Novel intravital approaches to quantify deep vascular structure and perfusion in the aging mouse brain using ultrasound localization microscopy (ULM).

Intra-vital visualization of deep cerebrovascular structures and blood flow in the aging brain has been a difficult challenge in the field of neurovascular research, especially when considering the key role played by the cerebrovasculature in the pathogenesis of both vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). Traditional imaging methods face difficulties with the thicker skull of older brains, making high-resolution imaging and cerebral blood flow (CBF) assessment challenging. However, functional ultrasound (fUS) imaging, an emerging non-invasive technique, provides real-time CBF insights with notable spatial-temporal resolution. This study introduces an enhanced longitudinal fUS method for aging brains. Using elderly (24-month C57BL/6) mice, we detail replacing the skull with a polymethylpentene window for consistent fUS imaging over extended periods. Ultrasound localization mapping (ULM), involving the injection of a microbubble (<<10 µm) suspension allows for recording of high-resolution microvascular vessels and flows. ULM relies on the localization and tracking of single circulating microbubbles in the blood flow. A FIJI-based analysis interprets these high-quality ULM visuals. Testing on older mouse brains, our method successfully unveils intricate vascular specifics even in-depth, showcasing its utility for longitudinal studies that require ongoing evaluations of CBF and vascular aspects in aging-focused research.

Time-restricted feeding improves aortic endothelial relaxation by enhancing mitochondrial function and attenuating oxidative stress in aged mice.

Age-related endothelial dysfunction is a pivotal factor in the development of cardiovascular diseases, stemming, at least in part, from mitochondrial dysfunction and a consequential increase in oxidative stress. These alterations are central to the decline in vascular health seen with aging, underscoring the urgent need for interventions capable of restoring endothelial function for preventing cardiovascular diseases. Dietary interventions, notably time-restricted feeding (TRF), have been identified for their anti-aging effects on mitochondria, offering protection against age-associated declines in skeletal muscle and other organs. Motivated by these findings, our study aimed to investigate whether TRF could similarly exert protective effects on endothelial health in the vasculature, enhancing mitochondrial function and reducing oxidative stress. To explore this, 12-month-old C57BL/6 mice were placed on a TRF diet, with food access limited to a 6-h window daily for 12 months. For comparison, we included groups of young mice and age-matched controls with unrestricted feeding. We evaluated the impact of TRF on endothelial function by measuring acetylcholine-induced vasorelaxation of the aorta. Mitochondrial health was assessed using fluororespirometry, and vascular reactive oxygen species (ROS) production was quantified with the redox-sensitive dye dihydroethidium. We also quantified 4-hydroxynonenal (4-HNE) levels, a stable marker of lipid peroxidation, in the aorta using ELISA. Our findings demonstrated that aged mice on a standard diet exhibited significant impairments in aortic endothelial relaxation and mitochondrial function, associated with elevated vascular oxidative stress. Remarkably, the TRF regimen led to substantial improvements in these parameters, indicating enhanced endothelial vasorelaxation, better mitochondrial function, and reduced oxidative stress in the aortas of aged mice. This investigation establishes a vital foundation, paving the way for subsequent clinical research aimed at exploring the cardiovascular protective benefits of intermittent fasting.

Acute Macrocystic Thoracic Schwannoma: Systematic Review and Illustrative Case Example.

BACKGROUND: Schwannomas are benign peripheral nerve sheath tumors arising from myelinating Schwann cells. Although macrocystic changes are regularly encountered in schwannoma variants such as vestibular nerve tumors, they are exceedingly rare among spinal neoplasms. METHODS: Case report and systematic review of 4 databases (Ovid Medline, PubMed, Science Direct, and SCOPUS) from inception to present. All peer-reviewed publications reporting intradural cystic thoracic schwannoma were included. RESULTS: We identified 8 publications documenting 9 cases of cystic thoracic schwannoma. Four were female, 5 male; median age was 41 years (range, 27-80). Presentations ranged from incidental to pain, sensory changes, lower extremity paresis, or bowel/bladder dysfunction. Characteristic radiographic findings included T1 hypointensity, T2 hyperintensity, and cord effacement or compression. The present case followed a similar pattern: a 52-year-old male presented with worsening bilateral lower extremity weakness, low back pain, and gait dysfunction, worsening over 3 days. Examination also revealed decreased left lower extremity sensation. Imaging identified a well-delineated intradural, extramedullary macrocystic extending over T7-T10. The patient underwent a laminectomy resulting in complete tumor resection and restoration of intact neurologic function. Final pathology confirmed benign cystic schwannoma. CONCLUSIONS: Macrocystic thoracic schwannomas are exceedingly rare and lack a comprehensive scheme for clinical classification of their natural history and pathogenesis. We report the 10th case of such a schwannoma, and the first associated systematic review. Although macrocystic thoracic schwannomas are not frequently encountered, accurate diagnosis and appropriate neurosurgical treatment is critical in these vulnerable patients, given the opportunity for excellent functional outcomes following neurosurgical treatment.

Preventing Sudden Cessation of Implantable Pulse Generators in Deep Brain Stimulation: A Systematic Review and Protocol Proposal.

INTRODUCTION: Deep brain stimulation (DBS) requires a consistent electrical supply from the implantable pulse generator (IPG). Patients may struggle to monitor their IPG, risking severe complications in battery failure. This review assesses current literature on DBS IPG battery life management and proposes a protocol for healthcare providers. METHODS: A literature search using four databases identified best practices for DBS IPG management. Studies were appraised for IPG management guidelines, categorized as qualitative, quantitative, or both. RESULTS: Of 408 citations, only seven studies were eligible, none providing clear patient management strategies. Current guidelines lack specificity, relying on clinician suggestions. CONCLUSION: Limited guidelines exist for IPG management. Specificity and adaptability to emerging technology are crucial. The findings highlight the need for specificity in patients' needs and adaptability to emerging technology in future studies. To address this need, we developed a protocol for DBS IPG management that we have implemented at our own institution. Further research is needed for effective DBS IPG battery life management, preventing therapy cessation complications.

Learning Curve in Robotic Stereoelectroencephalography: Single Platform Experience.

BACKGROUND: Learning curve, training, and cost impede widespread implementation of new technology. Neurosurgical robotic technology introduces challenges to visuospatial reasoning and requires the acquisition of new fine motor skills. Studies detailing operative workflow, learning curve, and patient outcomes are needed to describe the utility and cost-effectiveness of new robotic technology. METHODS: A retrospective analysis was performed of pediatric patients who underwent robotic stereoelectroencephalography (sEEG) with the Medtronic Stealth Autoguide. Workflow, total operative time, and time per electrode were evaluated alongside target accuracy assessed via error measurements and root sum square. Patient demographics and clinical outcomes related to sEEG were also assessed. RESULTS: Robot-assisted sEEG was performed in 12 pediatric patients. Comparison of cases over time demonstrated a mean operative time of 363.3 ± 109.5 minutes for the first 6 cases and 256.3 ± 59.1 minutes for the second 6 cases, with reduced operative time per electrode (P = 0.037). Mean entry point error, target point error, and depth point error were 1.82 ± 0.77 mm, 2.26 ± 0.71 mm, and 1.27 ± 0.53 mm, respectively, with mean root sum square of 3.23 ± 0.97 mm. Error measurements between magnetic resonance imaging and computed tomography angiography found computed tomography angiography to be more accurate with significant differences in mean entry point error (P = 0.043) and mean target point error (P = 0.035). The epileptogenic zone was identified in 11 patients, with therapeutic surgeries following in 9 patients, of whom 78% achieved an Engel class I. CONCLUSIONS: This study demonstrated institutional workflow evolution and learning curve for the Autoguide in pediatric sEEG, resulting in reduced operative times and increased accuracy over a small number of cases. The platform may seamlessly and quickly be incorporated into clinical practice, and the provided workflow can facilitate a smooth transition.

Hyperbaric oxygen alleviates selective domains of cognitive and motor deficits in female 5xFAD mice.

Treatment of Alzheimer's disease (AD) has been limited to managing of symptoms or anti-amyloid therapy with limited results and uncertainty. Seeking out new therapies that can reverse the effects of this devastating disease is important. Hyperbaric oxygen (HBO) therapy could be such a candidate as it has been shown to improve brain function in certain neurological conditions. Furthermore, the role sex plays in the vulnerability/resilience to AD remains equivocal. An understanding of what makes one sex more vulnerable to AD could unveil new pathways for therapy development. In this study, we investigated the effects of HBO on cognitive, motor, and affective function in a mouse model of AD (5xFAD) and assessed protein oxidation in peripheral tissues as a safety indicator. The motor and cognitive abilities of 5xFAD mice were significantly impaired. HBO therapy improved cognitive flexibility and associative learning of 5xFAD females but not males, but HBO had no effect other aspects of cognition. HBO also reversed AD-related declines in balance but had no impact on gait and anxiety-like behavior. HBO did not affect body weights or oxidative stress in peripheral tissues. Our study provides further support for HBO therapy as a potential treatment for AD and emphasizes the importance of considering sex as a biological variable in therapeutic development. Further investigations into the underlying mechanisms of HBO's sex-specific responses are warranted, as well as optimizing treatment protocols for maximum benefits.

Decision-Making in Clival Mass Lesions: Risk Factors for Malignant Disease and an Illustrative Case Example.

Introduction Clival tumors are rare and heterogeneous. Although some benign prototypical sellar lesions may present as clival tumors, the likelihood of malignant disease is higher. Here we define a novel algorithm for the workup and management of clival masses through an illustrative case of colorectal adenocarcinoma metastasis to the clivus. Methods In this case report, the best practice guidelines for managing clival masses are described through a literature review and refined by senior author consensus. We conducted a focused systematic review to characterize the present case in the context of clival metastasis from gastrointestinal malignancy. Results An 83-year-old woman presented with 4 weeks of headaches and blurry vision. Examination revealed partial right abducens and left oculomotor palsies. Magnetic resonance imaging (MRI) identified a large, weakly enhancing sellar and clival mass with sphenoid sinus extension. An aggressive subtotal endoscopic endonasal resection was performed with removal of all sphenoid, clival, and sellar disease without cavernous sinus wall resection. Pathology confirmed colorectal adenocarcinoma; computed tomography (CT) imaging identified an ascending colon mass with metastases to the liver and mesenteric nodes. Palliative oncologic therapies were recommended, but she elected hospice, and died 3 months after initial presentation. Gastrointestinal clival metastases are exceedingly rare among sellar and clival pathologies, with eight prior cases reported, most of which presented with diplopia from abducens nerve involvement. Conclusion Clival masses are uncommon skull base lesions that are associated with more aggressive diseases. We present a consolidated framework for decision-making in these challenging patients, alongside an unusual case example that illustrates the importance of increased suspicion for malignant clinical entities in this setting.

Gender diversity in neurosurgical training: an analysis of trends and resident program characteristics.

OBJECTIVE: Recent trends have shown more women entering neurosurgery, but large gender gaps in the number of female trainees continue to persist. A previous study on the gender diversity of residents and faculty in neurosurgery training programs found that only 18.2% of residents and 8.7% of faculty at neurosurgical training programs were female. The goal of this study was to better understand program characteristics that may affect the recruitment of female residents and the gender composition of neurosurgery residency programs. METHODS: The authors assessed publicly available information on websites and social media from 116 Accreditation Council for Graduate Medical Education (ACGME)-accredited neurosurgery residency programs from the 2022-2023 academic year. Data collected on residents included gender and postgraduate year (PGY), geographic region, accreditation year, and complement size for programs. The authors analyzed the distribution of female residents at each program and compared accreditation year, program size, program geographics, PGY, and acceptance rates. RESULTS: There were 1602 residents across the 116 programs included in this study: 1223 (76.3%) male and 379 (23.7%) female residents. The gender distribution of female residents showed 29 programs had 30% or more female residents, 50 programs had between 16% and 30%, and 37 had fewer than 16%, including 8 with none. There were significantly more PGY-1 than PGY-7 female residents (28.9% vs 16.4%, p < 0.01). Programs with ACGME accreditation before 1970 had significantly higher percentages of female residents (26.0%) compared with those accredited after 1970 (18.2%, p < 0.01). Program size was associated with a higher percentage of female residents (large = 25.2%, medium = 24.9%, and small = 19.6%), although the results were not significant. The distribution of female trainees across five geographic regions of the United States was fairly even: Northeast (24.5%), West (25.2%), South Atlantic (23.1%), South Central (21.8%), and North Central (21.2%). Residency acceptance rates were similar between genders. CONCLUSIONS: The underrepresentation of women in neurosurgery residency programs remains a significant issue. While some programs have achieved higher female representation than the overall average proportion of female neurosurgery residents, many still fall short. There are twice as many female PGY-1 compared with PGY-7 residents, suggesting increased recruitment over the past few years. Programs with longer accreditation histories have significantly higher proportions of female residents. Larger program size can also play a role in attracting more female residents, but geographic location did not impact gender composition of resident cohorts in this study.

Deep brain stimulation in a pediatric dystonia patient with cochlear implants and mitochondrial disorder: novel application of a frameless stereotactic system and navigating the anesthesia choice and neurosurgical complexities. Illustrative case.

BACKGROUND: This report presents a case of medically refractory dystonia in a pediatric patient successfully treated with bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) while under general anesthesia by using microelectrode recordings (MERs) with intraoperative computed tomography (CT). OBSERVATIONS: The patient was an 18-year-old female with primary dystonia secondary to mitochondrial Leigh syndrome. Her past medical history was significant for complex partial epilepsy and hearing loss treated with cochlear implants. Her cochlear implants precluded anatomical targeting via magnetic resonance imaging. Additionally, the patient could not tolerate awake surgery with MER. The decision was made to proceed with bilateral STN DBS with intraoperative CT with the patient under general anesthesia. The patient's cochlear implants made standard frame placement difficult, so navigation was performed with the Nexframe system. Recordings were obtained with the patient under general anesthesia with ketamine, dexmedetomidine, and remifentanil. At the 3- and 6-month follow-ups, the patient demonstrated marked improvement in dystonia without neurological complications. LESSONS: This is the first case of dystonia secondary to Leigh syndrome treated with DBS. Additionally, the authors describe the novel use of the Nexframe for DBS lead placement in a pediatric patient. This demonstrates that STN DBS with the use of MER and intraoperative CT can be a safe and effective method of treating dystonia in certain pediatric patients.

Chronic cerebrospinal fluid rhinorrhea as an initial presentation of chordoma: illustrative case.

BACKGROUND: Skull base chordomas are typically extradural and present with cranial nerve deficits, headache, and visual disturbances. Clival chordoma involving the dura and presenting as a spontaneous cerebrospinal fluid (CSF) leak is extremely rare and can be mistaken for other skull base lesions. Here the authors present a case of chordoma with an unusual presentation. OBSERVATIONS: A 43-year-old female who presented with clear nasal drainage was diagnosed with CSF rhinorrhea secondary to a clival defect previously thought to be ecchordosis physaliphora. The patient subsequently developed bacterial meningitis and underwent endoscopic, endonasal, transclival gross-total resection of the lesion with repair of the dural defect. Pathology revealed brachyury-positive chordoma. She received adjuvant proton beam radiotherapy and has remained stable for 2 years. LESSONS: Spontaneous CSF rhinorrhea can occur as a rare primary presentation of clival chordoma, requiring careful radiological interpretation and a high index of suspicion for diagnosis. Chordoma cannot be reliably differentiated from benign notochordal lesions based on imaging alone; thus, intraoperative exploration and immunohistochemistry play key roles. Clival lesions presenting with CSF rhinorrhea should undergo prompt resection to facilitate diagnosis and prevent complications. Future studies on connections between chordoma and benign notochordal lesions may help to establish management guidelines.

The role of endothelial TRP channels in age-related vascular cognitive impairment and dementia.

Transient receptor potential (TRP) proteins are part of a superfamily of polymodal cation channels that can be activated by mechanical, physical, and chemical stimuli. In the vascular endothelium, TRP channels regulate two fundamental parameters: the membrane potential and the intracellular Ca2+ concentration [(Ca2+)i]. TRP channels are widely expressed in the cerebrovascular endothelium, and are emerging as important mediators of several brain microvascular functions (e.g., neurovascular coupling, endothelial function, and blood-brain barrier permeability), which become impaired with aging. Aging is the most significant risk factor for vascular cognitive impairment (VCI), and the number of individuals affected by VCI is expected to exponentially increase in the coming decades. Yet, there are currently no preventative or therapeutic treatments available against the development and progression of VCI. In this review, we discuss the involvement of endothelial TRP channels in diverse physiological processes in the brain as well as in the pathogenesis of age-related VCI to explore future potential neuroprotective strategies.

Review of Pediatric Extraosseous Chordomas with a Unique, Illustrative Case.

INTRODUCTION: Chordoma is a rare, aggressive tumor that is believed to originate from notochord remnants. It can occur anywhere from the clivus to the sacrum and often recurs even after resection and radiotherapy. We present a unique case that initially suggested a different pathology based on imaging and presentation but was found to be a chordoma on gross and pathological analysis. CASE PRESENTATION: An 11-year-old girl presented outpatient for scoliosis evaluation and was found to have what appeared to be a right L4 peripheral nerve sheath tumor on MRI, causing dextroconvex scoliosis. She underwent a gross total resection via a retroperitoneal approach and was found to have what appeared to be an extraosseous, extradural, extra-spinal canal lumbar chordoma. Immunohistochemical features on surgical pathology were consistent with chordoma. The patient was referred to radiation oncology for adjuvant radiotherapy and pediatric hematology/oncology for recurrence monitoring. DISCUSSION: Our case is the first to present in such a manner, was shown to be external to the spinal canal, encasing the nerve root, and was the first such case in a pediatric patient. We reviewed the growing body of literature on spinal extraosseous chordomas and their characteristics within the pediatric patient population. We also reviewed chordoma pathogenesis theories as well as current and future treatment options.

Influence of the living Pareto chart and data transparency on patient outcomes in neurosurgery.

OBJECTIVE: Quality improvement (QI) tools are increasingly being used to calibrate healthcare quality. Achieving healthcare quality is essential, as there is a movement toward value-based healthcare delivery. Visual management, such as a living Pareto chart, is a strategy for improvement within the QI framework. The authors herein hypothesized that transparency of data through a living Pareto chart is a powerful way to improve patient outcomes and gain clinical efficiency. METHODS: The authors retrospectively reviewed patient outcomes and complications; cerebrospinal fluid (CSF) leaks; shunt, baclofen, and other surgical site infections; readmission rates; and same- or next-day appointments in a cohort of patients at the Riley Hospital for Children from November 1, 2016, to May 31, 2020. Similarly, they reviewed neurosurgical outcomes and complications at a second institution, the Oklahoma Children's Hospital, where a living Pareto chart was utilized from February 1, 2021, to March 31, 2022. The discrete frequency and rates per month of outcomes and complications were graphed on scatterplots, Pearson correlation coefficients were calculated to measure the strength of the relationship between event frequency and time, and best-fit lines illustrated the relationship between those points through the least-squares method. RESULTS: At both the Riley Hospital for Children and Oklahoma Children's Hospital, the use of a living Pareto chart to display data transparently was associated with decreasing infections, and it was associated with decreasing readmissions at Riley. On the other hand, it encouraged same- or next-day clinic appointments to be offered to patients and families. Interestingly, CSF leaks were not mitigated with data transparency alone. CONCLUSIONS: Transparency is a driver of change in patient, provider, and institutional behaviors. It is an essential element of QI and patient safety, as well as building a culture of trust. Readmissions, infections, and same- or next-day appointments were influenced by the living Pareto chart; however, CSF leaks remained recalcitrant to data transparency. Other QI strategies may be necessary to positively affect the occurrence of CSF leaks in neurosurgery.

Platelet-Rich Plasma Injections: Pharmacological and Clinical Considerations in Pain Management.

PURPOSE OF REVIEW: Regenerative medicine through interventional pain procedures is evolving with data demonstrating efficacy for a number of pain states in recent years. Platelet-rich plasma (PRP), defined as a sample of plasma with a platelet concentration 3 to 5 times greater than the physiologic platelet concentration found in healthy whole blood, releases bioactive proteins which can restore anatomical function in degenerative states. PRP is dense in growth factors, such as platelet-derived growth factor, transforming growth factor-beta1, basic fibroblastic growth factor, vascular endothelial growth factor, and epidermal growth factors. RECENT FINDINGS: To date, well-designed case-control or cohort studies for the use of PRP have demonstrated efficacy in lumbar facet joint, lumbar epidural, and sacroiliac joint injections. At present, there is only level IV evidence indicating the need for larger and more carefully controlled prospective studies. PRP is utilized autogenously in order to facilitate healing and injection and has been studied in the long-term management of discogenic low back pain. In this regard, numerous studies have evaluated PRP to steroid injections in chronic pain states with favorable results. PRP represents an opportunity for a new strategy in the therapeutic treatment of degenerative states of spines, joints, and other locations throughout the body with evolving data demonstrating both safety and long-term efficacy.

Impact of Obesity and Diabetes on Postoperative Outcomes Following Surgical Treatment of Nontraumatic Subarachnoid Hemorrhage: Analysis of the ACS-NSQIP Database.

BACKGROUND: Nontraumatic subarachnoid hemorrhage (SAH) refers to high pressure extravasation of blood into the subarachnoid space that typically occurs spontaneously from rupture of cerebral aneurysm. The purpose of this study was to identify postoperative complications requiring increased surveillance in obese, diabetic, and hypertensive patients. METHODS: Patients who underwent surgical treatment for nontraumatic SAH were queried in the American College of Surgeons National Surgical Quality Improvement Program database from the years 2012-2018. Cases were identified using International Classification of Diseases codes and then classified independently by 3 dichotomous diagnoses: obesity, diabetes, and hypertension. RESULTS: Among 1002 patients meeting inclusion criteria, 311 (31%) were obese (body mass index >30), 86 (9%) had diabetes treated with insulin or noninsulin agents, and 409 (41%) required medication for hypertension. There was a statistically significant association between diabetes and postoperative pneumonia (odds ratio [OR] = 1.694; 95% confidence interval [CI] = 0.995-2.883; P = 0.050), prolonged ventilator dependence (OR = 1.700; 95% CI = 1.087-2.661; P = 0.019), and death (OR = 1.846; 95% CI = 1.071-3.179; P = 0.025). Medication-dependent hypertension was statistically associated with incidence of stroke/cerebrovascular accident (OR = 1.763; 95% CI = 1.056-2.943; P = 0.023). Obesity was not associated with adverse outcomes in this population. CONCLUSIONS: In patients undergoing surgical management of SAH, hypertensive and diabetic patients had poorer outcomes, including prolonged ventilator dependence, pneumonia, stroke/cerebrovascular accident, and death. Surprisingly, preexisting obesity was not associated with poor outcomes. In fact, overweight body mass index, class I obesity, and class II obesity had decreased need for transfusion in the 30-day postoperative period.

Women in Neurosurgery Around the World: A Systematic Review and Discussion of Barriers, Training, Professional Development, and Solutions.

BACKGROUND: Women have been a minority in neurosurgery since the foundation of the specialty. Women who choose to pursue neurosurgery or advance in their career must overcome various obstacles. In this article, we discuss the proportion of women in neurosurgery globally and the obstacles they face, as well as the solutions being implemented. METHODS: A systematic review of studies concerning international women in neurosurgery was conducted. Article inclusion was assessed based on relevance to women of neurosurgery, geographic region, date, and classification (rates/data, barriers, or solutions). RESULTS: From the specified search, 127 articles were retrieved, and 27 met the inclusion criteria. Of the total, 25 countries were represented and discussed in the articles. Primary classification of articles resulted in 50 for data/rates, 22 for barriers, and 17 for possible solutions. DISCUSSION: Despite cultural differences among unique regions of the globe, women face similar challenges when pursuing neurosurgery, such as difficulty advancing their careers, balancing duties at work and at home, meeting social and cultural expectations, and finding support and mentorship. Encouragingly, measures are already being implemented worldwide to allow women to fulfill their multiple other roles through maternity leave policies, increasing their access to mentors, and enabling promotions throughout their careers. CONCLUSIONS: With the shortage of neurosurgeons in many regions of the world, the recruitment of female neurosurgeons plays a vital role in meeting those demands. Our cultures and professional societies should celebrate their inclusion and promotion and accommodate the complex role of women as neurosurgeons, mothers, partners, scientists, and leaders.

Robotics in spine surgery: A systematic review.

Robotic systems to assist with pedicle screw placement have recently emerged in the field of spine surgery. Here, the authors systematically reviewed the literature for evidence of these robotic systems and their utility. Thirty-four studies that reported the use of spinal instrumentation with robotic assistance and met inclusion criteria were identified. The outcome measures gathered included: pedicle screw accuracy, indications for surgery, rates of conversion to an alternative surgical method, radiation exposure, and learning curve. In our search there were five different robotic systems identified. All studies reported accuracy and the most commonly used accuracy grading scale was the Gertzbein Robbins scale (GRS). Accuracy of clinically acceptable pedicle screws, defined as < 2 mm cortical breech, ranged from 80% to 100%. Many studies categorized indications for robotic surgery with the most common being degenerative entities. Some studies reported rates of conversion from robotic assistance to manual instrumentation due to many reasons, with robotic failure as the most common. Radiation exposure data revealed a majority of studies reported less radiation using robotic systems. Studies looking at a learning curve effect with surgeon use of robotic assistance were not consistent across the literature. Robotic systems for assistance in spine surgery have continued to improve and the accuracy of pedicle screw placement remains superior when compared to free-hand technique, however rates of manual conversion are significant. Currently, these systems are successfully employed in various pathological entities where trained spine surgeons can be safe and accurate regardless of robotic training.

Investigation of Solid Dosage Form Components Interaction Using Orthogonal Techniques- Discovery of New Forms of Sodium Stearyl Fumarate.

Physical or chemical interactions between drug product (DP) components can occur during manufacturing and/or upon storage; and may alter DP shelf life and performance. In this work a new Powder X-ray Diffraction (PXRD) peak was observed in DP under accelerated storage conditions. Due to the complex drug product matrix (including API, polymer, fillers, super disintegrant and lubricant), it was challenging to pinpoint the component(s) responsible for the new peak. In addition to PXRD, other orthogonal techniques including Differential Scanning Calorimetry (DSC), thermogravimetric analysis (TGA), dynamic vapor sorption (DVS), Solid State Nuclear Magnetic Resonance (SSNMR) and Infrared (IR) spectroscopy were employed in this investigation to understand the root cause mechanistically. Specifically, multi nuclei SSNMR (1H, 23Na, 13C) was instrumental in delineating the components of the matrix. We identified the root cause to be an acid base reaction occurring in the DP, whereby sodium ion in sodium stearyl fumarate (SSF) is replaced by proton leading to SSF form conversion. We also identified commercially available SSF to be a hydrate that can dehydrate to an anhydrous form upon heating. In general, the same techniques can be used to investigate interactions of any multi component solid dosage forms.

Rosette-forming glioneuronal tumor: an illustrative case and a systematic review.

BACKGROUND: Rosette-forming glioneuronal tumors (RGNTs) are rare, low-grade, primary CNS tumors first described in 2002 by Komori et al. RGNTs were initially characterized as a World Health Organization (WHO) grade I tumors typically localized to the fourth ventricle. Although commonly associated with an indolent course, RGNTs have the potential for aggressive behavior. METHODS: A comprehensive search of PubMed and Web of Science was performed through November 2019 using the search term "rosette-forming glioneuronal tumor." Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. English, full-text case reports and series with histopathological confirmation were included. Patient demographics, presentations, MRI features, tumor location, treatment, and follow-up of all 130 cases were extracted. RESULTS: A 19-year-old man with a history of epilepsy and autism presented with acute hydrocephalus. MRI scans from 2013 to 2016 demonstrated unchanged abnormal areas of cortex in the left temporal lobe with extension into the deep gray-white matter. On presentation to our clinic in 2019, the lesion demonstrated significant progression. The patient's tumor was identified as RGNT, WHO grade I. One hundred thirty patients were identified across 80 studies. CONCLUSION: RGNT has potential to transform from an indolent tumor to a tumor with more aggressive behavior. The results of our systematic review provide insight into the natural history and treatment outcomes of these rare tumors.