Augmented surgical decision-making for glioblastoma: integrating AI tools into education and practice.

Surgical decision-making for glioblastoma poses significant challenges due to its complexity and variability. This study investigates the potential of artificial intelligence (AI) tools in improving "decision-making processes" for glioblastoma surgery. A systematic review of literature identified 10 relevant studies, primarily focused on predicting resectability and surgery-related neurological outcomes. AI tools, especially rooted in radiomics and connectomics, exhibited promise in predicting resection extent through precise tumor segmentation and tumor-network relationships. However, they demonstrated limited effectiveness in predicting postoperative neurological due to dynamic and less quantifiable nature of patient-related factors. Recognizing these challenges, including limited datasets and the interpretability requirement in medical applications, underscores the need for standardization, algorithm optimization, and addressing variability in model performance and then further validation in clinical settings. While AI holds potential, it currently does not possess the capacity to emulate the nuanced decision-making process utilized by experienced neurosurgeons in the comprehensive approach to glioblastoma surgery.

A Scalable Histological Method to Embed and Section Multiple Brains Simultaneously.

The preparation and processing of rodent brains for evaluation by immunohistochemistry is time-consuming. A large number of mouse brains are routinely used in experiments in neuroscience laboratories to evaluate several models of human diseases. Thus, methods are needed to reduce the time associated with processing brains for histology. A scalable method was developed to embed, section, and stain multiple mouse brains using supplies found in any common histology laboratory. Section collection schemes can be scaled to provide identical bregma locations between adjacent sections for immunohistochemistry, facilitating comprehensive, high-quality immunohistochemistry. As a result, sectioning and staining times are considerably reduced as sections from multiple blocks are stained simultaneously. This method improves on previous procedures and allows multiple embedding and subsequent immunostaining of brains easily with a dramatically reduced time requirement. Furthermore, we expand this method for use in numerous mouse tissues, rat brain tissue, and post-mortem human brain and arterial tissues. In summary, this procedure allows the processing of many rodent or human tissues from perfusion through microscopy in 10 days or less.

Focused ultrasound as a treatment modality for gliomas.

Ultrasound waves were initially used as a diagnostic tool that provided critical insights into several pathological conditions (e.g., gallstones, ascites, pneumothorax, etc.) at the bedside. Over the past decade, advancements in technology have led to the use of ultrasound waves in treating many neurological conditions, such as essential tremor and Parkinson's disease, with high specificity. The convergence of ultrasound waves at a specific region of interest/target while avoiding surrounding tissue has led to the coined term "focused ultrasound (FUS)." In tumor research, ultrasound technology was initially used as an intraoperative guidance tool for tumor resection. However, in recent years, there has been growing interest in utilizing FUS as a therapeutic tool in the management of brain tumors such as gliomas. This mini-review highlights the current knowledge surrounding using FUS as a treatment modality for gliomas. Furthermore, we discuss the utility of FUS in enhanced drug delivery to the central nervous system (CNS) and highlight promising clinical trials that utilize FUS as a treatment modality for gliomas.

Nutritional Support Following Traumatic Brain Injury: A Comprehensive Review.

Traumatic brain injury (TBI) can contribute to extensive dysbiosis of the gastrointestinal system, leading to worsened outcomes. The importance of nutrition in recovery is underappreciated but highly important. In this focused review, we discuss the timing of nutritional interventions with supporting data. We highlight routes of administration that are important given the extent of injury often seen in TBI. The increased energy demands can be met through these approaches. Furthermore, patients need increased vitamins, minerals, and supplements. These interventions are constantly being refined. The current standards are reviewed with an emphasis on evidence-based practices.

Neurocognitive Sequelae and Rehabilitation after Subarachnoid Hemorrhage: Optimizing Outcomes.

Subarachnoid hemorrhage (SAH) is a medical emergency that requires immediate intervention. The etiology varies between cases; however, rupture of an intracranial aneurysm accounts for 80% of medical emergencies. Early intervention and treatment are essential to prevent long-term complications. Over the years, treatment of SAH has drastically improved, which is responsible for the rapid rise in SAH survivors. Post-SAH, a significant number of patients exhibit impairments in memory and executive function and report high rates of depression and anxiety that ultimately affect daily living, return to work, and quality of life. Given the rise in SAH survivors, rehabilitation post-SAH to optimize patient outcomes becomes crucial. The review addresses the current rehabilitative strategies to combat the neurocognitive and behavioral issues that may arise following SAH.

Pain Management During West Virginia's Opioid Crisis.

PURPOSE: Opioid use disorder has caused significant morbidity and mortality resulting in opioid prescribing limiting laws, such as State Bill 273 in West Virginia. The purpose of this study is to explore the impacts of a restrictive opioid prescription law on physicians in medical practice in West Virginia. METHODS: A qualitative study with open-ended semistructured interviews with a purposive sample of physicians in West Virginia. Interviews were recorded and transcribed verbatim. A preliminary code book was developed by 3 coinvestigators. Interview transcriptions were analyzed with a code-based text search query. Content analysis was utilized as the methodological orientation underpinning for the current work. RESULTS: Interviews were conducted with 20 physicians (10 primary care physicians and 10 specialty physicians) in practice in West Virginia. Physicians identified 5 theoretical domains related to SB273: changing opioid prescribing and documentation requirements; rural socioeconomic disparities; a continuum between chronic pain and substance use disorder; difficulty in balancing patient needs and the concern for diversion; lack of available alternatives to opioids for chronic. CONCLUSION: Prescribing opioids in rural West Virginia is complex due to identified challenges. Recommendations for opioids prescribing legislation include clear messaging of guidelines and recommendations, efforts to address socioeconomic disparities of health and pain, and improved accessibility for treatment of both pain and dependence in rural communities are important areas of growth in the rural health care environment.

Myelin oligodendrocyte glycoprotein antibody-associated optic neuritis and myelitis in COVID-19: a case report and a review of the literature.

Background: Our case explored the spectrum of autoimmune and infectious neurological complications of Coronavirus Disease 2019. In addition, we also reviewed and discussed clinical features, neuroimaging, CSF findings, and outcomes in patients with COVID-19-associated Myelin Oligodendrocyte Glycoprotein Antibody Disorder (MOGAD) CNS inflammatory disorder. Case presentation: Here we presented a case of post-Coronavirus Disease 2019 infection Myelin Oligodendrocyte Glycoprotein Antibody Disorder in a 41-year-old male who presented with gait instability, urinary retention, and confusion. Workup done in hospital showed transverse myelitis in cervical spine region and left optic neuritis. Laboratory findings showed Myelin Oligodendrocyte Glycoprotein-IgG antibodies were positive in serum (1:100), suggestive of post-COVID Myelin Oligodendrocyte Glycoprotein Antibody Disorder. Conclusion: To our knowledge, this is the first comprehensive case report and the literature review that includes the clinical features, neuroimaging, CSF findings, and outcomes in COVID-19-associated Myelin Oligodendrocyte Glycoprotein Antibody Disorder.

Pediatric Traumatic Brain Injury: An Update on Preclinical Models, Clinical Biomarkers, and the Implications of Cerebrovascular Dysfunction.

Traumatic brain injury (TBI) is a leading cause of pediatric morbidity and mortality. Recent studies suggest that children and adolescents have worse post-TBI outcomes and take longer to recover than adults. However, the pathophysiology and progression of TBI in the pediatric population are studied to a far lesser extent compared to the adult population. Common causes of TBI in children are falls, sports/recreation-related injuries, non-accidental trauma, and motor vehicle-related injuries. A fundamental understanding of TBI pathophysiology is crucial in preventing long-term brain injury sequelae. Animal models of TBI have played an essential role in addressing the knowledge gaps relating to pTBI pathophysiology. Moreover, a better understanding of clinical biomarkers is crucial to diagnose pTBI and accurately predict long-term outcomes. This review examines the current preclinical models of pTBI, the implications of pTBI on the brain's vasculature, and clinical pTBI biomarkers. Finally, we conclude the review by speculating on the emerging role of the gut-brain axis in pTBI pathophysiology.

Inflammation and the role of infection: Complications and treatment options following neurotrauma.

Traumatic brain injury can have devastating consequences for patients and extended hospital stays and recovery course. Recent data indicate that the initial insult causes profound changes to the immune system and leads to a pro-inflammatory state. This alteration in homeostasis predisposes patients to an increased risk of infection and underlying autoimmune conditions. Increased emphasis has been placed on understanding this process both in the clinical and preclinical literature. This review highlights the intrinsic inflammatory conditions that can occur within the initial hospital stay, discusses long-term immune consequences, highlights emerging treatment options, and delves into important pathways currently being investigated with preclinical models.

"The DEA would come in and destroy you": a qualitative study of fear and unintended consequences among opioid prescribers in WV.

BACKGROUND: West Virginia has one of the highest rates of opioid overdose related deaths and is known as the epicenter of the opioid crisis in the United States. In an effort to reduce opioid-related harms, SB 273 was signed in 2018, and aimed to restrict opioid prescribing in West Virginia. SB 273 was enacted during a time when physician arrests and convictions had been increasing for years and were becoming more prevalent and more publicized. This study aims to better understand the impact of the legislation on patients and providers. METHODS: Twenty semi-structured interviews were conducted with opioid-prescribing primary care physicians and specialists practicing throughout West Virginia. RESULTS: Four themes emerged, 1. Fear of disciplinary action, 2. Exacerbation of opioid prescribing fear due to restrictive legislation, 3. Care shifts and treatment gaps, and 4. Conversion to illicit substances. The clinicians recognized the harms of inappropriate prescribing and how this could affect their patients. Decreases in opioid prescribing were already occurring prior to the law implementation. Disciplinary actions against opioid prescribers resulted in prescriber fear, which was then exacerbated by SB 273 and contributed to shifts in care that led to forced tapering and opioid under-prescribing. Providers felt that taking on patients who legitimately required opioids could jeopardize their career. CONCLUSION: A holistic and patient-centered approach should be taken by legislative and disciplinary bodies to ensure patients are not abandoned when disciplinary actions are taken against prescribers or new legislation is passed.

Spectrum of Neuroimaging Findings in Post-COVID-19 Vaccination: A Case Series and Review of Literature.

Background and Purpose: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in Wuhan, China in December 2019. Symptoms range from mild flu-like symptoms to more severe presentations, including pneumonia, acute respiratory distress syndrome (ARDS), and even death. In response to the COVID-19 pandemic, the Emergency Use Authorization (EUA) approved the use of several vaccines. Because vaccines have been fast-tracked for emergency use, the short and long-term safety profile has been an area of concern. The aim of this paper is to extensively review published literature regarding post-COVID-19 vaccination neurological complications and characterize neuroimaging findings from three case presentations for early diagnosis and treatment. Methods: The analysis includes data from PubMed and Google Scholar. Articles included were retrieved from database inception beginning December 2020 with no language restrictions. Terms used include "SARS-CoV-2", "post Covid vaccination", "neurological complications", "Guillain-barre Syndrome", "Transverse-myelitis", "Cerebral Venous Sinus thrombosis", and "Cerebral hemorrhage". Results: The literature review yielded several neurological complications post vaccination, including cerebral sinus venous thrombosis, transverse myelitis, Guillain-Barré Syndrome and optic neuritis, to name a few. Patient case presentation findings were consistent with documented results in published literature. Conclusions: We present a case series with a thorough literature review documenting adverse neurological affects following COVID-19 vaccination. Our case presentations and literature review highlight the importance of neuroimaging when diagnosing post-COVID-19 vaccination adverse effects. MRI imaging study is an important tool to be considered in patients presenting with post-COVID-19 vaccination-related unexplained neurological symptoms for accurate diagnosis.

Tissue-Nonspecific Alkaline Phosphatase in Central Nervous System Health and Disease: A Focus on Brain Microvascular Endothelial Cells.

Tissue-nonspecific alkaline phosphatase (TNAP) is an ectoenzyme bound to the plasma membranes of numerous cells via a glycosylphosphatidylinositol (GPI) moiety. TNAP's function is well-recognized from earlier studies establishing its important role in bone mineralization. TNAP is also highly expressed in cerebral microvessels; however, its function in brain cerebral microvessels is poorly understood. In recent years, few studies have begun to delineate a role for TNAP in brain microvascular endothelial cells (BMECs)-a key component of cerebral microvessels. This review summarizes important information on the role of BMEC TNAP, and its implication in health and disease. Furthermore, we discuss current models and tools that may assist researchers in elucidating the function of TNAP in BMECs.

Mild traumatic brain injury increases vulnerability to cerebral ischemia in mice.

Recent studies have reported that TBI is an independent risk factor for subsequent stroke. Here, we tested the hypothesis that TBI would exacerbate experimental stroke outcomes via alternations in neuroimmune and neurometabolic function. We performed a mild closed-head TBI and then one week later induced an experimental stroke in adult male mice. Mice that had previously experienced TBI exhibited larger infarcts, greater functional deficits, and more pronounced neuroinflammatory responses to stroke. We hypothesized that impairments in central metabolic physiology mediated poorer outcomes after TBI. To test this, we treated mice with the insulin sensitizing drug pioglitazone (Pio) after TBI. Pio prevented the exacerbation of ischemic outcomes induced by TBI and also blocked the induction of insulin insensitivity by TBI. However, tissue respiratory function was not improved by Pio. Finally, TBI altered microvascular responses including promoting vascular accumulation of serum proteins and significantly impairing blood flow during the reperfusion period after stroke, both of which were reversed by treatment with Pio. Thus, TBI appears to exacerbate ischemic outcomes by impairing metabolic and microvascular physiology. These data have important implications because TBI patients experience strokes at greater rates than individuals without a history of head injury, but these data suggest that those strokes may also cause greater tissue damage and functional impairments in that population.

Crisis Management Simulation: Review of Current Experience.

Crisis management simulation is important in training the next generation of surgeons. In this review, we highlight our experiences with the cavernous carotid injury model. We then delve into other crisis simulation models available for the neurosurgical specialty. The discussion focuses upon how these trainings can continue to evolve. Much work is yet to be done in this exciting arena and we present several avenues for future discovery. Simulation continues to be an important training tool for the surgical learner.

Irradiator Commissioning and Dosimetry for Assessment of LQ α and ß Parameters, Radiation Dosing Schema, and in vivo Dose Deposition.

Radiation dosimetry is critical in the accurate delivery and reproducibility of radiation schemes in preclinical models for high translational relevance. Prior to performing any in vitro or in vivo experiments, the specific dose output for the irradiator and individual experimental designs must be assessed. Using an ionization chamber, electrometer, and solid water setup, the dose output of wide fields at isocenter can be determined. Using a similar setup with radiochromic films in the place of the ionization chamber, dose rates for smaller fields at different depths can also be determined. In vitro clonogenic survival assays of cancer cells in response to radiation treatment are inexpensive experiments that provide a measure of inherent radio-sensitivity of cell lines by fitting these data with the traditional linear-quadratic model. Model parameters estimated from these assays, combined with the principles of biologic effective doses, allows one to develop varying fractionation schedules for radiation treatment that provide equivalent effective doses in tumor-bearing animal experiments. This is an important factor to consider and correct for in comparing in vivo radiation therapy schedules to eliminate potential confounding of results due to variance in the delivered effective doses. Taken together, this article provides a general method for dose output verification preclinical animal and cabinet irradiators, in vitro assessment of radio-sensitivity, and verification of radiation delivery in small living organisms.

Disruption of metabolic, sleep, and sensorimotor functional outcomes in a female transgenic mouse model of Alzheimer's disease.

Alzheimer's Disease (AD) is the most prevalent form of dementia globally, and the number of individuals with AD diagnosis is expected to double by 2050. Numerous preclinical AD studies have shown that AD neuropathology accompanies alteration in learning and memory. However, less attention has been given to alterations in metabolism, sleep, and sensorimotor functional outcomes during AD pathogenesis. The objective of this study was to elucidate the extent to which metabolic activity, sleep-wake cycle, and sensorimotor function is impaired in APPSwDI/Nos2-/- (CVN-AD) transgenic mice. Female mice were used in this study because AD is more prevalent in women compared to men. We hypothesized that the presence of AD neuropathology in CVN-AD mice would accompany alterations in metabolic activity, sleep, and sensorimotor function. Our results showed that CVN-AD mice had significantly decreased energy expenditure compared to wild-type (WT) mice. An examination of associated functional outcome parameters showed that sleep activity was elevated during the awake (dark) cycle and as well as an overall decrease in spontaneous locomotor activity. An additional functional parameter, the nociceptive response to thermal stimuli, was also impaired in CVN-AD mice. Collectively, our results demonstrate CVN-AD mice exhibit alterations in functional parameters that resemble human-AD clinical progression.

Loss of tissue-nonspecific alkaline phosphatase (TNAP) enzyme activity in cerebral microvessels is coupled to persistent neuroinflammation and behavioral deficits in late sepsis.

Sepsis is a host response to systemic inflammation and infection that may lead to multi-organ dysfunction and eventual death. While acute brain dysfunction is common among all sepsis patients, chronic neurological impairment is prevalent among sepsis survivors. The brain microvasculature has emerged as a major determinant of sepsis-associated brain dysfunction, yet the mechanisms that underlie its associated neuroimmune perturbations and behavioral deficits are not well understood. An emerging body of data suggests that inhibition of tissue-nonspecific alkaline phosphatase (TNAP) enzyme activity in cerebral microvessels may be associated with changes in endothelial cell barrier integrity. The objective of this study was to elucidate the connection between alterations in cerebrovascular TNAP enzyme activity and brain microvascular dysfunction in late sepsis. We hypothesized that the disruption of TNAP enzymatic activity in cerebral microvessels would be coupled to the sustained loss of brain microvascular integrity, elevated neuroinflammatory responses, and behavioral deficits. Male mice were subjected to cecal ligation and puncture (CLP), a model of experimental sepsis, and assessed up to seven days post-sepsis. All mice were observed daily for sickness behavior and underwent behavioral testing. Our results showed a significant decrease in brain microvascular TNAP enzyme activity in the somatosensory cortex and spinal cord of septic mice but not in the CA1 and CA3 hippocampal regions. Furthermore, we showed that loss of cerebrovascular TNAP enzyme activity was coupled to a loss of claudin-5 and increased perivascular IgG infiltration in the somatosensory cortex. Analyses of whole brain myeloid and T-lymphoid cell populations also revealed a persistent elevation of infiltrating leukocytes, which included both neutrophil and monocyte myeloid derived suppressor cells (MDSCs). Regional analyses of the somatosensory cortex, hippocampus, and spinal cord revealed significant astrogliosis and microgliosis in the cortex and spinal cord of septic mice that was accompanied by significant microgliosis in the CA1 and CA3 hippocampal regions. Assessment of behavioral deficits revealed no changes in learning and memory or evoked locomotion. However, the hot plate test uncovered a novel anti-nociceptive phenotype in our septic mice, and we speculate that this phenotype may be a consequence of sustained GFAP astrogliosis and loss of TNAP activity in the somatosensory cortex and spinal cord of septic mice. Taken together, these results demonstrate that the loss of TNAP enzyme activity in cerebral microvessels during late sepsis is coupled to sustained neuroimmune dysfunction which may underlie, in part, the chronic neurological impairments observed in sepsis survivors.

Fornicotomy for the Treatment of Epilepsy: An Examination of Historical Literature in the Setting of Modern Operative Techniques.

Fornicotomy has been used to treat intractable temporal lobe epilepsy with mixed success historically; however, modern advances in stereotactic, neurosurgical, and imaging techniques offer new opportunities to target the fornix with greater precision and safety. In this review, we discuss the historical uses and quantify the outcomes of fornicotomy for the treatment of temporal lobe epilepsy, highlight the potential mechanisms of benefit, and address what is known about the side effects of the procedure. We find that fornicotomy, with or without anterior commissurotomy, resulted in 61% (83/136) of patients having some seizure control benefit. We discuss the potential operative approaches for targeting the fornix, including laser ablation and the use of focused ultrasound ablation. More work is needed to address the true efficacy of fornicotomy in the modern surgical setting. This review is intended to serve as a framework for developing this approach.

Systemic inhibition of tissue-nonspecific alkaline phosphatase alters the brain-immune axis in experimental sepsis.

Tissue-nonspecific alkaline phosphatase (TNAP) is a ubiquitous enzyme present in many cells and tissues, including the central nervous system. Yet its functions at the brain-immune axis remain unclear. The goal of this study was to use a novel small molecular inhibitor of TNAP, SBI-425, to interrogate the function of TNAP in neuroimmune disorders. Following intraperitoneal (IP) administration of SBI-425, mass spectrometry analysis revealed that the SBI-425 does not cross the blood-brain barrier (BBB) in healthy mice. To elucidate the role of TNAP at the brain-immune axis, mice were subjected to experimental sepsis and received either vehicle or SBI-425 (25 mg/kg, IP) daily for 7 days. While SBI-425 administration did not affect clinical severity outcomes, we found that SBI-425 administration suppressed CD4 + Foxp3+ CD25- and CD8 + Foxp3+ CD25- splenocyte T-cell populations compared to controls. Further evaluation of SBI-425's effects in the brain revealed that TNAP activity was suppressed in the brain parenchyma of SBI-425-treated mice compared to controls. When primary brain endothelial cells were treated with a proinflammatory stimulus the addition of SBI-425 treatment potentiated the loss of barrier function in BBB endothelial cells. To further demonstrate a protective role for TNAP at endothelial barriers within this axis, transgenic mice with a conditional overexpression of TNAP were subjected to experimental sepsis and found to have increased survival and decreased clinical severity scores compared to controls. Taken together, these results demonstrate a novel role for TNAP activity in shaping the dynamic interactions within the brain-immune axis.