Sequential deactivation across the thalamus-hippocampus-mPFC pathway during loss of consciousness.

How consciousness is lost in states such as sleep or anesthesia remains a mystery. To gain insight into this phenomenon, we conducted concurrent recordings of electrophysiology signals in the anterior cingulate cortex and whole-brain functional magnetic resonance imaging (fMRI) in rats exposed to graded propofol, undergoing the transition from consciousness to unconsciousness. Our results reveal that upon the loss of consciousness (LOC), as indicated by the loss of righting reflex, there is a sharp increase in low-frequency power of the electrophysiological signal. Additionally, simultaneously measured fMRI signals exhibit a cascade of deactivation across a pathway including the hippocampus, thalamus, and medial prefrontal cortex (mPFC) surrounding the moment of LOC, followed by a broader increase in brain activity across the cortex during sustained unconsciousness. Furthermore, sliding window analysis demonstrates a temporary increase in synchrony of fMRI signals across the hippocampus-thalamus-mPFC pathway preceding LOC. These data suggest that LOC might be triggered by sequential activities in the hippocampus, thalamus and mPFC, while wide-spread activity increases in other cortical regions commonly observed during anesthesia-induced unconsciousness might be a consequence, rather than a cause of LOC. Taken together, our study identifies a cascade of neural events unfolding as the brain transitions into unconsciousness, offering critical insight into the systems-level neural mechanisms underpinning LOC.

Exploring memory-related network via dorsal hippocampus suppression.

Memory is a complex brain process that requires coordinated activities in a large-scale brain network. However, the relationship between coordinated brain network activities and memory-related behavior is not well understood. In this study, we investigated this issue by suppressing the activity in the dorsal hippocampus (dHP) using chemogenetics and measuring the corresponding changes in brain-wide resting-state functional connectivity (RSFC) and memory behavior in awake rats. We identified an extended brain network contributing to the performance in a spatial-memory related task. Our results were cross-validated using two different chemogenetic actuators, clozapine (CLZ) and clozapine-N-oxide (CNO). This study provides a brain network interpretation of memory performance, indicating that memory is associated with coordinated brain-wide neural activities. Significance Statement: Successful memory processes require coordinated activity in a large-scale brain network, extending beyond a few key, well-known brain regions like the hippocampus. However, the specific brain regions involved and how they orchestrate their activity that is pertinent to memory processing remain unclear. Our study, using a chemogenetics-rsfMRI- behavior approach in awake rats, elucidates a comprehensive framework of the extended memory-associated network. This knowledge offers a broader interpretation of memory processes, enhancing our understanding of the neural mechanisms behind memory function, particularly from a network perspective.

Optimal Frequency in Repetitive Transcranial Magnetic Stimulation for the Management of Chronic Pain: A Network Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Repetitive Transcranial Magnetic Stimulation (rTMS) has been shown to be effective for pain modulation in a variety of pathological conditions causing neuropathic pain. The purpose of this study is to conduct a network meta-analysis (NMA) of randomized control trials to identify the most optimal frequency required to achieve chronic pain modulation using rTMS. METHODS: A comprehensive search was conducted in electronic databases to identify randomized controlled trials investigating the efficacy of rTMS for chronic pain management. A total of 24 studies met the inclusion criteria, and a NMA was conducted to identify the most effective rTMS frequency for chronic pain management. RESULTS: Our analysis revealed that high frequency rTMS (20 Hz) was the most effective frequency for chronic pain modulation. Patients treated with 20 Hz had lower pain levels than those treated at 5 Hz (mean difference [MD] = -3.11 [95% confidence interval {CI}: -5.61 - -0.61], P = 0.032) and control (MD = -1.99 [95% CI: -3.11 - -0.88], P = 0.023). Similarly, treatment with 10 Hz had lower pain levels compared to 5 Hz (MD = -2.56 [95% CI: -5.05 - -0.07], P = 0.045) and control (MD = -1.44 [95% CI: -2.52 - -0.36], P = 0.031). 20 Hz and 10 Hz were not statistically different. CONCLUSIONS: This NMA suggests that high frequency rTMS (20 Hz) is the most optimal frequency for chronic pain modulation. These findings have important clinical implications and can guide healthcare professionals in selecting the most effective frequency for rTMS treatment in patients with chronic pain.

Disparity in temporal and spatial relationships between resting-state electrophysiological and fMRI signals.

Resting-state brain networks (RSNs) have been widely applied in health and disease, but their interpretation in terms of the underlying neural activity is unclear. To systematically investigate this cornerstone issue, here we simultaneously recorded whole-brain resting-state functional magnetic resonance imaging (rsfMRI) and electrophysiology signals in two separate brain regions in rats. Our data show that for both recording sites, band-specific local field potential (LFP) power-derived spatial maps can explain up to 90% of the spatial variance of RSNs obtained by the rsfMRI signal. Paradoxically, the time series of LFP band power can only explain up to 35% of the temporal variance of the local rsfMRI time course from the same site. In addition, regressing out time series of LFP power from rsfMRI signals has limited impact on the spatial patterns of rsfMRI-based RSNs. This disparity in the spatial and temporal relationships between resting-state electrophysiology and rsfMRI signals suggest that the electrophysiological activity alone does not account for all effects in the rsfMRI signal. To further interpret this disparity, we propose a model hypothesizing that a significant component in the rsfMRI signal is driven by electrophysiology-invisible neural activities that are active in neurovascular coupling. Temporally, this electrophysiology-invisible signal is weakly correlated to electrophysiology data. However, as signaling of these two types of neural activities are both constrained by the same anatomical backbone, they can generate similar RSN spatial patterns. These data and the model provide a new perspective of our interpretation of RSNs.

Influence of Body Mass Index on Surgical and Patient Outcomes for Cervical Spine Surgery.

STUDY DESIGN: Secondary analysis of prospectively collected registry. OBJECTIVE: We aim to investigate the effects of body mass index (BMI) on postsurgical cervical spine surgery outcomes and identify a potential substratification of obesity with worse outcomes. SUMMARY OF BACKGROUND DATA: The impact of BMI on cervical spine surgery is unknown, with controversial outcomes for patients high and low BMI. METHODS: The cervical spine Quality Outcomes Database was queried for a total of 10,381 patients who underwent single-stage cervical spine surgery. Patients were substratified into 6 groups based on BMI. Surgical outcomes, complications, hospitalization outcomes, and patient-reported outcomes for each cohort, including modified Japanese Orthopedic Association Score, Numeric Rating Scale arm pain, Numeric Rating Scale neck pain, Neck Disability Index, and EuroQol Health Survey, were assessed. Univariate analysis was performed for 3- and 12-month follow-up after surgical intervention. RESULTS: Obese patients (class I, II, and III) requiring spine surgery were statistically younger than nonobese patients and had higher rates of diabetes compared with normal BMI patients. The surgical length was found to be longer for overweight and all classes of obese patients ( P < 0.01). Class III obese patients had higher odds of postoperative complications. Patients with class II and III obesity had lower odds of achieving optimal modified Japanese Orthopedic Association Score at 3 months [OR = 0.8 (0.67-0.94), P < 0.01, OR = 0.68 (0.56-0.82), P < 0.001, respectively] and 12 months [OR = 0.82 (0.68-0.98), P = 0.03, OR = 0.79 (0.64-0.98), P = 0.03, respectively]. CONCLUSIONS: This study investigates the relationship between substratified BMI and postoperative outcomes of cervical spine surgery. Class II and III obese patients have substantially greater risk factors and poor outcomes postoperatively. In addition, low BMI also presents unique challenges for patients. Further research is needed for comprehensive analysis on outcomes of cervical spine surgery after correcting BMI.

Diagnostic predictive values for sport-related concussions: a systematic review and diagnostic meta-analysis.

OBJECTIVE: Sport-related concussions (SRCs) can cause significant neurological symptoms, and approximately 10%-15% of athletes with SRC experience a prolonged recovery. Given the lack of visible injury on brain imaging and their varied presentations, concussions can be difficult to diagnose. A variety of tests and examination methods have been used to elicit a concussion diagnosis; however, the sensitivity and specificity of these tests are variable. The authors performed a systematic review and meta-analysis to evaluate the sensitivity and specificity of standardized tests and visible signs like balance and vision changes in the diagnosis of SRC. METHODS: A PRISMA-adherent systematic review of concussion diagnostic examinations was performed using the PubMed, MEDLINE, Scopus, Cochrane, Web of Science, and Google Scholar databases on December 1, 2022. Search terms included "concussion," "traumatic brain injury," "diagnosis," "sensitivity," and "specificity." Each method of examination was categorized into larger group-based symptomatologic presentations or standardized tools. The primary outcome was the diagnosis of concussion. Pooled specificity and sensitivity for each method were calculated using a meta-analysis of proportion and were hierarchically ranked using P-scores calculated from a diagnostic frequentist network meta-analysis. RESULTS: Thirty full-length articles were identified for inclusion, 13 of which evaluated grouped symptomology examinations (balance and overall clinical presentation) and 17 of which evaluated established formalized tools (ImPACT, King-Devick [K-D] Test, Sport Concussion Assessment Tool [SCAT]). The pooled specificity of the examination methods differed minimally (0.8-0.85), whereas the sensitivity varied to a larger degree (0.5-0.88). In a random effects model, the SCAT had the greatest diagnostic yield (diagnostic OR 31.65, 95% CI 11.06-90.57). Additionally, P-score hierarchical ranking revealed SCAT as having the greatest diagnostic utility (p = 0.9733), followed sequentially by ImPACT, clinical presentation, K-D, and balance. CONCLUSIONS: In deciphering which concussion symptom-focused examinations and standardized tools are most accurate in making a concussion diagnosis, the authors found that the SCAT examination has the greatest diagnostic yield, followed by ImPACT, clinical presentation, and K-D, which have comparable value for diagnosis. Given the indirect nature of this analysis, however, further comparative studies are needed to validate the findings.

Social Determinants of Health Impact Spinal Cord Injury Outcomes in Low- and Middle-Income Countries: A Meta-Epidemiological Study.

BACKGROUND AND OBJECTIVES: Traumatic spinal cord injuries (SCI), which disproportionally occur in low- and middle-income countries (LMICs), pose a significant global health challenge. Despite the prevalence and severity of SCI in these settings, access to appropriate surgical care and barriers to treatment remain poorly understood on a global scale, with data from LMICs being particularly scarce and underreported. This study sought to examine the impact of social determinants of health (SDoH) on the pooled in-hospital and follow-up mortality, and neurological outcomes, after SCI in LMICs. METHODS: A systematic review was conducted in adherence to the Preferred Reporting in Systematic Review and Meta-Analysis-guidelines. Multivariable analysis was performed by multivariable linear regression, investigating the impact of the parameters of interest (patient demographics, country SDoH characteristics) on major patient outcomes (in-hospital/follow-up mortality, neurological dysfunction). RESULTS: Forty-five (N = 45) studies were included for analysis, representing 13 individual countries and 18 134 total patients. The aggregate pooled in-hospital mortality rate was 6.46% and 17.29% at follow-up. The in-hospital severe neurological dysfunction rate was 97.64% and 57.36% at follow-up. Patients with rural injury had a nearly 4 times greater rate of severe in-hospital neurological deficits than patients in urban areas. The Gini index, reflective of income inequality, was associated with a 23.8% increase in in-hospital mortality, a 20.1% decrease in neurological dysfunction at follow-up, and a 12.9% increase in mortality at follow-up. CONCLUSION: This study demonstrates the prevalence of injury and impact of SDoH on major patient outcomes after SCI in LMICs. Future initiatives may use these findings to design global solutions for more equitable care of patients with SCI.

Neuroimaging of opioid exposure: a review of preclinical animal models to inform addiction research.

Opioid use results in thousands of overdose deaths each year. To address this crisis, we need a better understanding of the neurobiological mechanisms that drive opioid abuse. The noninvasive imaging tools positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and manganese-enhanced magnetic resonance imaging (MEMRI) can be used to identify how brain activity responds to acute opioid exposure and adapts to chronic drug treatment. These techniques can be performed in humans and animal models, and brain networks identified in animals closely map to the human brain. Animal models have the advantage of being able to systematically examine the independent effects of opioid exposure in a controlled environment accounting for the complex factors that drive opioid misuse in humans. This review synthesizes literature that utilized noninvasive neuroimaging tools (PET, fMRI, and MEMRI) measuring brain activity correlates in animals to understand the neurobiological consequences of exposure to abused opioids. A PubMed search in September 2023 identified 25 publications. These manuscripts were divided into 4 categories based on the route and duration of drug exposure (acute/chronic, active/passive administration). Within each category, the results were generally consistent across drug and imaging protocols. These papers cover a 20-year range and highlight the advancements in neuroimaging methodology during that time. These advances have enabled researchers to achieve greater resolution of brain regions altered by opioid exposure and to identify patterns of brain activation across regions (i.e., functional connectivity) and within subregions of structures. After describing the existing literature, we suggest areas where additional research is needed.

A consensus protocol for functional connectivity analysis in the rat brain.

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. Here we introduce StandardRat, a consensus rat functional magnetic resonance imaging acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired from rats across 46 centers. We developed a reproducible pipeline for analyzing rat data acquired with diverse protocols and determined experimental and processing parameters associated with the robust detection of functional connectivity across centers. We show that the standardized protocol enhances biologically plausible functional connectivity patterns relative to previous acquisitions. The protocol and processing pipeline described here is openly shared with the neuroimaging community to promote interoperability and cooperation toward tackling the most important challenges in neuroscience.

Clinical Benefit of Vagus Nerve Stimulation for Epilepsy: Assessment of Randomized Controlled Trials and Prospective Non-Randomized Studies.

We examined the efficacy of vagal nerve stimulation (VNS) for patients suffering from medically intractable epilepsy. Four randomized controlled trials (RCTs - 3 adult RCTs and 1 pediatric RCT) were identified in our comprehensive literature search. Across the 4 studies, high frequency VNS stimulation (frequency >20 Hz) consistently achieved a greater seizure frequency reduction (23.4-33.1%) relative to low frequency VNS stimulation (1 Hz, .6-15.2%). We identified 2 RCTs examining whether the parameters of stimulation influenced seizure control. These studies reported that VNS achieved seizure control comparable to those reported by the first 4 RCTs (22-43% seizure frequency reduction), irrespective of the parameters utilized for VNS stimulation. In terms of VNS associated morbidity, these morbidities were consistently higher in adults who underwent high frequency VNS stimulation (eg dysphonia 37-66%, dyspnea 6-25.3%). However, no such differences were observed in the pediatric population. Moreover, <2% of patients withdrew from the RCTs/prospective studies due to intolerable symptoms. To provide an assessment of how the risks and benefits of VNS impact the patient experience, 1 study assessed the well-being of enrolled patients (as a secondary end point) and found VNS was associated with an overall improvement in well-being. Consistent with this observation, we identified a prospective, non-randomized study that demonstrated improved quality of life for epilepsy patients managed with VNS and best medical practice relative to best medical practice alone. In aggregate, these RCT studies support the efficacy and benefit of VNS as a neuro-modulatory platform in the management of a subset of medically refractory epilepsy patients.

High-frequency neuronal signal better explains multi-phase BOLD response.

Visual stimulation-evoked blood-oxygen-level dependent (BOLD) responses can exhibit more complex temporal dynamics than a simple monophasic response. For instance, BOLD responses sometimes include a phase of positive response followed by a phase of post-stimulus undershoot. Whether the BOLD response during these phases reflects the underlying neuronal signal fluctuations or is contributed by non-neuronal physiological factors remains elusive. When presenting blocks of sustained (i.e. DC) light ON-OFF stimulations to unanesthetized rats, we observed that the response following a decrease in illumination (i.e. OFF stimulation-evoked BOLD response) in the visual cortices displayed reproducible multiple phases, including an initial positive BOLD response, followed by an undershoot and then an overshoot before the next ON trial. This multi-phase BOLD response did not result from the entrainment of the periodic stimulation structure. When we measured the neural correlates of these responses, we found that the high-frequency band from the LFP power (300 - 3000 Hz, multi-unit activity (MUA)), but not the power in the gamma band (30 - 100 Hz) exhibited the same multiphasic dynamics as the BOLD signal. This study suggests that the post-stimulus phases of the BOLD response can be better explained by the high-frequency neuronal signal.

Wide-field calcium imaging reveals widespread changes in cortical functional connectivity following mild traumatic brain injury in the mouse.

>2.5 million individuals in the United States suffer mild traumatic brain injuries (mTBI) annually. Mild TBI is characterized by a brief period of altered consciousness, without objective findings of anatomic injury on clinical imaging or physical deficit on examination. Nevertheless, a subset of mTBI patients experience persistent subjective symptoms and repeated mTBI can lead to quantifiable neurological deficits, suggesting that each mTBI alters neurophysiology in a deleterious manner not detected using current clinical methods. To better understand these effects, we performed mesoscopic Ca2+ imaging in mice to evaluate how mTBI alters patterns of neuronal interactions across the dorsal cerebral cortex. Spatial Independent Component Analysis (sICA) and Localized semi-Nonnegative Matrix Factorization (LocaNMF) were used to quantify changes in cerebral functional connectivity (FC). Repetitive, mild, controlled cortical impacts induce temporary neuroinflammatory responses, characterized by increased density of microglia exhibiting de-ramified morphology. These temporary neuro-inflammatory changes were not associated with compromised cognitive performance in the Barnes maze or motor function as assessed by rotarod. However, long-term alterations in functional connectivity (FC) were observed. Widespread, bilateral changes in FC occurred immediately following impact and persisted for up to 7 weeks, the duration of the experiment. Network alterations include decreases in global efficiency, clustering coefficient, and nodal strength, thereby disrupting functional interactions and information flow throughout the dorsal cerebral cortex. A subnetwork analysis shows the largest disruptions in FC were concentrated near the impact site. Therefore, mTBI induces a transient neuroinflammation, without alterations in cognitive or motor behavior, and a reorganized cortical network evidenced by the widespread, chronic alterations in cortical FC.

Rates of operative intervention for infection after synthetic or autologous cranioplasty: a National Readmissions Database analysis.

OBJECTIVE: The aim of this study was to characterize the clinical utilization and associated charges of autologous bone flap (ABF) versus synthetic flap (SF) cranioplasty and to characterize the postoperative infection risk of SF versus ABF using the National Readmissions Database (NRD). METHODS: The authors used the publicly available NRD to identify index hospitalizations from October 2015 to December 2018 involving elective ABF or SF cranioplasty after traumatic brain injury (TBI) or stroke. Subsequent readmissions were further characterized if patients underwent neurosurgical intervention for treatment of infection or suspected infection. Survey Cox proportional hazards models were used to assess risk of readmission. RESULTS: An estimated 2295 SF and 2072 ABF cranioplasties were performed from October 2015 to December 2018 in the United States. While the total number of cranioplasty operations decreased during the study period, the proportion of cranioplasties utilizing SF increased (p < 0.001), particularly in male patients (p = 0.011) and those with TBI (vs stroke, p = 0.012). The median total hospital charge for SF cranioplasty was $31,200 more costly than ABF cranioplasty (p < 0.001). Of all first-time readmissions, 20% involved surgical treatment for infectious reasons. Overall, 122 SF patients (5.3%) underwent surgical treatment of infection compared with 70 ABF patients (3.4%) on readmission. After accounting for confounders using a multivariable Cox model, female patients (vs male, p = 0.003), those discharged nonroutinely (vs discharge to home or self-care, p < 0.001), and patients who underwent SF cranioplasty (vs ABF, p = 0.011) were more likely to be readmitted for reoperation. Patients undergoing cranioplasty during more recent years (e.g., 2018 vs 2015) were less likely to be readmitted for reoperation because of infection (p = 0.024). CONCLUSIONS: SFs are increasingly replacing ABFs as the material of choice for cranioplasty, despite their association with increased hospital charges. Female sex, nonroutine discharge, and SF cranioplasty are associated with increased risk for reoperation after cranioplasty.

Resection of disseminated recurrent myxopapillary ependymoma with more than 4-year follow-up: operative nuance for prolonged prone position. Illustrative case.

BACKGROUND: Symptomatic disseminated myxopapillary ependymoma (MPE) in a young person presents a daunting challenge because the risks of prolonged prone positioning and spinal cord injury may outweigh the likelihood of attaining the benefit of gross total resection. OBSERVATIONS: The authors reported the case of a 15-year-old girl with five discrete recurrent spinal cord ependymomas. The patient received a 25-hour surgical procedure for gross total resection of the tumors and fusion over an approximately 33-hour period. She experienced complete resolution of all preoperative neurological symptoms and subsequently received adjuvant radiation therapy. At 52 months after surgery, she was still experiencing neurologically intact, progression-free survival. This case illustrated one of the most extensive recurrent tumor resections for MPE with prolonged disease-free survival reported to date. It may also represent the longest prone position spinal case reported and was notable for a lack of any of the complications commonly associated with the prolonged prone position. LESSONS: The authors discussed the complexity of surgical decision-making in a symptomatic patient with multiple disseminated metastases, technical considerations for resection of intradural and intramedullary spinal cord tumors, and considerations for avoiding complications during prolonged positioning necessary for spinal surgery.

Deriving causal relationships in resting-state functional connectivity using SSFO-based optogenetic fMRI.

Objective.The brain network has been extensively studied as a collection of brain regions that are functionally inter-connected. However, the study of the causal relationship in brain-wide functional connectivity, which is critical to the brain function, remains challenging. We aim to examine the feasibility of using (SSFO)-based optogenetic functional magnetic resonance imaging to infer the causal relationship (i.e. directional information) in the brain network.Approach.We combined SSFO-based optogenetics with fMRI in a resting-state rodent model to study how a local increase of excitability affects brain-wide neural activity and resting-state functional connectivity (RSFC). We incorporated Pearson's correlation and partial correlation analyses in a graphic model to derive the directional information in connections exhibiting RSFC modulations.Main results. When the dentate gyrus (DG) was sensitized by SSFO activation, we found significantly changed activity and connectivity in several brain regions associated with the DG, particularly in the medial prefrontal cortex Our causal inference result shows an 84%-100% accuracy rate compared to the directional information based on anatomical tracing data.Significance.This study establishes a system to investigate the relationship between local region activity and RSFC modulation, and provides a way to analyze the underlying causal relationship between brain regions.

Readmission risk of malignant brain tumor patients undergoing laser interstitial thermal therapy (LITT) and stereotactic needle biopsy (SNB): a covariate balancing weights analysis of the National Readmissions Database (NRD).

PURPOSE: Despite procedural similarities between laser interstitial thermal therapy (LITT) and stereotactic needle biopsy (SNB), LITT induces delayed, pro-inflammatory responses not associated with SNB that may increase the risk of readmission within 30- or 90- days. Here, we explore this hypothesis. METHODS: We queried the National Readmissions Database (NRD, 2010-18) for malignant brain tumor patients who underwent elective LITT or SNB using International Classification of Diseases codes. Readmissions were defined as non-elective inpatient hospitalizations. Survey regression methods and a weighted analysis were utilized to adjust for demographic and clinical differences between LITT and SNB cohorts. RESULTS: During the study period, an estimated 685 malignant brain patients underwent elective LITT and 15,177 underwent elective SNB. Patients undergoing LITT and SNB exhibited comparable median lengths of hospital stay [IQR; LITT = 2 (1, 3); SNB = 1 (1, 2); p = 0.820]. Likelihood of routine discharge was not significantly different between the two procedures (p = 0.263). No significant differences were observed in the odds of 30- or 90-day unplanned readmission between the LITT and SNB cohorts after multivariable adjustment (all p ≥ 0.177). The covariate balancing weighted analysis confirmed comparable 30 or 90-day readmission risk between LITT and SNB treated patients (all p ≥ 0.201). CONCLUSION: The likelihood of 30- and 90-day readmission for malignant brain tumor patients who underwent LITT or SNB are comparable, supporting the safety profile of LITT as therapy for malignant brain cancers.

Mapping spreading depolarisations after traumatic brain injury: a pilot clinical study protocol.

INTRODUCTION: Cortical spreading depolarisation (CSD) is characterised by a near-complete loss of the ionic membrane potential of cortical neurons and glia propagating across the cerebral cortex, which generates a transient suppression of spontaneous neuronal activity. CSDs have become a recognised phenomenon that imparts ongoing secondary insults after brain injury. Studies delineating CSD generation and propagation in humans after traumatic brain injury (TBI) are lacking. Therefore, this study aims to determine the feasibility of using a multistrip electrode array to identify CSDs and characterise their propagation in space and time after TBI. METHODS AND ANALYSIS: This pilot, prospective observational study will enrol patients with TBI requiring therapeutic craniotomy or craniectomy. Subdural electrodes will be placed for continuous electrocorticography monitoring for seizures and CSDs as a research procedure, with surrogate informed consent obtained preoperatively. The propagation of CSDs relative to structural brain pathology will be mapped using reconstructed CT and electrophysiological cross-correlations. The novel use of multiple subdural strip electrodes in conjunction with brain morphometric segmentation is hypothesised to provide sufficient spatial information to characterise CSD propagation across the cerebral cortex and identify cortical foci giving rise to CSDs. ETHICS AND DISSEMINATION: Ethical approval for the study was obtained from the Hennepin Healthcare Research Institute's ethics committee, HSR 17-4400, 25 October 2017 to present. Study findings will be submitted for publication in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT03321370.

Endovascular and Medical Management of Cerebral Venous Thrombosis: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: Management of cerebral venous thrombosis (CVT) involves minimizing expansion of the thrombus and promoting the recanalization of the venous sinus. While current guidelines include indications of endovascular management and anticoagulation with heparin and warfarin, the use of direct-acting oral anticoagulants (DOACs) has increased. In this study, we aim to conduct a network meta-analysis comparing these 3 therapeutic options: standard anticoagulation, DOACs, and endovascular treatments (EVTs). METHODS: Seventeen of 2265 studies identified from 4 publication databases met inclusion criteria for this network meta-analysis. Outcomes analyzed included modified Rankin Scale score, complications, mortality, and 6-month recanalization rates using a frequentist network meta-analysis approach. For each outcome, the preferential order of each intervention was ranked hierarchically based on P-score calculations used for frequentist network meta-analyses. RESULTS: Modified Rankin Scale outcomes were not significantly different based on the type of treatment modality (i.e., standard anticoagulation, DOACs, or EVT). Evaluation of complications demonstrated that patients treated with EVT were significantly more likely to experience a worse outcome than individuals treated with standard anticoagulation (odds ratio [OR] = 1.83, P = 0.04). Other comparisons did not demonstrate a significant difference in adverse events. For all-cause mortality outcomes, EVT demonstrated significantly greater odds of mortality than standard anticoagulation (OR = 1.89, P = 0.02). Mortality between DOACs and standard anticoagulation was not significantly different. When comparing 6-month recanalization rates, DOACs and EVT were significantly more effective than standard anticoagulation (OR = 1.93, OR = 2.2, P < 0.05). EVT followed by DOACs was preferred over standard anticoagulation for 6-month recanalization rates. CONCLUSIONS: This network meta-analysis evaluates the outcomes in CVT treatment, comparing standard anticoagulation, DOACs, and EVT, with evidence that DOACs have similar outcomes to standard anticoagulation in the treatment of CVT. EVT resulted in an increased risk of overall mortality but improved 6-month recanalization rates.