CNS disease

IMPORTANCE: Evidence supports using antiplatelet therapy in patients with acute ischemic stroke. However, neurological deterioration remains common under the currently recommended antiplatelet regimen, leading to poor clinical outcomes. OBJECTIVE: To determine whether intravenous tirofiban administered within 24 hours of stroke onset prevents early neurological deterioration in patients with acute noncardioembolic stroke compared with oral aspirin. DESIGN, SETTING, AND PARTICIPANTS: This investigator-initiated, multicenter, open-label, randomized clinical trial with blinded end-point assessment was conducted at 10 comprehensive stroke centers in China between September 2020 and March 2023...

Organoids have emerged as robust tools for unravelling the mechanisms that underly tissue development. They also serve as important in vitro systems for studying fundamentals of stem cell behavior and for building advanced disease models. During early development, a crucial step in the formation of the central nervous system is patterning of the neural tube dorsal-ventral (DV) axis. Here we describe a simple and rapid culture protocol to produce human neuroepithelial (NE) cysts and DV-patterned organoids from single human-induced pluripotent stem cells (hiPSCs)...

PURPOSE: Von Hippel-Lindau (VHL) disease is an autosomal-dominantly inherited tumor predisposition syndrome. One of the most common tumors are central nervous system (CNS) hemangioblastomas. Recommendations on the initiation and continuation of the screening and surveillance program for CNS tumors in pediatric VHL patients are based on small case series and thus low evidence level. To derive more robust screening recommendations, we report on the largest monocentric pediatric cohort of VHL patients...

Parechovirus A (PeV-A) infections have been detected with increasing frequency in US infants under 6 months of age, leading to a Centers for Disease Control and Prevention (CDC) health advisory in July 2022. Clinicians are advised to consider PeV-A laboratory testing of blood and cerebrospinal fluid when infants present with unexplained fever, sepsis-like illness, or neurological issues. Clinical laboratories are encouraged to offer in-house molecular testing for PeV-A to avoid diagnostic delays, unnecessary use of antibiotics, and prolonged hospitalization of infants presenting with sepsis-like illness...

Nocardia is a rare cause of ocular infections and most commonly occurs secondary to trauma. Systemic Nocardiosis may have ocular involvement in rare cases. We report a case of disseminated nocardiosis with orbital apex involvement and endophthalmitis in an immunocompromised patient. The patient presented with respiratory sepsis, and later developed complete ptosis and ophthalmoplegia in the left eye. This was on the background of treatment with high-dose prednisolone. Magnetic resonance imaging showed enhancement of the entire clivus, extending into the left orbital apex and cavernous sinus...

Neuroinflammation, blood-brain barrier (BBB) dysfunction, neuron and glia injury/death and myelin damage are common central nervous system (CNS) pathologies observed in various neurological diseases and injuries. Serine protease inhibitor (Serpin) clade A member 3n (Serpina3n), and its human orthologue SERPINA3, is an acute-phase inflammatory glycoprotein secreted primarily by the liver into the bloodstream in response to systemic inflammation. Clinically, SERPINA3 is dysregulated in brain cells, cerebrospinal fluid and plasma in various neurological conditions...

BACKGROUND: Optic neuritis (ON) is a common feature of inflammatory demyelinating diseases (IDDs) such as multiple sclerosis (MS), aquaporin 4-antibody neuromyelitis optica spectrum disorder (AQP4 + NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, the involvement of the optic chiasm (OC) in IDD has not been fully investigated. AIMS: To examine OC differences in non-acute IDD patients with (ON+) and without ON (ON-) using magnetisation transfer ratio (MTR), to compare differences between MS, AQP4 + NMOSD and MOGAD and understand their associations with other neuro-ophthalmological markers...

BACKGROUND: This study investigates clinical and biomarker differences between standard interval dosing (SID) and extended interval dosing (EID) of ocrelizumab therapy in multiple sclerosis (MS). METHODS: This is a prospective, double-arm, open-label, multi-center study in Denmark. Participants diagnosed with MS on ocrelizumab therapy >12 months were included ( n = 184). Clinical, radiological, and blood-based biomarker outcomes were evaluated. MRI disease activity, relapses, worsening of neurostatus, and No Evidence of Disease Activity-3 (NEDA-3) were used as a combined endpoint...

The coordinated action of multiple leg joints and muscles is required even for the simplest movements. Understanding the neuronal circuits and mechanisms that generate precise movements is essential for comprehending the neuronal basis of the locomotion and to infer the neuronal mechanisms underlying several locomotor-related diseases. Drosophila melanogaster provides an excellent model system for investigating the neuronal circuits underlying motor behaviors due to its simple nervous system and genetic accessibility...

Central nervous system disorders are prevalent, profoundly debilitating, and poorly managed. Developing innovative treatments for these conditions, including Alzheimer's disease, could significantly improve patients' quality of life and reduce the future economic burden on healthcare systems. However, groundbreaking drugs for central nervous system disorders have been scarce in recent years, highlighting the pressing need for advancements in this field. One significant challenge in the realm of nanotherapeutics is ensuring the precise delivery of drugs to their intended targets due to the complex nature of Alzheimer's disease...

HIV-infection of microglia and macrophages (MMs) induces neuronal injury and chronic release of inflammatory stimuli through direct and indirect molecular pathways. A large percentage of people with HIV-associated neurologic and psychiatric co-morbidities have high levels of circulating inflammatory molecules. Microglia, given their susceptibility to HIV infection and long-lived nature, are reservoirs for persistent infection. MMs and neurons possess the molecular machinery to detect pathogen nucleic acids and proteins to activate innate immune signals...

INTRODUCTION: Acute Necrotizing Encephalopathy (ANE), is a kind of severe Central Nervous System Disease. The commonest pathogen is the influenza virus. The pathogenesis of ANE is bound up to genetic susceptibility and cytokine storm. Interleukin-6 (IL-6) is deemed as the core function in cytokine storm of ANE and that plays a significant role in evaluating the severity of Influenza-Related ANE. Tocilizumab, an IL-6 antagonist, is known to be safe and effective in the treatment of ANE when used early and has an essential role in improving prognosis and preventing disability...

Background The coronavirus disease 2019 (COVID-19) pandemic provoked disruptions in healthcare delivery. Following the recommendations of major surgical societies and surgical departments globally, most surgeries were widely canceled or postponed, causing significant disruptions to healthcare delivery worldwide, including in Brazil. Brazil's public healthcare system - Sistema Único de Saúde (SUS) was particularly affected, with a substantial decline in elective procedures, especially during the pandemic's early stages...

Rabies is an acute fatal disease of the central nervous system. Neuroimaging plays an important role, especially in establishing an early diagnosis and distinguishing it from other types of encephalitis. This case report aims to give a brief review of this condition and report the less common MRI findings of the disease. We herein report a case of a 61-year-old male bitten by a stray dog who presented with fever, vomiting, headache, sialorrhea, dysarthria, dysphagia, and upper limb weakness which progressed to lower limbs on the next day...

Sleep is an essential activity for the survival of mammals. Good sleep quality helps promote the performance of daily functions. In contrast, insufficient sleep reduces the efficiency of daily activities, causes various chronic diseases like Alzheimer's disease, and increases the risk of having accidents. The GABAergic system is the primary inhibitory neurotransmitter system in the central nervous system. It transits the gamma-aminobutyric acid (GABA) neurotransmitter via GABAA and GABAB receptors to counterbalance excitatory neurotransmitters, such as glutamate, noradrenaline, serotonin, acetylcholine, orexin, and dopamine, which release and increase arousal activities during sleep...

ABSTRACT: The current work presents a novel flexible multifunctional platform for biological interface applications. The use of titania nanotube arrays (TNAs) as a multifunctional material is explored for soft-tissue interface applications. In vitro biocompatibility of TNAs to brain-derived cells was first examined by culturing microglia cells-the resident immune cells of the central nervous system on the surface of TNAs. The release profile of an anti-inflammatory drug, dexamethasone from TNAs-on-polyimide substrates, was then evaluated under different bending modes...

Transcranial ultrasonic neuromodulation is a rapidly burgeoning field where low-intensity transcranial focused ultrasound (tFUS), with exquisite spatial resolution and deep tissue penetration, is used to non-invasively activate or suppress neural activity in specific brain regions. Over the past decade, there has been a rapid increase of tFUS neuromodulation studies in healthy humans and subjects with central nervous system (CNS) disease conditions, including a recent surge of clinical investigations in patients...

BACKGROUND: Emerging risk factors highlight the need for an updated understanding of cryptococcosis in the United States. OBJECTIVE: Describe the epidemiological trends and clinical outcomes of cryptococcosis in three patient groups: people with HIV (PWH), non-HIV-infected and non-transplant (NHNT) patients, and patients with a history of solid organ transplantation. METHODS: We utilized data from the Merative Medicaid Database to identify individuals aged 18 and above with cryptococcosis based on the International Classification of Diseases, Tenth Revision diagnosis codes from January 2017 to December 2019...

Glia derived secretory factors play diverse roles in supporting the development, physiology, and stress responses of the central nervous system (CNS). Through transcriptomics and imaging analyses, we have identified Obp44a as one of the most abundantly produced secretory proteins from Drosophila CNS glia. Protein structure homology modeling and Nuclear Magnetic Resonance (NMR) experiments reveal Obp44a as a fatty acid binding protein (FABP) with a high affinity towards long-chain fatty acids in both native and oxidized forms...

Brain endothelial cells (BECs) play an important role in maintaining central nervous system (CNS) homeostasis through blood-brain barrier (BBB) functions. BECs express low baseline levels of adhesion receptors, which limits entry of leukocytes. However, the molecular mediators governing this phenotype remain mostly unclear. Here, we explored how infiltration of immune cells across the BBB is influenced by the scaffold protein IQ motif containing GTPase activating protein 2 (IQGAP2). In mice and zebrafish, we demonstrate that loss of Iqgap2 increases infiltration of peripheral leukocytes into the CNS under homeostatic and inflammatory conditions...