Leukocyte differential gene expression prognostic value for high versus low seizure frequency in temporal lobe epilepsy.

BACKGROUND: This study was performed to test the hypothesis that systemic leukocyte gene expression has prognostic value differentiating low from high seizure frequency refractory temporal lobe epilepsy (TLE). METHODS: A consecutive series of patients with refractory temporal lobe epilepsy was studied. Based on a median baseline seizure frequency of 2.0 seizures per month, low versus high seizure frequency was defined as ≤ 2 seizures/month and > 2 seizures/month, respectively. Systemic leukocyte gene expression was analyzed for prognostic value for TLE seizure frequency. All differentially expressed genes were analyzed, with Ingenuity® Pathway Analysis (IPA®) and Reactome, to identify leukocyte gene expression and biological pathways with prognostic value for seizure frequency. RESULTS: There were ten males and six females with a mean age of 39.4 years (range: 16 to 62 years, standard error of mean: 3.6 years). There were five patients in the high and eleven patients in the low seizure frequency cohorts, respectively. Based on a threshold of twofold change (p < 0.001, FC > 2.0, FDR < 0.05) and expression within at least two pathways from both Reactome and Ingenuity® Pathway Analysis (IPA®), 13 differentially expressed leukocyte genes were identified which were all over-expressed in the low when compared to the high seizure frequency groups, including NCF2, HMOX1, RHOB, FCGR2A, PRKCD, RAC2, TLR1, CHP1, TNFRSF1A, IFNGR1, LYN, MYD88, and CASP1. Similar analysis identified four differentially expressed genes which were all over-expressed in the high when compared to the low seizure frequency groups, including AK1, F2R, GNB5, and TYMS. CONCLUSIONS: Low and high seizure frequency TLE are predicted by the respective upregulation and downregulation of specific leukocyte genes involved in canonical pathways of neuroinflammation, oxidative stress and lipid peroxidation, GABA (γ-aminobutyric acid) inhibition, and AMPA and NMDA receptor signaling. Furthermore, high seizure frequency-TLE is distinguished prognostically from low seizure frequency-TLE by differentially increased specific leukocyte gene expression involved in GABA inhibition and NMDA receptor signaling. High and low seizure frequency patients appear to represent two mechanistically different forms of temporal lobe epilepsy based on leukocyte gene expression.

Gene Expression Patterns Associated with Survival in Glioblastoma.

The aim of this study was to investigate gene expression alterations associated with overall survival (OS) in glioblastoma (GBM). Using the Nanostring nCounter platform, we identified four genes (COL1A2, IGFBP3, NGFR, and WIF1) that achieved statistical significance when comparing GBM with non-neoplastic brain tissue. The four genes were included in a multivariate Cox Proportional Hazard model, along with age, extent of resection, and O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation, to create a unique glioblastoma prognostic index (GPI). The GPI score inversely correlated with survival: patient with a high GPI had a median OS of 7.5 months (18-month OS = 9.7%) whereas patients with a low GPI had a median OS of 20.1 months (18-month OS = 54.5%; log rank p-value = 0.004). The GPI score was then validated in 188 GBM patients from The Cancer Genome Atlas (TCGA) from a national data base; similarly, patients with a high GPI had a median OS of 10.5 months (18-month OS = 12.4%) versus 16.9 months (18-month OS = 41.5%) for low GPI (log rank p-value = 0.0003). We conclude that this novel mRNA-based prognostic index could be useful in classifying GBM patients into risk groups and refine prognosis estimates to better inform treatment decisions or stratification into clinical trials.

Peripheral Nerve Stimulation for Refractory Trigeminal Pain: Recent Single-Institution Case Series With Long-Term Follow-Up and Review of the Literature.

BACKGROUND: Peripheral neurostimulation (PNS) for medically refractory trigeminal pain is an emerging alternative to traditional surgical approaches, with safety and efficacy demonstrated in several retrospective series and a prospective trial currently in progress. Many existing studies suffer from relatively small numbers and short or inconsistent follow-up, making balanced treatment assessment difficult. MATERIALS AND METHODS: Consecutive cases of trial and permanent placement of trigeminal branch stimulation electrodes by a single surgeon from May 2014 through January 2019 were retrospectively reviewed from a prospectively collected database, following the PROCESS guidelines for surgical case series. Outcomes were assessed at six months and at last follow-up. RESULTS: Ninteen patients underwent trial electrode placement, with 15 patients undergoing permanent system placement. The most common diagnoses were idiopathic trigeminal neuralgia Type 2 (N = 8) and trigeminal neuropathic pain (N = 7). Median follow-up was 14 months (range 6-58 months). At last follow-up, 12 of 15 implanted patients (80%) were still receiving stimulation, with mean (median) pain reduction of 52.3% (47.5%). Infection and revision rates were high, although erosion and migration, which have typically plagued trigeminal PNS surgery, did not occur. Implanted systems were well-tolerated, with excellent cosmetic outcomes and high patient satisfaction that proved durable over long follow-up. CONCLUSIONS: We present a single-institution series of PNS for complex craniofacial pain involving the trigeminal nerve. The procedure is safe, effective and durable over at least one year in the large majority of a well-selected patient population.

Cortical gene expression: prognostic value for seizure outcome following temporal lobectomy and amygdalohippocampectomy.

Whole genome analyses were performed to test the hypothesis that temporal cortical gene expression differs between epilepsy patients rendered seizure-free versus non-seizure-free following anterior temporal lobectomy with amygdalohippocampectomy (ATL/AH). Twenty four patients underwent ATL/AH to treat medically intractable seizures of temporal lobe origin (mean age 35.5 years, mean follow-up 42.2 months); they were then dichotomized into seizure-free and non-seizure-free groups. Tissue RNA was isolated from the lateral temporal cortex and gene expression analysis was performed. Whole genome data were analyzed for prognostic value for seizure-free outcome following ATL/AH by logistic regression. Genes that could distinguish seizure outcome groups were identified based on providing an accuracy of >0.90 judging by area under the receiver operating characteristic curve, AUC, with a P value of the slope coefficient of <0.05. Four genes and seven RNA probes were with prognostic value for post-operative seizure-free outcome. Gene expression associated with seizure-free outcome included relative down-regulation of zinc finger protein 852 (ZNF852), CUB domain-containing protein 2 (CDCP2), proline-rich transmembrane protein 1 (PRRT1), hypothetical LOC440200 (FLJ41170), RNA probe 8047763, RNA probe 8126238, RNA probe 8113489, RNA probe 8092883, RNA probe 7935228, RNA probe 806293, and RNA probe 8104131. This study describes the predictive value of temporal cortical gene expression for seizure-free outcome after ATL/AH. Four genes and seven RNA probes were found to predict post-operative seizure-free outcome. Future prospective investigation of these genes and probes in human brain tissue and blood could establish new biomarkers predictive of seizure outcome following ATL/AH.

Cortical gene expression correlates of temporal lobe epileptogenicity.

INTRODUCTION: Despite being one of the most common neurological diseases, it is unknown whether there may be a genetic basis to temporal lobe epilepsy (TLE). Whole genome analyses were performed to test the hypothesis that temporal cortical gene expression differs between TLE patients with high vs. low baseline seizure frequency. METHODS: Baseline seizure frequency was used as a clinical measure of epileptogenicity. Twenty-four patients in high or low seizure frequency groups (median seizures/month) underwent anterior temporal lobectomy with amygdalohippocampectomy for intractable TLE. RNA was isolated from the lateral temporal cortex and submitted for expression analysis. Genes significantly associated with baseline seizure frequency on likelihood ratio test were identified based on >0.90 area under the ROC curve, P value of <0.05. RESULTS: Expression levels of forty genes were significantly associated with baseline seizure frequency. Of the seven most significant, four have been linked to other neurologic diseases. Expression levels associated with high seizure frequency included low expression of Homeobox A10, Forkhead box A2, Lymphoblastic leukemia derived sequence 1, HGF activator, Kelch repeat and BTB (POZ) domain containing 11, Thanatos-associated protein domain containing 8 and Heparin sulfate (glucosamine) 3-O-sulfotransferase 3A1. CONCLUSIONS: This study describes novel associations between forty known genes and a clinical marker of epileptogenicity, baseline seizure frequency. Four of the seven discussed have been previously related to other neurologic diseases. Future investigation of these genes could establish new biomarkers for predicting epileptogenicity, and could have significant implications for diagnosis and management of temporal lobe epilepsy, as well as epilepsy pathogenesis.

Brain tumors enhance plasmatic coagulation: the role of hemeoxygenase-1.

BACKGROUND: Patients with brain tumors suffer significant thrombotic morbidity and mortality. In addition to increased thrombin generation via tumor release of tissue factor-bearing microparticles and hyperfibrinogenemia, brain tumors and surrounding normal brain likely generate endogenous carbon monoxide (CO) via the hemeoxygenase-1 (HO-1) system. CO has been shown to enhance plasmatic coagulation via formation of carboxyhemefibrinogen (COHF). Thus, our goals in this study were to determine whether patients with brain tumors had increased HO-1 upregulation/CO production, plasmatic hypercoagulability, and formation of COHF. METHODS: Patients with brain tumors (N = 20) undergoing craniotomy had blood collected for determination of carboxyhemoglobin as a marker of HO-1 activity, plasmatic hypercoagulability (defined as clot strength > 95% confidence interval value of normal subject plasma), and COHF formation (determined with a thrombelastograph-based assay). Plasma obtained from commercially available normal subjects (N = 30) was used for comparison with brain tumor patient samples. RESULTS: Brain tumor patients had carboxyhemoglobin concentrations of 1.5% ± 0.5% (mean ± SD), indicative of HO-1 upregulation. Compared with normal subject plasma, brain tumor patient plasma had significantly (P < 0.0001) greater clot formation velocity (5.2 ± 1.5 vs 9.5 ± 2.3 dynes/cm/s, respectively) and significantly (P = 0.00016) stronger final clot strength (166 ± 28 vs 230 ± 78 dynes/cm, respectively). Ten of the brain tumor patients had plasma clot strength that exceeded the 95% confidence interval value observed in normal subjects, and 12 of the brain tumor patients had COHF formation. Five of the brain tumor patients in the hypercoagulable subgroup had COHF formation. Last, 5 of the hypercoagulable patients had primary brain tumors, whereas the other 5 patients had metastatic tumors or an inflammatory mass lesion. CONCLUSIONS: A subset of patients with brain tumors has increased endogenous CO production, plasmatic hypercoagulability, and COHF formation. Future investigation of the role played by HO-1 derived CO in the pathogenesis of brain tumor-associated thrombophilia is warranted.

Discontinuation of affirmative action: Consequences for black educational equity, neurosurgical residency, and medical diversity, with consideration of potential adversity as a new path forward.

Background: The underrepresentation of the Black community in neurosurgery is concerning, especially given projections that racial minorities will become the majority in the U.S. by 2044. Yet, despite these forecasts, Black candidates make up less than 4% of those in neurosurgical training programs. The recent Supreme Court decision to end Affirmative Action underscores the urgency of addressing this disparity. This research delves into the implications of eliminating Affirmative Action on neurosurgery admissions and residencies. Methods: A comprehensive literature search was performed using PubMed, OVID Embase, and OVID Medline, employing the keywords "Black", "Neurosurgery", and "Residency". The Maslow Adversity Index (MAI) was created to integrate adversity as a factor in neurosurgery residency evaluation. Results: After Affirmative Action, Black college enrollment increased, peaking at 36% by 2020. However, Black medical students remain underrepresented in neurosurgery residencies. ALDC (Athletes, Legacies, Dean's List, Children of faculty/staff) admissions criteria favor White students. Furthermore, studies have highlighted the beneficial impacts of racial concordance on patient outcomes. The end of Affirmative Action necessitates new diversity strategies in admissions. A points-based assessment, inspired by Maslow's hierarchy, recognizes adversities faced by underrepresented applicants which could help residency programs enhance diversity, inclusivity, and equity in selection. Conclusion: Despite the growth in Black college attendance, disparities persist in specialized medical fields like neurosurgery. The end to Affirmative Action policies might exacerbate these disparities. Embracing holistic admission approaches, rooted in Maslow's hierarchy. This consideration is key for inclusive representation, impacting education, professions, and health outcomes.

Addressing healthcare disparities in homeless neurosurgical patients: A comprehensive literature review on strategies for equitable care and improved outcomes.

Background: Homelessness is a growing concern in the US, with 3.5 million people experiencing it annually and 600,000 on any given night. Homeless individuals face increased vulnerability to 30-day hospital readmissions and higher mortality rates, straining the healthcare system and exacerbating existing disparities. This study aims to inform neurosurgeons on evidence-based strategies to reduce readmission and mortality rates among homeless patients by reviewing the literature on the impact of medical respite on 30-day readmission rates. The study aims to gauge the efficacy of medical respite in reducing hospital readmissions and improving health outcomes for homeless individuals. Methods: A comprehensive literature search was conducted across PubMed, Embase/Medline, and Cochrane databases, as well as consulting the National Institute for Medical Respite Care and the Department of Health Care Access and Information. Ten articles were chosen from an initial 296 to investigate the impact of respite programs on readmission rates among homeless patients. Results: Homeless patients experience high readmission rates due to various factors. Interventions such as respite programs and a comprehensive approach to healthcare can lower these rates. Collaboration between hospitals and medical respites has proven particularly effective. Conclusion: Inadequate healthcare for homeless individuals leads to increased readmissions, longer hospital stays, and higher costs. Medical respites are a viable solution, but limited resources hamper their effectiveness. Therefore, it is crucial to facilitate cooperation between hospitals, respites, and other entities. Future research should focus on disparity in neurosurgical procedures and explore alternative services. An interdisciplinary approach is key to addressing healthcare inequalities.

Utility of Diffusion Tensor Imaging in Preterm Infants with Germinal Matrix Hemorrhage and Intraventricular Hemorrhage: A Systematic Review.

OBJECTIVE: Intraventricular hemorrhage (IVH) and germinal matrix hemorrhage (GMH) are the most common brain injuries in preterm infants. Neonates with these injuries are at greater risk of impaired neurodevelopmental outcome. Current guidelines recommend screening infants with cranial ultrasound (CUS); however, this is prone to missing subtle injury patterns, particularly within the posterior fossa. The present report sought to discuss the utility of diffusion tensor imaging (DTI) in preterm infants. METHODS: A systematic review of PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included manuscripts were methodically scrutinized for quality, DTI use, and neurologic outcome. RESULTS: Twenty studies with 1574 infants who underwent DTI were included. There were 574 preterm infants with GMH-IVH on DTI. Twelve studies documented decreased fractional anisotropy, whereas 6 demonstrated structural segregation and asymmetrical white matter myelination in these infants. Seven studies documented concurrent CUS use with 2 studies comparing DTI findings with CUS findings. In both studies, DTI more accurately detected presence of GMH, especially within the cerebellum. Among GMH-IVH preterm infants, 58.5% demonstrated cognitive, intellectual, and language delays at follow-up (mean, 32.4 months). Additionally, lower fractional anisotropy values on initial DTI were associated with cognitive, language, and motor delays. CONCLUSIONS: Although DTI is more sensitive for picking up subtle injury patterns, CUS remains the standard of care when screening for injuries that would necessitate surgical intervention. DTI offers a refined understanding of the sequelae of GMH-IVH with microstructural changes found on DTI being associated with childhood motor and cognitive outcomes.

Redefining cerebellar assessment: A comprehensive review of the cerebellum's cognitive and affective roles and the efficacy of CCAS scales.

Background: Emerging research expands our understanding of the cerebellum beyond motor control to include cognitive, emotional, and autonomic functions. This review examines the cerebellum's complex role, spotlighting Schmahmann's syndrome, or cerebellar cognitive affective syndrome (CCAS), which impairs executive functions, language, and spatial processing. It emphasizes advancements in diagnosing CCAS and the imperative of developing superior diagnostic tools for managing cerebellar pathologies effectively. Methods: A comprehensive literature search was performed using databases such as PubMed, OVID Embase, and OVID Medline. Using the keywords "cerebellar cognitive, affective syndrome" and "Schmahmann syndrome," the search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines for systemic review, in which the selection process narrowed down an initial set of 54 articles to 12, focusing on the impact of the CCAS scale on diagnosing and understanding Schmahmann's syndrome. Results: The review's analysis confirms the cerebellum's roles in motor and cognitive functions and underscores the CCAS scale as a significant advancement in detecting cerebellar deficits, surpassing traditional assessments such as the mini-mental state examination and Montreal cognitive assessment. Conclusion: This review emphasizes the importance of understanding the cerebellum's involvement in cognition and emotion and the crucial role of the CCAS scale for identifying cerebellar impairments. It calls for better diagnostic tools to assess CCAS accurately and suggests enhancing the CCAS Scale to reflect cultural and educational diversity. This will improve the diagnosis and treatment of cerebellar disorders, promoting a comprehensive neurological perspective on the cerebellum's functions.

Awake neurosurgery: Advancements in microvascular decompression for trigeminal neuralgia.

Background: The treatment landscape for trigeminal neuralgia (TN) involves various surgical interventions, among which microvascular decompression (MVD) stands out as highly effective. While MVD offers significant benefits, its success relies on precise surgical techniques and patient selection. In addition, the emergence of awake surgery techniques presents new opportunities to improve outcomes and minimize complications associated with MVD for TN. Methods: A thorough review of the literature was conducted to explore the effectiveness and challenges of MVD for TN, as well as the impact of awake surgery on its outcomes. PubMed and Medline databases were searched from inception to March 2024 using specific keywords "Awake Neurosurgery," "Microvascular Decompression," AND "Trigeminal Neuralgia." Studies reporting original research on human subjects or preclinical investigations were included in the study. Results: This review highlighted that MVD emerges as a highly effective treatment for TN, offering long-term pain relief with relatively low rates of recurrence and complications. Awake surgery techniques, including awake craniotomy, have revolutionized the approach to MVD, providing benefits such as reduced postoperative monitoring, shorter hospital stays, and improved neurological outcomes. Furthermore, awake MVD procedures offer opportunities for precise mapping and preservation of critical brain functions, enhancing surgical precision and patient outcomes. Conclusion: The integration of awake surgery techniques, particularly awake MVD, represents a significant advancement in the treatment of TN. Future research should focus on refining awake surgery techniques and exploring new approaches to optimize outcomes in MVD for TN.

Subdural hematoma, retinal hemorrhage, and fracture triad as a clinical predictor for the diagnosis of child abuse.

OBJECTIVE: Nonaccidental trauma (NAT) is a major cause of traumatic death during infancy and early childhood. Several findings are known to raise the index of clinical suspicion: subdural hematoma (SDH), retinal hemorrhage (RH), fracture, and external trauma. Combinations of certain injury types, determined via statistical frequency associations, may assist clinical diagnostic tools when child abuse is suspected. The present study sought to assess the statistical validity of the clinical triad (SDH + RH + fracture) in the diagnosis of child abuse and by extension pediatric NAT. METHODS: A retrospective review of The University of Arizona Trauma Database was performed. All patients were evaluated for the presence or absence of the components of the clinical triad according to specific International Classification of Diseases (ICD)-10 codes. Injury type combinations included some variation of SDH, RH, all fractures, noncranial fracture, and cranial fracture. Each injury type was then correlated with the ICD-10 codes for child abuse or injury comment keywords. Statistical analysis via contingency tables was then conducted for test characteristics such as sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: There were 3149 patients younger than 18 years of age included in the quantitative analysis, all of whom had at least one component of the clinical triad. From these, 372 patients (11.8%) had a diagnosis of child abuse. When compared to a single diagnosis of either SDH, RH, all fractures, noncranial fracture, or cranial fracture, the clinical triad had a significantly greater correlation with the diagnosis of child abuse (100% of cases) (p < 0.0001). The dyad of SDH + RH also had a significantly greater correlation with a child abuse diagnosis compared to single diagnoses (88.9%) (p < 0.0001). The clinical triad of SDH + RH + fracture had a sensitivity of 88.8% (95% CI 87.6%-89.9%), specificity of 100% (95% CI 83.9%-100%), and positive predictive value of 100% (95% CI 99.9%-100%). The dyad of SDH + RH had a sensitivity of 89.1% (95% CI 87.9%-90.1%), specificity of 88.9% (95% CI 74.7%-95.6%), and positive predictive value of 99.9% (95% CI 99.6%-100%). All patients with the clinical triad were younger than 3 years of age. CONCLUSIONS: When SDH, RH, and fracture were present together, child abuse and by extension pediatric NAT were highly likely to have occurred.

The importance of behavioral interventions in traumatic brain injury.

Background: Traumatic brain injury (TBI) poses a significant public health concern, profoundly impacting individuals and society. In this context, behavioral interventions have gained prominence as crucial elements in TBI management, addressing the diverse needs of TBI-affected individuals. Methods: A comprehensive literature search was conducted, utilizing databases such as PubMed, Embase, and Scopus. Inclusion criteria encompassed studies focusing on behavioral interventions in TBI, with a particular emphasis on their impact on outcomes. Relevant articles published within the past decade were prioritized, and a qualitative synthesis of the findings was performed. Results: Behavioral interventions have demonstrated their effectiveness in addressing various aspects of TBI care. They have been instrumental in improving cognitive functions, emotional stability, and adaptive behaviors among TBI patients. However, it is important to acknowledge that challenges still exist, including issues related to clinical heterogeneity and healthcare disparities. Conclusion: The integration of behavioral interventions into standard clinical practice marks a transformative shift in TBI care. This approach holds immense potential for enhancing patient outcomes and elevating the overall quality of life for individuals grappling with the complexities of this condition. This review serves as a clarion call for healthcare practitioners, researchers, and policymakers to recognize the pivotal role of behavioral interventions in TBI care, advocating for their wider adoption to advance the field toward a more holistic and patient-centric approach.

Neuroprotection strategies in traumatic brain injury: Studying the effectiveness of different clinical approaches.

Background: This review delves into clinical strategies aimed at addressing the complexities of traumatic brain injury (TBI), specifically focusing on pharmaceutical interventions and stem cell therapies as potential avenues for enhancing TBI outcomes. Methods: A thorough review of clinical strategies for TBI management, encompassing pharmaceutical and nonpharmaceutical interventions, was performed. PubMed, MEDLINE and clinical trial databases were searched to identify relevant studies and clinical trials. Inclusion criteria consisted of studies involving pharmaceutical agents and other clinical approaches (i.e., stem cell therapies) targeting neuroinflammation, excitotoxicity, oxidative stress, and neurodegeneration in TBI. Data from clinical trials and ongoing research initiatives were analyzed to assess the current status and potential of these clinical approaches. Results: Many trials have been conducted to face the challenge that is TBI. These interventions are designed to target critical aspects of secondary brain injury, encompassing neuroinflammation, excitotoxicity, oxidative stress, and neurodegeneration. Despite this, there is no panacea or definitive remedy for this condition. Combining therapies in a patient-tailored approach seems to be our best chance to improve these patients' outcomes, but systematic protocols are needed. Conclusion: Clinical strategies represent dynamic and continually evolving pathways in TBI management. This review provides an extensive overview of the existing landscape of clinical approaches and promising new studies and outlines their influence on patient outcomes. By highlighting challenges and presenting opportunities, it contributes to the ongoing mission to advance clinical care for individuals impacted by TBI.

Neuroprotection: Surgical approaches in traumatic brain injury.

Background: This review is centered on the pivotal role of surgical interventions within the comprehensive management of traumatic brain injury (TBI). Surgical strategies are indispensable components of TBI care, encompassing primary injury management and the alleviation of secondary injury processes, including the handling of intracranial hemorrhages (ICHs), contusions, and mass lesions. Methods: A systematic review was carried out by searching databases including PubMed, Embase, and Scopus. The inclusion criteria involved studies discussing surgical strategies for TBI, with a focus on primary injury management, ICHs, contusions, and mass lesions. More recent articles were prioritized, and data were synthesized to assess the impact of surgical interventions on TBI outcomes. Results: The evolution of surgical technologies has heralded a transformation in TBI management. These advancements encompass minimally invasive procedures, neuroimaging-guided surgeries, and robotic-assisted techniques, all geared toward optimizing patient outcomes. Conclusion: Surgical interventions within TBI care present unique challenges, such as timing considerations, patient selection criteria, and postoperative care. This review underscores the critical significance of multidisciplinary collaboration among neurosurgeons, neurologists, and critical care specialists. Such collaboration is essential to tailor surgical strategies to the individualized needs of patients. Moreover, the review highlights emerging trends in TBI surgery and underscores the ongoing imperative of research endeavors aimed at refining surgical protocols and ultimately enhancing patient outcomes.

Neuromodulation and the Gut-Brain Axis: Therapeutic Mechanisms and Implications for Gastrointestinal and Neurological Disorders.

The gut-brain axis (GBA) represents a complex, bidirectional communication network that intricately connects the gastrointestinal tract with the central nervous system (CNS). Understanding and intervening in this axis opens a pathway for therapeutic advancements for neurological and gastrointestinal diseases where the GBA has been proposed to play a role in the pathophysiology. In light of this, the current review assesses the effectiveness of neuromodulation techniques in treating neurological and gastrointestinal disorders by modulating the GBA, involving key elements such as gut microbiota, neurotrophic factors, and proinflammatory cytokines. Through a comprehensive literature review encompassing PubMed, Google Scholar, Web of Science, and the Cochrane Library, this research highlights the role played by the GBA in neurological and gastrointestinal diseases, in addition to the impact of neuromodulation on the management of these conditions which include both gastrointestinal (irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and gastroesophageal reflux disease (GERD)) and neurological disorders (Parkinson's disease (PD), Alzheimer's disease (AD), autism spectrum disorder (ASD), and neuropsychiatric disorders). Despite existing challenges, the ability of neuromodulation to adjust disrupted neural pathways, alleviate pain, and mitigate inflammation is significant in improving the quality of life for patients, thereby offering exciting prospects for future advancements in patient care.

Curcuminoids limit neutrophil-mediated reperfusion injury in experimental stroke by targeting the endothelium.

OBJECTIVE: We sought to test the hypothesis that turmeric-derived curcuminoids limit reperfusion brain injury in an experimental model of stroke via blockade of early microvascular inflammation during reperfusion. METHODS: Male Sprague Dawley rats subjected to MCAO/R were treated with turmeric-derived curcuminoids (vs. vehicle) 1 hour prior to reperfusion (300 mg/kg ip). Neutrophil adhesion to the cerebral microcirculation and measures of neutrophil and endothelial activation were assayed during early reperfusion (0-4 hours); cerebral infarct size, edema, and neurological function were assessed at 24 hours. Curcuminoid effects on TNFα-stimulated human brain microvascular endothelial cell (HBMVEC) were assessed. RESULTS: Early during reperfusion following MCAO, curcuminoid treatment decreased neutrophil rolling and adhesion to the cerebrovascular endothelium by 76% and 67% and prevented >50% of the fall in shear rate. The increased number and activation state (CD11b and ROS) of neutrophils were unchanged by curcuminoid treatment, while increased cerebral expression of TNFα and ICAM-1, a marker of endothelial activation, were blocked by >30%. Curcuminoids inhibited NF-κB activation and subsequent ICAM-1 gene expression in HBMVEC. CONCLUSION: Turmeric-derived curcuminoids limit reperfusion injury in stroke by preventing neutrophil adhesion to the cerebrovascular microcirculation and improving shear rate by targeting the endothelium.

Chemotactic and mitogenic stimuli of neuronal apoptosis in patients with medically intractable temporal lobe epilepsy.

To identify the upstream signals of neuronal apoptosis in patients with medically intractable temporal lobe epilepsy (TLE), we evaluated by immunohistochemistry and confocal microscopy brain tissues of 13 TLE patients and 5 control patients regarding expression of chemokines and cell-cycle proteins. The chemokine RANTES (CCR5) and other CC-chemokines and apoptotic markers (caspase-3, -8, -9) were expressed in lateral temporal cortical and hippocampal neurons of TLE patients, but not in neurons of control cases. The chemokine RANTES is usually found in cytoplasmic and extracellular locations. However, in TLE neurons, RANTES was displayed in an unusual location, the neuronal nuclei. In addition, the cell-cycle regulatory transcription factor E2F1 was found in an abnormal location in neuronal cytoplasm. The pro-inflammatory enzyme cyclooxygenase-2 and cytokine interleukin-1ß were expressed both in neurons of patients suffering from temporal lobe epilepsy and from cerebral trauma. The vessels showed fibrin leakage, perivascular macrophages and expression of IL-6 on endothelial cells. In conclusion, the cytoplasmic effects of E2F1 and nuclear effects of RANTES might have novel roles in neuronal apoptosis of TLE neurons and indicate a need to develop new medical and/or surgical neuroprotective strategies against apoptotic signaling by these molecules. Both RANTES and E2F1 signaling are upstream from caspase activation, thus the antagonists of RANTES and/or E2F1 blockade might be neuroprotective for patients with medically intractable temporal lobe epilepsy. The results have implications for the development of new medical and surgical therapies based on inhibition of chemotactic and mitogenic stimuli of neuronal apoptosis in patients with medically intractable temporal lobe epilepsy.

Surgical treatment of superimposed, lower extremity, peripheral nerve entrapments with diabetic and idiopathic neuropathy.

BACKGROUND: Although it is recognized that people with peripheral neuropathy have an increased prevalence of chronic nerve entrapment, controversy still exists over their management. The present report details the evaluation, surgical approach, and outcome of a large cohort of people with diabetic and with idiopathic neuropathy. METHODS: A retrospective review of 158 consecutive patients, 96 with diabetic and 62 with idiopathic neuropathy, was done to analyze the results of neurolysis of multiple sites of chronic nerve compression in the lower extremity. Of these patients, 50 had a contralateral limb decompressed for a total of 208 limbs included in the study. Outcomes included visual analog scale (VAS) for pain in the 109 patients who had pain level greater than 8.0, measurement of the cutaneous pressure threshold for sensibility, self-reported change in pain medication usage, and self-reported change in balance. RESULTS: With a minimum follow-up of 1 year, 88% of patients with preoperative numbness reported improvement in sensation (P < 0.001). Of the 84 patients with impaired balance, 81% reported improvement in balance. Of those whose VAS was greater than 8, 83% reported an improvement in VAS (P < 0.001). There was a concomitant reduction in pain medication usage. There was no difference in outcomes between patients with diabetic versus idiopathic neuropathy in response to nerve decompression. CONCLUSIONS: Neurolysis of lower extremity chronic nerve compressions in patients with neuropathy and superimposed nerve compressions is an effective method for relieving pain, restoring sensation, and improving balance.

Emotional intelligence in neurosurgery: Mitigating burnout and enhancing performance.

Background: This study underscores the high burnout rates among physicians, particularly surgical residents, attributing it to the demanding health-care ecosystem. It highlights the negative impacts of burnout, such as medical errors and increased health-care costs, while exploring the potential mitigating role of emotional intelligence (EI) and mindfulness. The research aimed to analyze the existing literature on EI in neurosurgery, focusing on its relationship with physician burnout and its potential role in healthcare leadership and residency training programs. Methods: A comprehensive literature review was conducted using multiple databases, including PubMed, OVID Embase, and OVID Medline, using the keywords "Emotional Intelligence" and "neurosurgery." The search duration spanned from each database's inception to June 2023. Results: The review highlighted various studies emphasizing the importance of integrating EI and mindfulness training into medical education and leadership, suggesting that a balance between technical competencies and interpersonal skills are critical. It identified personal integrity, effective communication, professional ethics, pursuit of excellence, relationship building, and critical thinking as key competencies for health-care leadership. Conclusion: EI and a growth mindset play a critical role in managing burnout, enhancing job satisfaction and performance, and promoting effective healthcare leadership. The review, however, acknowledges certain limitations such as small sample sizes, single-institution experiences, potential biases, and inconsistencies in burnout parameters and EI measurement tools. Despite these, it points toward potential areas for future investigation and highlights the importance of standardized EI measurement tools and robust quantitative assessment methods.