of syringomyelia is common following hindbrain decompression for Chiari malformation, yet little is known about the kinetics governing this process. The authors sought to establish the volumetric rate of syringomyelia resolution. Methods: A retrospective cohort of patients undergoing hindbrain decompression for a Chiari malformation Type I with preoperative cervical or thoracic syringomyelia was identified. Patients were included in the study if they had at least 3 neuroimaging studies that detailed the entirety of their preoperative syringomyelia over a minimum of 6 months postoperatively. The authors reconstructed the MR images in 3 dimensions and calculated the volume of the syringomyelia. They plotted the syringomyelia volume over time and constructed regression models using the method of least squares. The Akaike information criterion and Bayesian information criterion were used to calculate the relative goodness of fit. The coefficients of determination R2 (unadjusted and adjusted) were calculated to describe the proportion of variability in each individual data set accounted for by the statistical model. Results: Two patients were identified as meeting inclusion criteria. Plots of the least-squares best fit were identified as 4.01459e−0.0180804x and 13.2556e−0.00615859x. Decay of the syringomyelia followed an exponential model in both patients (R2 = 0.989582 and 0.948864). Conclusions: Three-dimensional analysis of syringomyelia resolution over time enables the kinetics to be estimated. This technique is yet to be validated in a large cohort. Because syringomyelia is the final common pathway for a number of different pathological processes, it is possible that this exponential only applies to syringomyelia related to treatment of Chiari malformation Type I

Postoperative Intensive Care Unit Requirements After Elective Craniotomy

Objective: Commonly, patients undergoing craniotomy are admitted to an intensive care setting post-operatively to allow for close monitoring. We aim to determine the frequency with which patients who have undergone elective craniotomies require intensive care unit level interventions or experience significant complications during the post-operative period to identify a subset of patients for whom an alternative to ICU level care may be appropriate. Methods: Following Institutional Review Board approval, a prospective, consecutive cohort of adult patients undergoing elective craniotomy was established at the Massachusetts General Hospital between the dates of April 2010 and March 2011. Inclusion criteria were intradural operations requiring craniotomy performed on adults (18 years of age or greater). Exclusion criteria were cases of an urgent or emergent nature, patients who remained intubated post-operatively, and patients who had a ventriculostomy drain in place at the conclusion of the case. Results: 400 patients were analyzed. Univariate analysis revealed that diabetics (p = 0.00047), patients who required intra-operative blood product administration (p = 0.032), older patients (p < 0.0001), patients with higher intra-operative blood losses (p = 0.041), and patients who underwent longer surgical procedures (p = 0.021) were more likely to require ICU-level interventions or experience significant post-operative complications. Multivariate analysis only found diabetes (p = 0.0005) and age (p = 0.0091) to be predictive of a patient’s need for post-operative intensive care unit admission. Conclusions: Diabetes and older age predict the need for ICU-level intervention after elective craniotomy. Properly selected patients may not require post-craniotomy ICU monitoring. Further study of resource utilization is necessary to validate these preliminary findings, particularly in different hospital types

Retrievable stent thrombectomy in the treatment of acute ischemic stroke: Analysis of a revolutionizing treatment technique

Acute ischemic stroke resulting from intracranial vessel occlusion is associated with high morbidity and mortality. The mainstays of therapy are fibrinolytics and mechanical thrombectomy in properly selected patients. A new Food and Drug Administration-approved technology to perform thrombectomy, retrievable stenting, may provide superior revascularization rates and improved patient outcomes. We analyzed the cumulative human experience reported for the Trevo Pro Retrieval System (Stryker, Kalamazoo, MI, USA) and the Solitaire FR Revascularization Device (ev3, Irvine, CA, USA) as the definitive treatment for acute ischemic stroke. A literature search was undertaken to identify studies using the retrievable stents published up to September 2012. Nineteen studies identified a total of 576 patients treated with either the Trevo (n = 221) or Solitaire (n = 355) devices. Pooled data analysis identified baseline National Institutes of Health Stroke Scale scores of 18.5 ± 0.289 (standard error of the mean) and 17.9 ± 0.610, and time to recanalization of 53.9 ± 23.6 minutes and 59.0 ± 8.0 minutes for the Trevo and Solitaire groups, respectively. Recanalization was variably defined by individual studies, most commonly achieving at least a thrombolysis in cerebral infarction score of 2a–3 or a thrombolysis in myocardial infarction score of 2–3. Revascularization (83%, 82%), mortality (31%, 14%), hemorrhage (8%, 6%), device complications (5%, 6%), and good patient outcomes (51%, 47%) were found with the Trevo and Solitaire devices, respectively. Preliminary analysis reveals excellent clinical outcomes for retrievable stent technology. This may be attributable to both high rates of revascularization with a relatively short time to perfusion restoration

Clinical features of brain metastasis from salivary gland tumors

Salivary gland tumors comprise a group of 24 tumor subtypes with a wide range of clinical behaviors and propensities for metastasis. Several prognostic factors have been identified that help predict the development of systemic metastases, most commonly to the lung, liver, or bone. Metastases to the brain are rare. To better understand the behavior of salivary gland tumors that metastasise to the brain, we performed a retrospective cohort analysis on a series of patients to highlight features of their medical and surgical management. From 2007 to 2011, a database of 4117 elective craniotomies were queried at a single institution to identify patients surgically treated for salivary gland metastases to the brain. Three patients were identified. Histologic subtypes included salivary duct carcinoma, poorly differentiated carcinoma, and papillary mucinous adenocarcinoma. They had all undergone previous treatment for their primary malignancy. The mean time to intracranial metastasis was 48 months from initial diagnosis (range, 14–91 months). Treatment for intracranial metastases included surgical resection, whole brain radiation, stereotactic radiosurgery, and chemotherapy. Intracranial metastases from salivary gland tumors are rare, present years after diagnosis of the primary tumor, and are treatable with multimodality therapy

Time interval to surgery and outcomes following the surgical treatment of acute traumatic subdural hematoma

Although the pre-surgical management of patients with acute traumatic subdural hematoma prioritizes rapid transport to the operating room, there is conflicting evidence regarding the importance of time interval from injury to surgery with regards to outcomes. We sought to determine the association of surgical timing with outcomes for subdural hematoma. A retrospective review was performed of 522 consecutive patients admitted to a single center from 2006–2012 who underwent emergent craniectomy for acute subdural hematoma. After excluding patients with unknown time of injury, penetrating trauma, concurrent cerebrovascular injury, epidural hematoma, or intraparenchymal hemorrhage greater than 30 mL, there remained 45 patients identified for analysis. Using a multiple regression model, we examined the effect of surgical timing, in addition to other variables on in-hospital mortality (primary outcome), as well as the need for tracheostomy or gastrostomy (secondary outcome). We found that increasing injury severity score (odds ratio [OR] 1.146; 95% confidence interval [CI] 1.035–1.270; p = 0.009) and age (OR1.066; 95%CI 1.006–1.129; p = 0.031) were associated with in-hospital mortality in multivariate analysis. In this model, increasing time to surgery was not associated with mortality, and in fact had a significant effect in decreasing mortality (OR 0.984; 95%CI 0.971–0.997; p = 0.018). Premorbid aspirin use was associated with a paradoxical decrease in mortality (OR 0.019; 95%CI 0.001–0.392; p = 0.010). In this patient sample, shorter time interval from injury to surgery was not associated with better outcomes. While there are potential confounding factors, these findings support the evaluation of rigorous preoperative resuscitation as a priority in future study

Safe surgery for glioblastoma: Recent advances and modern challenges.

One of the major challenges during glioblastoma surgery is balancing between maximizing extent of resection and preventing neurological deficits. Several surgical techniques and adjuncts have been developed to help identify eloquent areas both preoperatively (fMRI, nTMS, MEG, DTI) and intraoperatively (imaging (ultrasound, iMRI), electrostimulation (mapping), cerebral perfusion measurements (fUS)), and visualization (5-ALA, fluoresceine)). In this review, we give an update of the state-of-the-art management of both primary and recurrent glioblastomas. We will review the latest surgical advances, challenges, and approaches that define the onco-neurosurgical practice in a contemporary setting and give an overview of the current prospective scientific efforts

The PROGRAM study: awake mapping versus asleep mapping versus no mapping for high-grade glioma resections: study protocol for an international multicenter prospective three-arm cohort study.

INTRODUCTION The main surgical dilemma during glioma resections is the surgeon's inability to accurately identify eloquent areas when the patient is under general anaesthesia without mapping techniques. Intraoperative stimulation mapping (ISM) techniques can be used to maximise extent of resection in eloquent areas yet simultaneously minimise the risk of postoperative neurological deficits. ISM has been widely implemented for low-grade glioma resections backed with ample scientific evidence, but this is not yet the case for high-grade glioma (HGG) resections. Therefore, ISM could thus be of important value in HGG surgery to improve both surgical and clinical outcomes. METHODS AND ANALYSIS This study is an international, multicenter, prospective three-arm cohort study of observational nature. Consecutive HGG patients will be operated with awake mapping, asleep mapping or no mapping with a 1:1:1 ratio. Primary endpoints are: (1) proportion of patients with National Institute of Health Stroke Scale deterioration at 6 weeks, 3 months and 6 months after surgery and (2) residual tumour volume of the contrast-enhancing and non-contrast-enhancing part as assessed by a neuroradiologist on postoperative contrast MRI scans. Secondary endpoints are: (1) overall survival and (2) progression-free survival at 12 months after surgery; (3) oncofunctional outcome and (4) frequency and severity of serious adverse events in each arm. Total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year. ETHICS AND DISSEMINATION The study has been approved by the Medical Ethics Committee (METC Zuid-West Holland/Erasmus Medical Center; MEC-2020-0812). The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media. TRIAL REGISTRATION NUMBER ClinicalTrials.gov ID number NCT04708171 (PROGRAM-study), NCT03861299 (SAFE-trial)