Decrease in the Ratio proBDNF/BDNF in the Urine of Aging Female Patients with OAB.

Imbalance in the levels of neurotrophins, growth factors crucial in the development, function, and survival of neurons is commonly observed in many pathological states. Concentrations of brain-derived neurotrophic factor (BDNF) and its precursor (proBDNF) were measured in the urine of a cohort of aging female patients with overactive bladder disease (OAB). When reported to creatinine, levels were similar between OAB patients and healthy controls. However, the ratio proBDNF/BDNF was significantly decreased in the OAB group. Receiver operating characteristic (ROC) curve analysis of the ratio proBDNF/BDNF displayed a good diagnostic value for OAB (AUC = 0.729). Clinical questionnaires of symptom severity (OABSS and IIQ-7) were negatively correlated with this ratio. On the other hand, microRNAs (miRNA) involved in proBDNF gene translation were expressed at comparable levels between groups. However, urinary enzymatic activity of matrix metalloproteinase-9 (MMP-9), the enzyme that cleaves proBDNF into BDNF, was increased in OAB compared to controls. Levels of miR-491-5p, the main miRNA that downregulates MMP-9 synthesis, were greatly decreased in urine from OAB patients. These results suggest that the ratio proBDNF/BDNF could be useful in the phenotyping of OAB in an aging population, and the difference could originate from enhanced MMP-9 enzymatic activity rather than translational control.

Bellevue Hospital, the Oldest Public Health Center in the United States of America.

Bellevue Hospital is known as the oldest public hospital in the United States of America. Although its historical beginnings date back to the 1600s, it was officially founded on the second floor of the New York City Almshouse in 1736, 40 years before the American Revolution. It has since been at the forefront of administering comprehensive patient care and medical education. Moreover, Bellevue has built a reputation for serving homeless, immigrant, or minority populations while also delivering care to United States presidents. This tradition of treating patients regardless of socioeconomic or racial status has made Bellevue one of the most historically renowned hospitals in the country. Today, Bellevue hospital represents a significant branch of the New York City health system and a public health leader. Moreover, it has housed pioneers in neurosurgery, including the father of functional ultrasonic neurosurgery, Dr. Russel Meyers, as well as Dr. Dorothy Klenke Nash, the only active female neurosurgeon in the United States from 1928 to 1960. Herein, we will explore Bellevue's historical and medical significance, from its humble beginnings to its current status as a public health leader.

Staying Cool in Space: A Review of Therapeutic Hypothermia and Potential Application for Space Medicine.

Despite rigorous health screenings, medical incidents during spaceflight missions cannot be avoided. With long-duration exploration flights on the rise, the likelihood of critical medical conditions with no suitable treatment on board will increase. Therapeutic hypothermia (TH) could serve as a bridge treatment in space prolonging survival and reducing neurological damage in ischemic conditions such as stroke and cardiac arrest. We conducted a review of published studies to determine the potential and challenges of TH in space based on its physiological effects, the cooling methods available, and clinical evidence on Earth. Currently, investigators have found that application of low normothermia leads to better outcomes than mild hypothermia. Data on the impact of hypothermia on a favorable neurological outcome are inconclusive due to lack of standardized protocols across hospitals and the heterogeneity of medical conditions. Adverse effects with systemic cooling are widely reported, and could be reduced through selective brain cooling and pharmacological cooling, promising techniques that currently lack clinical evidence. We hypothesize that TH has the potential for application as supportive treatment for multiple medical conditions in space and recommend further investigation of the concept in feasibility studies.

Current uses, emerging applications, and clinical integration of artificial intelligence in neuroradiology.

Artificial intelligence (AI) is a branch of computer science with a variety of subfields and techniques, exploited to serve as a deductive tool that performs tasks originally requiring human cognition. AI tools and its subdomains are being incorporated into healthcare delivery for the improvement of medical data interpretation encompassing clinical management, diagnostics, and prognostic outcomes. In the field of neuroradiology, AI manifested through deep machine learning and connected neural networks (CNNs) has demonstrated incredible accuracy in identifying pathology and aiding in diagnosis and prognostication in several areas of neurology and neurosurgery. In this literature review, we survey the available clinical data highlighting the utilization of AI in the field of neuroradiology across multiple neurological and neurosurgical subspecialties. In addition, we discuss the emerging role of AI in neuroradiology, its strengths and limitations, as well as future needs in strengthening its role in clinical practice. Our review evaluated data across several subspecialties of neurology and neurosurgery including vascular neurology, spinal pathology, traumatic brain injury (TBI), neuro-oncology, multiple sclerosis, Alzheimer's disease, and epilepsy. AI has established a strong presence within the realm of neuroradiology as a successful and largely supportive technology aiding in the interpretation, diagnosis, and even prognostication of various pathologies. More research is warranted to establish its full scientific validity and determine its maximum potential to aid in optimizing and providing the most accurate imaging interpretation.

Sternotomy Approach to the Anterior Cervicothoracic Spine.

The anterior cervicothoracic spine is a challenging region to approach given the various vascular, osseous, nervous, and articular structures, which prevent adequate exposure. This region is susceptible to lesions ranging from tumors, degenerative disease, infectious processes, and traumatic fractures. Our objective was to critically evaluate the sternotomy approach in spine surgery to give the technical implications of its usage. The safety and efficacy of the transsternal approach are discussed as well as the advantages, disadvantages, indications, and contraindications. The transsternal approach is the most direct access to pathologies in the upper anterior cervicothoracic spine and enables the spine surgeon to gain direct exposure to the cervicothoracic junction for ideal visualization. Anatomical considerations must be kept in mind while performing a sternotomy to prevent complications such as denervation or bleeding. This technique is useful for the armamentarium of spinal surgeons.

Sacroiliac Joint and Pelvic Dysfunction Due to Symphysiolysis in Postpartum Women.

Pregnancy-related pain in the sacroiliac joint (SIJ), lumbosacral region, pubic symphysis, or in any combination of these joints has been coined as pelvic girdle pain (PGP) and has been estimated to affect almost half of all pregnant women. SIJ dysfunction in pregnancy is due to multiple biomechanical mechanisms, such as increased weight, change in posture, increased abdominal and intrauterine pressure, and laxity of the spine and pelvic structures. Moreover, when compared to men, women have increased SIJ mobility due to increased pubic angle and decreased SIJ curvature. These differences may assist in parturition where hormones, such as relaxin and estrogen, cause symphysiolysis. A retrospective review of the literature was conducted in the PubMed database using the search term "pregnancy-related sacroiliac joint pain." All peer-reviewed studies were included. Around 8%-10% of women with PGP continue to have pain for one to two years postpartum. Patients that were treated with SIJ fusion show statistically significant improvement in pain scores when compared to patients that had non-operative treatment. Although we have a number of studies following patients after sacroiliac (SI) joint fusion for pelvic pain with SI joint dysfunction, further research is needed to study sacroiliac fusion for SI joint dysfunction in postpartum women to better tailor and optimize surgical outcomes for this patient population.

Neuroprotective strategies of cerebrolysin for the treatment of infants with neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Perinatal asphyxia (PA) is a devastating neonatal condition characterized by a lack of oxygen supporting the organ systems. PA can lead to hypoxic-ischemic encephalopathy (HIE), a brain dysfunction due to oxygen deprivation with a complex neurological sequela. The pathophysiology of HIE and PA is not entirely understood, with therapeutic hypothermia being the standard treatment with only limited value. However, alternative neuroprotective therapies can be a potential treatment modality. METHODS: In this review, we will characterize the biochemical mechanisms of PA and HIE, while also giving insight into cerebrolysin, a neuroprotective treatment used for HIE and PA. RESULTS: We found that cerebrolysin has up to 6-month treatment window post-ischemic insult. Cerebrolysin injections of 0.1 ml/kg of body weight twice per week were found to provide gross motor and speech deficit improvement. CONCLUSION: Our literature search emphasizes the positive effects of cerebrolysin for general improvement outcomes. Nevertheless, biomarker establishment is warranted to improve patient outcomes.

Neuroimmunology and Novel Methods of Treatment for Acute Transverse Myelitis.

Acute transverse myelitis (ATM) is a rare, immune-mediated pathology that is defined as an adverse inflammatory response in the spinal cord leading to neurologic injury. The pathophysiology of ATM is poorly understood, with no apparent differences in age, ethnicities, or race, along with variable radiographic and clinical presentation. Therefore, in this review, we will characterize what is known about ATM's etiology and diagnostic criteria, and relate it to properties of neuroimmunology. Moreover, we will further discuss current treatment options, along with potential novel methods, to provide a comprehensive overview of the status of ATM's research development. Among these novel treatments, potassium blockers reveal exciting early outcomes in restoring neurologic motor function. In addition, human glial progenitor cell transportations have been described as a potential treatment through integrating and remyelinating lesion sites. Nevertheless, despite these novel methods, there is a paucity of clinical trials establishing ATM's immunopathology and the therapeutic role of potential treatment methods. Therefore, we will highlight the importance of larger well-designed clinical trials in revealing significant biomarkers of injury and recovery.

Bench to Bedside: Proteomic Biomarker Analysis of Cerebrospinal Fluid in Patients With Spondylomyelopathy.

Establishing proteomic biomarkers is critical for characterizing disease pathophysiology, identifying genetic risk factors, and predicting clinical outcomes. However, diseases like cervical spondylomyelopathy have not been actively characterized for molecular significance, leading to questions regarding the pathology's molecular mechanisms. Namely, spondylomyelopathy is a degenerative spinal disease that leads to compression and neurologic deficits in the spinal cord. Analyzing a patient's cerebrospinal fluid (CSF) has been well-known for revealing biomarkers that are associated with diseases of the central nervous system. Therefore, in this review, we will formulate a proteomic profile of spondylomyelopathy through a molecular analysis of the CSF. The proteins found to be upregulated in the CSF include vitamin D-binding protein (VDBP), gelsolin, creatine kinase B-type (CK-BB), and angiotensinogen. Meanwhile, the proteins that were downregulated include pigment epithelium-derived factor (PEDF), prostaglandin-H2 D-isomerase (PGH2), apolipoprotein E (APOE), and clusterin. The cellular functions of these proteins are discussed, along with their relevance in manifesting spondylomyelopathy. However, further studies are warranted, as a lack of human studies is a major limiting factor. Nevertheless, based on the continued progression of the proteomic profile of spondylomyelopathy, new targets can be assessed as candidates for future therapeutic intervention.

Neurocytological Advances in the Treatment of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is an aggressive neoplasm of the brain that has commonly led to disappointing patient outcomes. Despite medical advancements and increasing research efforts, GBM studies reveal a stagnant survival rate at the global level with only sluggish improvement over time. Modern neuro-oncology research places a heavy emphasis on pharmacological therapies. Through a broad database search, we accumulated and synthesized the GBM-related neuroimmunocytological literature to create a comprehensive and contemporary review. Based on our findings, we discuss the recent neurocytological treatment strategies for GMB and the results of the studies. Regorafenib, paxalisib, and dianhydrogalactitol (VAL-083) are showing initial promise to decrease disease progression. VAL-083 is an alkylating agent that creates N7 methylation on DNA and has the ability to cross the blood-brain barrier (BBB). Selinexor, recombinant nonpathogenic polio-rhinovirus, and GBM-vaccine of autologous fibroblasts retrovirally transfected with TFG-IL4-Neo-TK vector have all also shown initial clinical benefit in terms of prolonging survival. Most trials observe modest improvement in outcomes with a positive safety profile. Nevertheless, the need for further studies is warranted, along with the trending of post-therapeutic biomarkers in order to better access future patient outcomes.

Effect of comorbidities on ischemic stroke mortality: An analysis of the National Inpatient Sample (NIS) Database.

BACKGROUND: Stroke risk has been attributed to many pathological and behavioral conditions. Various modifiable and non-modifiable risk factors have been recognized and found consistent throughout epidemiological studies. Herein, we investigate the effect of comorbidities seen with patient's suffering from ischemic stroke and its effect on in-hospital mortality. METHODS: We identified patients >18 year old in the National Inpatient Sample database with diseases of interest utilizing the tenth International Classification of Disease 10 diagnostic codes from the years 2016 to 2018. Interval data were analyzed using one-way ANOVA. Post hoc analysis was performed using Bonferroni correction methods. To determine independent predictors of in-hospital mortality, odds ratios were calculated using binary logistic regression for each comorbidity. Descriptive and numerical statistics, imputation, and logistic regression were calculated using SPSS software version 25. RESULTS: Patients hospitalized with ischemic stroke were found to have the following comorbidities: atrial fibrillation (7.5%), carotid artery stenosis (1.1%), diabetes mellitus type 2 (11.4%), congestive heart failure (CHF) (7.5%), essential hypertension (21.2%), and ischemic heart disease (IHD) (2.3%). In-hospital mortality rates were higher in patients hospitalized with ischemic stroke and concomitant IHD (28.2%, P < 0.001). Hospital length of stay was longest in patients with concomitant CHF (5.96 days, P < 0.001). Similarly, patients with CHF accrued the greatest in-hospital costs (69,174 USD, P < 0.001). CONCLUSION: Patients hospitalized from ischemic stroke suffered from the coexistence of other comorbidities. Of the comorbidities studied, IHD was identified as having the most significant impact on in-hospital mortality.

Genetic Predictors of Early-Onset Spinal Intervertebral Disc Degeneration: Part One of Two.

Intervertebral disc (IVD) degeneration is a progressive and painful pathology that can root from mechanical, biochemical, and environmental stressors. However, recent advancements in biogenetics have now found a predominating genetic influence. Nevertheless, despite these advancements, the pathophysiology of IVD degeneration remains poorly understood. In the first of our two-part series, we will characterize some of the most recent and best-studied genes in the context of intervertebral disc degeneration. We will attempt to formulate the first contemporary gene guide that characterizes the genetic profile of IVD degeneration. The genes of interest include aggrecan (ACAN), matrix metalloproteinase 2 (MMP2), vitamin D receptor (VDR), interleukin 1 alpha (IL1A), and those encoded for collagens such as collagen type XI alpha 1 chain (COL11A1), collagen type I alpha 1 chain (COL1A1), collagen type IX alpha 2 chain (COL9A2), and collagen type IX alpha 3 chain (COL9A3). Genetic analysis studies reveal that these genes play vital roles in maintaining the structural integrity of the intervertebral disc, activating enzymes involved in the extracellular matrix, and promoting connective tissue formation. Nevertheless, characterizing these genes alone is not enough to understand the pathophysiology of IVD degeneration. Therefore, further studies are warranted to understand molecular signalling pathways of IVD degeneration better and ultimately create more sophisticated genetic and cell-based therapies to improve patient outcomes.

Genetic Predictors of Early-Onset Spinal Intervertebral Disc Degeneration: Part Two of Two.

Understanding genetic indicators is a fundamental aspect to characterizing the pathophysiology of chronic diseases such as intervertebral disc degeneration (IVDD). In our previous spinal genetics review, we characterized some more common genetic influencers in the context of IVDD. In this second part of our two-part comprehensive spinal genetics review, we characterize the more infrequently studied genes that have pathophysiological relevance. In doing so, we aim to expand upon the current gene-library for IVDD. The genes of interest include: asporin, cartilage intermediate layer protein, insulin-like growth factor 1 receptor, matrix metallopeptidase 9, and thrombospondin 2. Findings show that these genetic indicators have trends and polymorphisms that may have causal associations with the manifestation of IVDD. However, there is a narrow selection of studies that use genetic indicators to describe correlations to the severity and longevity of the pathology. Nevertheless, with the continued identification of risk genes involved with IVDD, the possibilities for refined models of gene therapies can be established for future treatment trials.

Determination and optimization of ideal patient candidacy for anterior odontoid screw fixation.

BACKGROUND: Odontoid process fractures are one of the most common spine fractures, especially in patients over age 70. There is still much controversy over the ideal candidate for anterior odontoid screw fixation (AOSF), with outcomes affected by characteristics such as fracture morphology, nonideal body habitus, and osteoporosis. Therefore, this systematic review seeks to discuss the optimal criteria, indications, and adverse postoperative considerations when deciding to pursue AOSF. METHODS: This investigation was conducted from experiential recall and article selection performed using the PubMed electronic bibliographic databases. The search yielded 124 articles that were assessed and filtered for relevance. Following the screening of titles and abstracts, 48 articles were deemed significant for final selection. RESULTS: AOSF is often utilized to treat Type IIB odontoid fractures, which has been shown to preserve atlantoaxial motion, limit soft-tissue injuries/blood loss/vertebral artery injury/reduce operative time, provide adequate osteosynthesis, incur immediate spinal stabilization, and allow motion preservation of C1 and C2. However, this technique is limited by patient characteristics such as fracture morphology, transverse ligament rupture, remote injuries, short neck or inability to extend neck, barrel chested, and severe spinal kyphosis, in addition to adverse postoperative outcomes such as dysphagia and vocal cord paralysis. CONCLUSION: Due to the fact that odontoid fractures have a significant morbidity in elderly population, treatment with AOSF is generally recommended for this population with higher risk for nonoperative fusion. Considerations should be made to achieve fracture stability and fusion, while lowering the risk for operative and postoperative complications.

The role of gene therapy as a valuable treatment modality for multiple spinal pathologies.

The world of biomedical research has led to several breakthroughs in the treatment of various spinal pathologies. As we investigate chronic pathologies of the spine, we start to unravel the underlying molecular mechanisms through a careful analysis of mutated genetic sequences. Investigations have led to gene therapy being explored for its potential as a treatment modality. Despite only about 2% of current gene therapy trials being centered for spinal pathologies, spinal diseases are valuable targets in gene therapy administration. Through a comprehensive literature review, our objective is to discuss the molecular mechanisms behind gene therapy for spinal pathologies, the genetic targets, along with the outcomes, success, and possible pitfalls in gene therapy research and administration. The emerging development of robotic technologies and intelligent carriers are recognized as a promising innovative technique for increasing the efficiency of gene therapy and potentially resolving spinal pathologies.

Cerebrolysin for stroke, neurodegeneration, and traumatic brain injury: review of the literature and outcomes.

Cerebrolysin therapy has the potential to significantly aid in the treatment of a wide variety of debilitating neurological diseases including ischemic strokes, neurodegenerative disorders, and traumatic brain injuries. Although Cerebrolysin is not approved for use in the USA, it is used clinically in over 50 countries worldwide. In this review, we focus on outlining the role that Cerebrolysin has in stimulating the molecular signaling pathways that are critical for neurological regeneration and support. An extensive evaluation of these signaling pathways reveals that Cerebrolysin has the potential to intervene in a diverse array of pathophysiological causes of neurological diseases. In the clinical setting, Cerebrolysin is generally safe for human use and has provided functional improvement when used as an adjunct treatment. However, our literature review revealed inconsistent results, as several clinical studies suggested that Cerebrolysin treatment has minor clinical relevance and did not have significant advantages over a placebo. In conclusion, we found that Cerebrolysin therapy can potentially play a major role in the treatment of many neurological diseases. Nevertheless, there remains much to be elucidated about the efficacy of this treatment for specific neurological conditions, and more robust clinical data is needed to reach a consensus and properly define the therapeutic role of Cerebrolysin.

Intramedullary spinal cord cavernous malformations in the pediatric population.

BACKGROUND: Intramedullary spinal cavernous malformations (ISCM) account for just 1% of all intramedullary pediatric spinal cord lesions. Pathologically, they are well-circumscribed vascular malformations that typically appear dark blue or reddish-brown, often coming to the spinal cord surface. With regard to the histopathology findings, ISCMs are comprised sinusoidal vascular spaces lined by a single layer of endothelial cells within a loose connective tissue stroma. As these lesions are often misdiagnosed in the pediatric population, appropriate treatment may be unduly delayed. METHODS: The authors performed an extensive review of the published literature (PubMed) focusing on ISCM in the pediatric age group. RESULTS: The search yielded 17 articles exclusively pertaining to ISCM affecting the pediatric population. CONCLUSION: Here, we reviewed the clinical, radiographic, surgical, and outcome data for the treatment of ISCM in the pediatric age groups. Notably, over 50% of pediatric patients with ISCM experienced an improvement in their neurological status after a mean postoperative follow-up duration of 4 years. Future meta-analyses are needed to highlight the potential presence of ISCM and, thereby, decrease the rate of misdiagnosis of these lesions in the pediatric population presenting with recurrent intramedullary spinal cord hemorrhages.

A Contemporary Review of Neurological Sequelae of COVID-19.

Coronavirus 2019 (COVID-19) is currently the center of what has become a public health crisis. While the virus is well-known for its trademark effects on respiratory function, neurological damage has been reported to affect a considerable proportion of severe cases. To characterize the neuro-invasive potential of this disease, a contemporary review of COVID-19 and its neurological sequelae was conducted using the limited, but growing, literature that is available. These neurological squeal are based on the manifestations that the virus has on normal central and peripheral nervous system function. The authors present the virology of the SARS-CoV-2 agent by analyzing its classification as an enveloped, positive-stranded RNA virus. A comprehensive timeline is then presented, indicating the progression of the disease as a public health threat. Furthermore, underlying chronic neurological conditions potentially lead to more adverse cases of COVID-19. SARS-CoV-2 may reach ACE2 receptors on neuronal tissue through mode of the general circulation. The CNS may also be susceptible to an immune response where a "cytokine storm" can manifest into neural injury. Histological evidence is provided, while symptoms such as headache and vertigo are highlighted as CNS manifestations of COVID-19. Treatment of these symptoms is addressed with paracetamol being recommended as a possible, but not conclusive, treatment to some CNS symptoms. The authors then discuss the peripheral nervous system sequelae and COVID's impact on causing chemosensory dysfunction starting with viral attack on olfactory sensory neurons and cells types within the lining of the nose. Histological evidence is also provided while symptoms such as anosmia and ageusia are characterized as PNS manifestations. Possible treatment options for these symptoms are then addressed as a major limitation, as anecdotal, and not conclusive evidence can be made. Finally, preventive measures of the neurological sequelae are addressed using a multidirectional approach. Postmortem examinations of the brains of COVID-19 patients are suggested as being a possible key to formulating new understandings of its neuropathology. Lastly, the authors suggest a more comprehensive neurological follow-up of recovered patients, in order to better characterize the neurological sequelae of this illness.

Virtual Reality in Neurosurgery: "Can You See It?"-A Review of the Current Applications and Future Potential.

Virtual reality (VR) technology had its early development in the 1960s in the U.S. Air Force and has since evolved into a budding area of scientific research with many practical medical purposes. From medical education to resident training to the operating room, VR has provided tangible benefits to learners and trainees and has also improved surgery through enhanced preoperative planning and efficiency in the operating room. Neurosurgery is a particularly complex field of medicine, in which VR has blossomed into a tool with great usefulness and promise. In spinal surgery, VR simulation has allowed for the practice of innovative minimally invasive procedures. In cranial surgery, VR has excelled in helping neurosurgeons design unique patient-specific approaches to particularly challenging tumor excisions. In neurovascular surgery, VR has helped trainees practice and perfect procedures requiring high levels of dexterity to minimize intraoperative complications and patient radiation exposure. In peripheral nerve surgery, VR has allowed surgeons to gain increased practice and comfort with complex microsurgeries such as nerve decompression. Overall, VR continues to increase its potential in neurosurgery and is poised to benefit patients in a multitude of ways. Although cost-prohibiting, legal, and ethical challenges surrounding this technology must be considered, future research and more direct quantitative outcome comparisons between standard and VR-supplemented procedures would help provide more direction regarding the feasibility of widespread adoption of VR technology in neurosurgery.