Glioblastoma remodelling of human neural circuits decreases survival.

Gliomas synaptically integrate into neural circuits1,2. Previous research has demonstrated bidirectional interactions between neurons and glioma cells, with neuronal activity driving glioma growth1-4 and gliomas increasing neuronal excitability2,5-8. Here we sought to determine how glioma-induced neuronal changes influence neural circuits underlying cognition and whether these interactions influence patient survival. Using intracranial brain recordings during lexical retrieval language tasks in awake humans together with site-specific tumour tissue biopsies and cell biology experiments, we find that gliomas remodel functional neural circuitry such that task-relevant neural responses activate tumour-infiltrated cortex well beyond the cortical regions that are normally recruited in the healthy brain. Site-directed biopsies from regions within the tumour that exhibit high functional connectivity between the tumour and the rest of the brain are enriched for a glioblastoma subpopulation that exhibits a distinct synaptogenic and neuronotrophic phenotype. Tumour cells from functionally connected regions secrete the synaptogenic factor thrombospondin-1, which contributes to the differential neuron-glioma interactions observed in functionally connected tumour regions compared with tumour regions with less functional connectivity. Pharmacological inhibition of thrombospondin-1 using the FDA-approved drug gabapentin decreases glioblastoma proliferation. The degree of functional connectivity between glioblastoma and the normal brain negatively affects both patient survival and performance in language tasks. These data demonstrate that high-grade gliomas functionally remodel neural circuits in the human brain, which both promotes tumour progression and impairs cognition.

Resting-state functional magnetic resonance imaging with independent component analysis for presurgical seizure onset zone localization: A systematic review and meta-analysis.

OBJECTIVE: One of the greatest challenges of achieving successful surgical outcomes in patients with epilepsy is the ability to properly localize the seizure onset zone (SOZ). Many techniques exist for localizing the SOZ, including intracranial electroencephalography, magnetoencephalography, and stereoelectroencephalography. Recently, resting-state functional magnetic resonance imaging (rs-fMRI) in conjunction with independent component analysis (ICA) has been utilized for presurgical planning of SOZ resection, with varying results. In this meta-analysis, we analyze the current role of rs-fMRI in identifying the SOZ for presurgical planning for patients with drug-resistant epilepsy. Specifically, we seek to demonstrate its current effectiveness compared to other methods of SOZ localization. METHODS: A literature review was conducted using the PubMed, MEDLINE, and Embase databases up to May of 2020. A total of 253 articles were screened, and seven studies were chosen for analysis. Each study was analyzed for SOZ localization by ground truth, SOZ localization by rs-fMRI with ICA, principal component analysis, or intrinsic connectivity contrast, and outcomes of surgery. A meta-analysis was performed to analyze how ground truth compares to rs-fMRI in SOZ localization. RESULTS: The odds ratio comparing ground truth to rs-fMRI was 2.63 (95% confidence interval = 0.66-10.56). Average concordance of rs-fMRI SOZ localization compared with ground truth localization across studies was 71.3%. SIGNIFICANCE: In the hunt for less invasive presurgical planning for epilepsy surgery, rs-fMRI with ICA provides a promising avenue for future standard practice. Our preliminary results show no significant difference in surgical outcomes between traditional standards of SOZ localization and rs-fMRI with ICA. We believe that rs-fMRI could be a step forward in this search. Further investigation comparing rs-fMRI to traditional methods of SOZ localization should be conducted, with the hope of moving toward relying solely on noninvasive screening methods.

Impact of Obesity on Anterior Cervical Discectomy and Fusion (ACDF): Postoperative Morbidity and Mortality.

AIM: To investigate the impact of obesity on postoperative morbidity and mortality in patients who underwent anterior cervical discectomy and fusion (ACDF). MATERIAL AND METHODS: The American College of Surgeons' National Surgical Quality Improvement Project (NSQIP) files from 2006 to 2019 were queried for all patients who underwent an ACDF. Fisher exact tests were used in analyzing univariate differences in preoperative comorbidities and postoperative morbidity and mortality between patients with and without obesity (BMI ?30 kg/ m < sup > 2 < /sup > ). Results with a p value < 0.05 were considered statistically significant. Multivariable logistic regression models were used in determining the independent impact of obesity on ACDF postoperative morbidity and mortality. A p value < 0.017 was required for multivariate statistical significance. RESULTS: There were 96,882 patients who underwent an ACDF from 2006 to 2019 found. 53.77% had non-obese BMI. Patients had statistically significant differences in most perioperative comorbidities and postoperative outcomes on univariate analysis. On multivariate analysis, patients with obesity has decreased adjusted odds of wound infections (aOR=0.7208, CI 0.574-0.9075, p=0.0053), pulmonary events (aOR=0.7939, CI 0.6903-0.9129, p=0.0012), sepsis (aOR=0.5670, CI 0.4359-0.7374, p=2.32E-05), transfusion requirements (aOR=0.5396, CI 0.4498-0.6473, p=3.04E-11), return to operating room (aOR=0.7537, CI 0.6727-0.8447, p=1.17E-06), and length of stay > 10 days (aOR=0.7061, CI 0.6438-0.7744, p=1.49E-13). CONCLUSION: Obesity is a protective factor toward ACDF postoperative complications. Obesity as a marker of patient selection criteria for ACDF procedures should not be used by spine surgeons.

Postoperative Morbidity and Mortality in Lumbar Spine Surgery Patients With Chronic Kidney Disease and Chronic Steroid Use.

BACKGROUND: Perioperative steroids have traditionally been administered during lumbar spine surgery in order to decrease local inflammation and prevent scar tissue formation, which can otherwise contribute to significant, long-lasting postoperative pain due to the formation of epidural fibrosis around lumbar nerve roots. However, the use of steroids in lumbar spine patients has raised concerns of postoperative wound complications caused by corticosteroid-induced immunomodulatory effects and changes in collagen synthesis. Patients with chronic kidney disease (CKD) undergoing spine surgery are at a particularly elevated risk of various complications due to chronic CKD-related systemic inflammation and endothelial dysfunction. It is currently uncertain whether chronic steroid use in CKD patients exerts a protective effect postoperatively due to decreased systemic inflammation or instead is correlated with increased rates of wound complications. RESULTS: Using adjusted odds ratios to control for CKD-related comorbidities, our study of lumbar spine fusion patients who were chronic steroid users vs nonusers found no significant differences in rates of postoperative wound infections in later stage CKD patients. However, we also did not observe statistically significant reductions in hospital length of stay or rates of 30-day mortality, sepsis, or cardiac, pulmonary, and renal events. CONCLUSIONS: Our results indicate chronic steroid use neither contributes significantly to rates of wound infections nor exerts a protective effect against postoperative inflammatory complications in lumbar spine patients with CKD. CLINICAL RELEVANCE: Our findings do not support the practice of holding steroids in chronic users prior to lumbar spine surgery. Perioperative steroids do not appear to increase the risk of postoperative complications, but neither do they improve lumbar spine patient outcomes.

Correlation of natural language assessment results with health-related quality of life in adult glioma patients.

OBJECTIVE: Impairments of speech are common in patients with glioma and negatively impact health-related quality of life (HRQoL). The benchmark for clinical assessments is task-based measures, which are not always feasible to administer and may miss essential components of HRQoL. In this study, the authors tested the hypothesis that variations in natural language (NL) correlate with HRQoL in a pattern distinct from task-based measures of language performance. METHODS: NL use was assessed using audio samples collected unobtrusively from 18 patients with newly diagnosed low- and high-grade glioma. NL measures were calculated using manual segmentation and correlated with Quality of Life in Neurological Disorders (Neuro-QoL) outcomes. Spearman's rank-order correlation was used to determine relationships between Neuro-QoL scores and NL measures. RESULTS: The distribution of NL measures across the entire patient cohort included a mean ± SD total time speaking of 11.5 ± 2.20 seconds, total number of words of 27.2 ± 4.44, number of function words of 10.9 ± 1.68, number of content words of 16.3 ± 2.91, and speech rate of 2.61 ± 0.20 words/second. Speech rate was negatively correlated with functional domains (rho = -0.62 and p = 0.007 for satisfaction with social roles; rho = -0.74 and p < 0.001 for participation in social roles) but positively correlated with impairment domains (rho = 0.58 and p = 0.009 for fatigue) of Neuro-QoL. CONCLUSIONS: Assessment of NL at the time of diagnosis may be a useful measure in the context of treatment planning and monitoring outcomes for adult patients with glioma.

Central Nervous System Plasticity Influences Language and Cognitive Recovery in Adult Glioma.

Gliomas exist within the framework of complex neuronal circuitry in which network dynamics influence both tumor biology and cognition. The generalized impairment of cognition or loss of language function is a common occurrence for glioma patients. The interface between intrinsic brain tumors such as gliomas and functional cognitive networks are poorly understood. The ability to communicate effectively is critically important for receiving oncological therapies and maintaining a high quality of life. Although the propensity of gliomas to infiltrate cortical and subcortical structures and disrupt key anatomic language pathways is well documented, there is new evidence offering insight into the network and cellular mechanisms underpinning glioma-related aphasia and aphasia recovery. In this review, we will outline the current understanding of the mechanisms of cognitive dysfunction and recovery, using aphasia as an illustrative model.

Racial Disparities Affecting Postoperative Outcomes After Brain Tumor Resection.

OBJECTIVE: To investigate racial disparities in 30-day postoperative outcomes of craniotomy for glioma resection. METHODS: 2006-2019 American College of Surgeons' National Surgical Quality Improvement Program files were queried for all patients who underwent a craniotomy for a supratentorial glioma resection. Racial disparities in preoperative variables were studied between the demographic cohorts of Asian, African Americans, Hispanics, and Caucasian. Fisher exact tests were used to examine association of preoperative variables with race. Multivariable logistic regression models, adjusted for all preoperative variables associated with race, were used to determine the odds ratios of postoperative outcomes for each demographic cohort in comparison with Caucasian patients. RESULTS: A total of 12,544 patients were identified: 4% Asian, 5% African American, 7% Hispanic, and 85% Caucasian. African American patients had significantly higher adjusted odds than Caucasian patients of major adverse cardiovascular events (adjusted odds ratio [aOR]: 1.827, 95% confidence interval [CI]: 1.155-2.891, P = 0.01), pulmonary events (aOR: 1.683, 95% CI: 1.145-2.473, P = 0.008), and urinary tract infection (aOR: 2.016, 95% CI: 1.221-3.327, P = 0.006). Asian patients had significantly higher odds than Caucasian patients of requiring a transfusion (aOR: 2.094, 95% CI: 1.343-3.266, P = 0.001). All demographic cohorts had higher odds of having an extended length of stay than Caucasian patients. CONCLUSIONS: African American patients who undergo a craniotomy for glioma resection have almost twice the odds of Caucasian patients of having a postoperative major cardiovascular complication, pulmonary complication, or urinary tract infection. All minority groups have higher odds of an extended length of stay as compared with Caucasian patients.

Coagulation Profile as a Significant Risk Factor for Short-Term Complications and Mortality after Anterior Cervical Discectomy and Fusion.

BACKGROUND: Cervical degenerative disc disease is the most common indication for anterior cervical discectomy and fusion. Given the possible complications, patients are stratified before anterior cervical discectomy and fusion by preoperative risk factors to optimize treatment. One preoperative factor is a patient's coagulation profile. METHODS: The American College of Surgeons-National Surgical Quality Improvement Database was used to identify patient preoperative coagulation profile and postoperative complications. By generating binary logistic regression models, each of the 4 abnormal coagulation categories (bleeding disorder, low platelet count, high partial thromboplastin time, and high international normalized ratio [INR]) were analyzed for their independent impact on increased risk for complications compared with the control cohort. RESULTS: A total of 61,977 patients were assessed. The most common abnormal coagulation was abnormal platelet count (n = 2149). The most common postoperative outcome was an extended length of hospital stay among patients with an abnormal coagulation profile relative to the control cohort. After multivariate analysis, patients with an abnormal INR (odds ratio, 2.2 [1.3-3.8]; P = 0.003) or abnormal platelet count (odds ratio, 1.5 [1.2-2.1]; P = 0.003) had a higher chance of having an extended length of hospital stay relative to patients having a normal coagulation profile. Having an abnormal INR was found to be associated with an increased risk for having "Any complication." CONCLUSIONS: Our results show significant differences in the incidence rates of a multitude of complications among the 5 groups based on univariate analysis. Patients with any abnormal coagulation disorder had increased rates of developing any complication or having an extended length of hospital stay.

Profile of Data Sharing in the Clinical Neurosciences.

IMPORTANCE:  In today's climate of high healthcare costs and limited research resources, much attention has been given to inefficiency in research. Open access to research data has been proposed as a way to pool resources and make the most of research funding while also promoting transparency and scientific rigor.  Objective: The clinical neurosciences stand to benefit greatly from the potential opportunities afforded by open data, and we sought to evaluate the current state of publicly available research findings and data sharing policies within the clinical neurosciences.  Design: The Clarivate Analytics Web of Science journal citation reports for 2017 were used to sort journals in the category 'Clinical Neurosciences' by impact factor. The top 50 journals were selected and reviewed, but data was only collected from journals focused on original research (42/50). For each journal we reviewed the 10 most recent original research articles for 2016, 2017, and 2018 as designated by Scopus.  Results: A data sharing policy existed for 60% (25/42) of the journals reviewed. Of the articles studied 41% (517/1255) contained source data, and the amount of articles with available source data increased from 2016 to 2018. Of all the articles reviewed, 49.4% (620/1255) were open access. Overall, 6.9% (87/1255) of articles had their source data accessible outside of the manuscript (e.g. registries, databases, etc.) and 8.9% (112/1255) addressed the availability of their source data within the publication itself. The availability of source data outside the manuscript and in-article discussion of source data availability both increased from 2016 to 2018. Only 3.9% (49/1255) of articles reviewed reported negative results for their primary outcome, and 7.6% (95/1255) of the articles could not be defined as primarily reporting positive or negative findings (characterization studies, census reporting, etc.). The distribution of negative versus positive results reported showed no significant trend over the years studied.  Conclusion and Relevance: Our results demonstrate an opportunity for increased data sharing in neuroscience original research. These findings also suggest a trend towards increased adoption of open data sharing policies among journals and increased availability of unprocessed data in publications. This can increase the quality and speed at which new research is developed in the clinical neurosciences.