The AANS Harvey Cushing Medal: a demographic and academic analysis of its recipients.

Background: The Harvey Cushing Medal, awarded by the American Association of Neurological Surgeons, is the premier accolade in neurosurgery. The study's purpose was to examine the qualities and accomplishments of previous winners, emphasizing potential selection biases, with the aim to promote social justice and guide young neurosurgeons in their career paths. Results: Predominantly, recipients graduated from top-ranked United States News and World Report institutions and specialized in cerebrovascular and neuro-oncologic/skull base neurosurgery. A significant proportion held roles as department or division chairs and led neurosurgical organizations. All awardees were male, and there was a notable trend of increasing publication counts among more recent recipients. Conclusions: Commonalities among Harvey Cushing Medal winners include graduating from top institutions, holding significant leadership roles, and having an extensive publication history. However, the absence of female and underrepresented minority awardees underscores an urgent need for greater diversity in the selection process.

Meta-analysis of the role of neutrophil to lymphocyte ratio in neonatal sepsis.

INTRODUCTION: The neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, measures innate-adaptive immune system balance. In this systematic review and meta-analysis, we aim to analyze the current literature to evaluate the diagnostic role of NLR in neonatal sepsis. METHODS: PubMed, Web of Science, and Scopus were used to conduct a systematic search for relevant publications published before May 14, 2022. RESULTS: Thirty studies, including 2328 neonates with sepsis and 1800 neonates in the control group, were included in our meta-analysis. The results indicated that NLR is higher in neonates with sepsis compared to healthy controls (SMD = 1.81, 95% CI = 1.14-2.48, P-value < 0.001) in either prospective (SMD = 2.38, 95% CI = 1.40-3.35, P-value < 0.001) or retrospective studies (SMD = 0.87, 95% CI = 0.63-1.12, P-value < 0.001) with a pooled sensitivity of 79% (95% CI = 62-90%), and a pooled specificity of 91% (95% CI = 73-97%). Also, we found that NLR is higher in neonates with sepsis compared to those who were suspected of sepsis but eventually had negative blood cultures (SMD =1.99, 95% CI = 0.76-3.22, P-value = 0.002) with a pooled sensitivity of 0.79% (95% CI = 0.69-0.86%), and a pooled specificity of 73% (95% CI = 54-85%). In addition, neonates with sepsis had elevated levels of NLR compared to other ICU admitted neonates (SMD = 0.73, 95% CI = 0.63-0.84, P < 0.001). The pooled sensitivity was 0.65 (95% CI, 0.55-0.80), and the pooled specificity was 0.80 (95% CI, 0.68-0.88). CONCLUSION: Our findings support NLR as a promising biomarker that can be readily integrated into clinical settings to aid in diagnosing neonatal sepsis. As evidenced by our results, restoring balance to the innate and adaptive immune system may serve as attractive therapeutic targets. Theoretically, a reduction in NLR values could be used to measure therapeutic efficacy, reflecting the restoration of balance within these systems.

Encephalitis and Meningitis: Indications for Intervention.

Meningitis and encephalitis are characterized by inflammation of the meninges and brain parenchyma, respectively. The blood-brain barrier normally acts as a protective barrier against inflammation in the central nervous system (CNS), but its compromise requires prompt diagnosis and treatment to prevent morbidity and mortality. Optimizing therapy for meningitis and encephalitis can expedite resolution of symptoms, mitigating the risk of neuronal injury and minimizing potential long-term neurological sequelae. This paper aims to provide a comprehensive overview of the etiology and pathophysiology of meningitis and encephalitis, discussing the diagnostic criteria, and emphasizing the clinical indications for treatments, including current treatment strategies, and emerging therapeutic approaches.

Innovative Approaches for Breast Cancer Metastasis to the Brain.

Breast cancer metastasis is a continued concern for patients with recent development in our understanding of disease progression. In this paper, we highlight the pathophysiology behind breast cancer metastasis. Blood brain barrier disruption plays a critical component in progression. We then investigate the current treatment strategies and recommended guidelines. This focuses on radiation and medical management. Finally, we address the role of surgical intervention. The data is organized into tables and figures to highlight key components. Finally, we address emerging treatments and pre-clinical data. The paper will serve as a user-friendly guide for clinicians and researchers to help formulate a strategy to manage breast cancer metastasis patients sufficiently.

Focused Delivery of Chemotherapy to Augment Surgical Management of Brain Tumors.

Chemotherapy as an adjuvant therapy that has largely failed to significantly improve outcomes for aggressive brain tumors; some reasons include a weak blood brain barrier penetration and tumor heterogeneity. Recently, there has been interest in designing effective ways to deliver chemotherapy to the tumor. In this review, we discuss the mechanisms of focused chemotherapies that are currently under investigation. Nanoparticle delivery demonstrates both a superior permeability and retention. However, thus far, it has not demonstrated a therapeutic efficacy for brain tumors. Convection-enhanced delivery is an invasive, yet versatile method, which appears to have the greatest potential. Other vehicles, such as angiopep-2 decorated gold nanoparticles, polyamidoamine dendrimers, and lipid nanostructures have demonstrated efficacy through sustained release of focused chemotherapy and have either improved cell death or survival in humans or animal models. Finally, focused ultrasound is a safe and effective way to disrupt the blood brain barrier and augment other delivery methods. Clinical trials are currently underway to study the safety and efficacy of these methods in combination with standard of care.

Multimodal detection of dopamine by sniffer cells expressing genetically encoded fluorescent sensors.

Dopamine supports locomotor control and higher brain functions such as motivation and learning. Consistently, dopaminergic dysfunction is involved in a spectrum of neurological and neuropsychiatric diseases. Detailed data on dopamine dynamics is needed to understand how dopamine signals translate into cellular and behavioral responses, and to uncover pathological disturbances in dopamine-related diseases. Genetically encoded fluorescent dopamine sensors have recently enabled unprecedented monitoring of dopamine dynamics in vivo. However, these sensors' utility for in vitro and ex vivo assays remains unexplored. Here, we present a blueprint for making dopamine sniffer cells for multimodal dopamine detection. We generated sniffer cell lines with inducible expression of seven different dopamine sensors and perform a head-to-head comparison of sensor properties to guide users in sensor selection. In proof-of-principle experiments, we apply the sniffer cells to record endogenous dopamine release from cultured neurons and striatal slices, and for determining tissue dopamine content. Furthermore, we use the sniffer cells to measure dopamine uptake and release via the dopamine transporter as a radiotracer free, high-throughput alternative to electrochemical- and radiotracer-based assays. Importantly, the sniffer cell framework can readily be applied to the growing list of genetically encoded fluorescent neurotransmitter sensors.

Pediatric Subarachnoid Hemorrhage: Rare Events with Important Implications.

Rupture of an aneurysm is the leading cause of subarachnoid hemorrhage (SAH) which results in accumulation of blood between the arachnoid and pia mater, consequently increasing intracranial pressure. This often results in life threatening conditions like herniation or clinical presentations including focal neurological deficits. In children, these events, although rare, have significant implications. Pediatric SAH is associated with better outcomes in the hospital setting and may even be prevented proactively by the recognition of potential risk factors. Specifically, better recognition of genetic predispositions, metastatic lesions, and infectious causes of aneurysms is important to understand their growth and prevent hemorrhagic events. This review highlights the causes of pediatric SAH, reviews the models of current understanding of this etiology, and discusses the current treatment schema to provide a succinct summary and highlight gaps in current knowledge. This may lead to future investigations aimed at further improving prevention strategies, patient care, and patient outcomes.

Examining the role of astrogliosis and JNK signaling in post-traumatic epilepsy.

OBJECTIVE: Post-traumatic epilepsy is a devastating complication of traumatic brain injury that has no targeted pharmacological therapy. Previous literature has explored the role of the c-Jun N-terminal kinase (JNK) pathway in epilepsy and the creation of epileptogenic foci by reactive astrogliosis; however, the relationship between reactive astrogliosis and the c-Jun N-terminal kinase signaling pathway in the development of post-traumatic epilepsy has not been thoroughly examined. METHODS: Four experimental groups, consisting of c57/b16 male mice, were examined: (1) control, (2) traumatic brain injury of graded severity (mild, moderate, severe), (3) sub-convulsive kainic acid alone without traumatic brain injury (15 mg/kg i.p.), and (4) sub-convulsive kainic acid administered 72 h after moderate traumatic brain injury. Modified Racine scale from 1 to 72 h and total beam breaks at 72 h were used to assess seizure activity. Immunohistochemistry and western blot were utilized to examine astrogliosis (GFAP), microglia activation (IBA-1), and phosphorylated JNK in prefrontal cortex samples collected from the contracoup side at 72 h post-injury. RESULTS: Astrogliosis, measured by GFAP, was increased after traumatic brain injury and increased commensurately based on the degree of injury. Mice with traumatic brain injury demonstrated a four-fold increase in phosphorylated JNK: p < 0.001. Sub-convulsive kainic acid administration did not increase seizure activity nor phosphorylation of JNK in mice without traumatic brain injury; however, sub-convulsive kainic acid administration in mice with moderate traumatic brain injury did increase phosphorylated JNK. Seizure activity was worse in mice, with traumatic brain injury, administered kainic acid than mice administered kainic acid. CONCLUSIONS: Reactive astrocytes may have dysfunctional glutamate regulation causing an increase in phosphorylated JNK after kainic acid administration. Future studies exploring the effects of JNK inhibition on post-traumatic epilepsy are recommended.

Utilization of EEG for Monitoring in Subarachnoid hemorrhage Recovery.

Seizures and delayed cerebral ischemia following subarachnoid hemorrhage are associated with significant morbidity and mortality. In this article, we briefly review subarachnoid hemorrhage, its complications, and the current literature on information gained from EEG monitoring in subarachnoid hemorrhage. We review when EEG should be used implemented in the multi-modal monitoring of patients with subarachnoid hemorrhage. Finally, we discuss the recent advances and future directions in the field.

Management of Neuropsychiatric Symptoms for Chronic Traumatic Encephalopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repeated head injury. The common presenting neuropsychiatric manifestations and diagnostic strategies for early diagnosis and subsequent treatment will be reviewed. This article discusses methods for injury prevention, risk assessment, and methods for supportive symptom management including lifestyle modifications, physical, occupational, and neurorehabilitation, and pharmaceutical management. Lastly, we propose the use of assessment tools validated for other neurodegenerative disorders in CTE to establish a baseline, track outcomes, and measure improvement in this population.

α-Synuclein-induced dysregulation of neuronal activity contributes to murine dopamine neuron vulnerability.

Pathophysiological damages and loss of function of dopamine neurons precede their demise and contribute to the early phases of Parkinson's disease. The presence of aberrant intracellular pathological inclusions of the protein α-synuclein within ventral midbrain dopaminergic neurons is one of the cardinal features of Parkinson's disease. We employed molecular biology, electrophysiology, and live-cell imaging to investigate how excessive α-synuclein expression alters multiple characteristics of dopaminergic neuronal dynamics and dopamine transmission in cultured dopamine neurons conditionally expressing GCaMP6f. We found that overexpression of α-synuclein in mouse (male and female) dopaminergic neurons altered neuronal firing properties, calcium dynamics, dopamine release, protein expression, and morphology. Moreover, prolonged exposure to the D2 receptor agonist, quinpirole, rescues many of the alterations induced by α-synuclein overexpression. These studies demonstrate that α-synuclein dysregulation of neuronal activity contributes to the vulnerability of dopaminergic neurons and that modulation of D2 receptor activity can ameliorate the pathophysiology. These findings provide mechanistic insights into the insidious changes in dopaminergic neuronal activity and neuronal loss that characterize Parkinson's disease progression with significant therapeutic implications.