Galantamine-Memantine Combination in the Treatment of Parkinson's Disease Dementia.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects over 1% of population over age 60. It is defined by motor and nonmotor symptoms including a spectrum of cognitive impairments known as Parkinson's disease dementia (PDD). Currently, the only US Food and Drug Administration-approved treatment for PDD is rivastigmine, which inhibits acetylcholinesterase and butyrylcholinesterase increasing the level of acetylcholine in the brain.

The doctor-patient perception mismatch: Improving approaches to assessing outcomes after ischemic stroke treated with reperfusion therapy.

The long-term effects of ischemic stroke on cognition and mental health are not reflected in traditional outcome metrics, like the modified Rankin Scale (mRS) for functional independence. Consequently, this may lead to mismatches in perceptions of overall recovery, despite otherwise qualifying as having good functional outcomes (mRS 0-2). In our multicenter, multinational analysis, we aim to describe the prevalence of, and factors associated with, patient-reported cognitive impairment despite achieving good functional outcomes.

"Chopperlysis": The effect of helicopter transport on reperfusion and outcomes in large vessel occlusion strokes.

Background: In large vessel occlusion (LVO) stroke patients transferred to a comprehensive stroke center for thrombectomy, spontaneous reperfusion may occur during transport, and anecdotally more frequently in patients transferred via helicopter than by ground. This pattern has been more often observed in conjunction with tenecteplase (TNK) treatment prior to helicopter transport. We aim to explore the "chopperlysis" effect-how helicopter transport, particularly with thrombolytics, may affect reperfusion and clinical outcomes.

TRPV4 Channel in Neurological Disease: from Molecular Mechanisms to Therapeutic Potential.

Transient Receptor Potential Vanilloid 4 (TRPV4) is a non-selective cation channel with pivotal roles in various physiological processes, including osmosensitivity, mechanosensation, neuronal development, vascular tone regulation, and bone homeostasis in human bodies. Recent studies have made significant progress in understanding the structure and functional role of TRPV4, shedding light on its involvement in pathological processes, particularly in the realm of neurological diseases. Here, we aim to provide a comprehensive exploration of the multifaceted contributions of TRPV4 to neurological diseases, spanning its intricate molecular mechanisms to its potential as a target for therapeutic interventions.

Development of a 3D Brain Model to Study Sex-Specific Neuroinflammation After Hemorrhagic Stroke.

Subarachnoid hemorrhage (SAH) accounts for 5% of stroke, with women having a decreased inflammatory response compared to men; however, this mechanism has yet to be identified. One hurdle in SAH research is the lack of human brain models. Studies in murine models are helpful, but human models should be used in conjunction for improved translatability.

Brain FADE syndrome: the final common pathway of chronic inflammation in neurological disease.

Importance: While the understanding of inflammation in the pathogenesis of many neurological diseases is now accepted, this special commentary addresses the need to study chronic inflammation in the propagation of cognitive Fog, Asthenia, and Depression Related to Inflammation which we name Brain FADE syndrome. Patients with Brain FADE syndrome fall in the void between neurology and psychiatry because the depression, fatigue, and fog seen in these patients are not idiopathic, but instead due to organic, inflammation involved in neurological disease initiation.

Observations: A review of randomized clinical trials in stroke, multiple sclerosis, Parkinson's disease, COVID, traumatic brain injury, and Alzheimer's disease reveal a paucity of studies with any component of Brain FADE syndrome as a primary endpoint.

Single-cell analysis reveals diversity of tumor-associated macrophages and their interactions with T lymphocytes in glioblastoma.

Glioblastoma (GBM) is an aggressive primary CNS malignancy and clinical outcomes have remained stagnant despite introduction of new treatments. Understanding the tumor microenvironment (TME) in which tumor associated macrophages (TAMs) interact with T cells has been of great interest. Although previous studies examining TAMs in GBM have shown that certain TAMs are associated with specific clinical and/or pathologic features, these studies used an outdated M1/M2 paradigm of macrophage polarization and failed to include the continuum of TAM states in GBM.

In Vitro and In Vivo Drug-Response Profiling Using Patient-Derived High-Grade Glioma.

Background: Genomic profiling cannot solely predict the complexity of how tumor cells behave in their in vivo microenvironment and their susceptibility to therapies. The aim of the study was to establish a functional drug prediction model utilizing patient-derived GBM tumor samples for in vitro testing of drug efficacy followed by in vivo validation to overcome the disadvantages of a strict pharmacogenomics approach.

Methods: High-throughput in vitro pharmacologic testing of patient-derived GBM tumors cultured as 3D organoids offered a cost-effective, clinically and phenotypically relevant model, inclusive of tumor plasticity and stroma.

Upregulation of the Oct3/4 Network in Basal Breast Cancer Is Associated with Its Metastatic Potential and Shows Tissue Dependent Variability.

Adaptive plasticity of Breast Cancer stem cells (BCSCs) is strongly correlated with cancer progression and resistance, leading to a poor prognosis. In this study, we report the expression profile of several pioneer transcription factors of the network associated with tumor initiation and metastasis. In the triple negative breast cancer cell line (MDA-MB-231) stably transfected with human Oct3/4-GFP, differentially expressed genes (DEGs) were identified using qPCR and microarray, and the resistance to paclitaxel was assessed using an MTS assay.

Feasibility Study of Cord Tissue Derived Mesenchymal Stromal Cells in COVID-19-Related Acute Respiratory Distress Syndrome.

Background: Treatment options for patients with COVID-19-related acute respiratory distress syndrome (ARDS) are desperately needed. Allogeneic human umbilical cord derived mesenchymal stromal cells (hCT-MSCs) have potential therapeutic benefits in these critically ill patients, but feasibility and safety data are lacking.

Materials And Methods: In this phase I multisite study, 10 patients with COVID-19-related ARDS were treated with 3 daily intravenous infusions of hCT-MSCs (1 million cells/kg, maximum dose 100 million cells).

Gender differences in Alzheimer's may be associated with TLR4-LYN expression in damage associated microglia and neuronal phagocytosis.

The role of Aβ plaques and neurofibrillary tangles in Alzheimer's disease (AD) pathogenesis have recently come into question due to failure of many pharmaceutical agents targeting these deposits and detection of these misfolded proteins in normal human brains. Therefore, we investigated correlations between microglial activation and toll like receptor 4 (TLR4) and Lck/Yes novel tyrosine (LYN) kinase signaling in an AD mouse model. In this study, we used 5-6-month-old 5XFAD and wild type (WT) male and female mice.

Acute subdural hematoma due to acute myeloid leukemia and B-cell lymphoma.

Chloroma, is an rare malignant tumor characterized by the extramedullary blast proliferation of myeloid lineages that subsequently change the normal architecture of surrounding tissues. Because this is very rare disease, primary central nervous system myeloid sarcoma has not been widely reported. Myeloid sarcoma, as a group of heterogenetic diseases, presents with differential clinical and histological pictures depending upon the primary affected site.

Posterior reversible encephalopathy syndrome due to unilateral renal artery stenosis: A case report.

A tricenarian female with a past medical history of status epilepticus secondary to posterior reversible encephalopathy syndrome (PRES) of unknown etiology presented with a 2-week history of double vision, dizziness, elevated blood pressure, and altered mental status. On hospital day 2, she experienced status epilepticus, during which her blood pressure rose to 240/160 from her baseline of around 140/90. The patient was subsequently intubated for airway protection and transferred to the intensive care unit, where she was started on a nicardipine drip.

An overview on microglial origin, distribution, and phenotype in Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease that is responsible for about one-third of dementia cases worldwide. It is believed that AD is initiated with the deposition of Ab plaques in the brain. Genetic studies have shown that a high number of AD risk genes are expressed by microglia, the resident macrophages of brain.

Microglial TLR4 is Critical for Neuronal Injury and Cognitive Dysfunction in Subarachnoid Hemorrhage.

Background: Toll-like receptor 4 (TLR4) activation causes excessive production of proinflammatory mediators and an increased expression of costimulatory molecules that leads to neuroinflammation after subarachnoid hemorrhage (SAH). Although TLR4-mediated inflammatory pathways have long been studied in neuroinflammation, the specific glia implicated in initiation and propagation of neuroinflammation in SAH have not been well elucidated. In this study, we investigated the involvement of glial TLR4 including microglia and astrocytes in brain damage and poor neurological outcome.

Multiple watershed and cardioembolic strokes in 84-year-old male after cardiac ablation procedure: Case report.

Current guidelines do not include radiologic assessment of the carotid arteries before catheter ablation procedures. There are multiple studies describing the risks of periprocedural cardioembolic strokes during cardiac ablation procedure but none describing the risks of periprocedural watershed strokes due to hypoperfusion during cardiac ablation. It is critically important for neurologists, cardiologists, and all other associated health-care workers to recognize the risks of neurologic complications, such as watershed strokes, before cardiac procedures are performed.

Sodium Variability and Probability of Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage.

Objectives: Vasospasm is a well-known complication of aneurysmal subarachnoid hemorrhage (aSAH) that generally occurs 4-14 days post-hemorrhage. Based on American Heart Association guidelines, the current understanding is that hyponatremic episodes may lead to vasospasm. Therefore, we sought to determine the association between repeated serum sodium levels of aSAH patients and its relationship to radiographic vasospasm.

Post-stroke recrudescence-a possible connection to autoimmunity?

Early recanalization of the occluded vessel is the only efficient intervention that improves outcome after ischemic stroke. In contrast, interventions for chronic issues facing stroke patients are limited. Recent clinical and preclinical studies have shown a correlation between upregulated immune responses to brain antigens and post-stroke recrudescence (PSR), post-stroke fatigue (PSF), and dementia (PSD); all of which are associated with poor long-term stroke outcome.

Gliomagenesis is orchestrated by the Oct3/4 regulatory network.

Background: Glioblastoma multiforme (GBM) is a lethal brain tumor characterized by developmental hierarchical phenotypic heterogeneity, therapy resistance and recurrent growth. Neural stem cells (NSCs) from human central nervous system (CNS), and glioblastoma stem cells from patient-derived GBM (pdGSC) samples were cultured in both 2D well-plate and 3D monoclonal neurosphere culture system (pdMNCS). The pdMNCS model shows promise to establish a relevant 3D-tumor environment that maintains GBM cells in the stem cell phase within suspended neurospheres.

Effects of Volatile Anesthetics on Postoperative Ischemic Stroke Incidence.

Background Preclinical studies suggest that volatile anesthetics decrease infarct volume and improve the outcome of ischemic stroke. This study aims to determine their effect during noncardiac surgery on postoperative ischemic stroke incidence. Methods and Results This was a retrospective cohort study of surgical patients undergoing general anesthesia at 2 tertiary care centers in Boston, MA, between October 2005 and September 2017.

Defining the Mechanism of Subarachnoid Hemorrhage-Induced Pyrexia.

Fever can affect the majority of patients with subarachnoid hemorrhage (SAH) and many times no identifiable source is found for the fever whether infectious or sterile, like deep vein thrombosis. We hypothesized that fever in SAH is mediated by a NON-cyclo-oxygenase-dependent mechanism, which we neologized as subarachnoid hemorrhage-induced pyrexia (SAHiP). This hypothesis was investigated using genetically modified mice, pharmacological manipulation, cerebrospinal fluid from SAH patients, and a large cohort of SAH patients.

Effect of Blood Pressure Variability During the Acute Period of Subarachnoid Hemorrhage on Functional Outcomes.

Background: The association of blood pressure variation with poor outcomes in aneurysmal subarachnoid hemorrhage (aSAH) is unknown.

Objective: To evaluate the association of systolic blood pressure (SBP) variation and clinical outcomes in aSAH.

Methods: We conducted a retrospective chart review of all aSAH patients treated at an academic institution between 2007 and 2016.