The ATP-Binding Cassette Transporter-Mediated Efflux Transport of Ganciclovir at the Blood-Brain Barrier.

Background And Objective: Recent studies have highlighted the key role of the ATP-binding cassette (ABC) transporters, including the P-glycoprotein (P-gp), the breast cancer resistance protein (BCRP), and the multi-drug resistance protein 4 (MRP4) in limiting the brain distribution of several antiviral agents. In this study, we investigated whether the inhibition of these transporters increases the permeability of the blood-brain barrier (BBB) to ganciclovir.

Methods: A microdialysis and high-performance liquid chromatographic method was developed to monitor the concentrations of unbound ganciclovir in the brain interstitial fluid and plasma, with and without the administration of ABC transporter inhibitors.

Clinical features of COVID-19-related encephalitis: comparison with the features of herpes virus encephalitis and autoimmune encephalitis.

Introduction: Identifying coronavirus disease 2019 (COVID-19)-related encephalitis without clear etiological evidence is clinically challenging. The distinctions between this condition and other prevalent encephalitis types remain unknown. Therefore, we aimed to explore the similarities and differences in the clinical characteristics of COVID-19-related encephalitis and other encephalitis types.

Evaluation of metagenomic and pathogen-targeted next-generation sequencing for diagnosis of meningitis and encephalitis in adults: A multicenter prospective observational cohort study in China.

Background: Next-generation sequencing (NGS) might aid in the identification of causal pathogens. However, the optimal approaches applied to cerebrospinal fluid (CSF) for detection are unclear, and studies evaluating the application of different NGS workflows for the diagnosis of intracranial infections are limited.

Methods: In this multicenter, prospective observational cohort study, we described the diagnostic efficacy of pathogen-targeted NGS (ptNGS) and metagenomic NGS (mNGS) compared to that of composite microbiologic assays, for infectious meningitis/encephalitis (M/E).

[Sporadic Creutzfeldt-Jakob Disease With Slow Progression:Report of One Case].

Sporadic Creutzfeldt-Jakob disease(sCJD)is a prion-caused degenerative disease of the central nervous system,with the typical clinical manifestation of rapidly progressive dementia.The course of disease is less than 1 year in most patients and more than 2 years in only 2% to 3% patients.We reported a case of sCJD with expressive language disorder and slow progression in this paper.

Clinical Characteristics and Treatment of Infections in the Central Nervous System.

Purpose: infections are rare in the central nervous system (CNS) and frequently difficult-to-diagnose. Our goal is to assess CNS listeriosis patients' clinical characteristics, diagnosis, treatment, and prognosis.

Patients And Methods: Patients with CNS listeriosis admitted to the Department of neurology, the first medical center of the Chinese PLA general hospital, were enrolled in this study from March 2018 to August 2022.

Multiple drug transporters contribute to the brain transfer of levofloxacin.

Aims: The aim of this study was to assess the influence of the major transporters at blood-brain barrier and blood-cerebrospinal fluid barrier on levofloxacin (LVFX) pharmacokinetics in rat. To explore the different effects of transporters on drug concentrations in cerebrospinal fluid (CSF) and brain extracellular fluid (ECF).

Methods: High-performance liquid chromatography coupled with microdialysis was used to continuously and synchronously measure unbound concentrations of LVFX in rat blood, hippocampal ECF, and lateral ventricle CSF for comprehensive characterization of brain pharmacokinetics.

Proposal of new diagnostic criteria for fatal familial insomnia.

Background: The understanding of fatal familial insomnia (FFI), a rare neurodegenerative autosomal dominant prion disease, has improved in recent years as more cases were reported. This work aimed to propose new diagnostic criteria for FFI with optimal sensitivity, specificity, and likelihood ratio.

Methods: An international group of experts was established and 128 genetically confirmed FFI cases and 281 non-FFI prion disease controls are enrolled in the validation process.

Creutzfeldt-Jakob disease associated with a T188K homozygous mutation in the prion protein gene: a case report and review of the literature.

Genetic Creutzfeldt-Jakob disease (gCJD) is a prion disease caused by mutations in the prion protein gene (). It has an autosomal dominant inheritance, so gCJD with homozygous mutations is extremely rare, and the influence of homozygous mutations on the gCJD phenotype is unknown. We describe the clinical and laboratory features of a patient with a T188K homozygous mutation and perform a literature review of gCJD cases with homozygous mutations.

Acyclovir Brain Disposition: Interactions with P-gp, Bcrp, Mrp2, and Oat3 at the Blood-Brain Barrier.

Background And Objective: Acyclovir is effective in treating herpes simplex virus infections of the central nervous system. The purpose of this study was to investigate the interactions between acyclovir and the efflux pumps P-glycoprotein (P-gp), breast cancer resistance protein (Bcrp), multidrug resistance protein 2 (Mrp2), and organic anion transporter 3 (Oat3) at the blood-brain barrier (BBB).

Methods: Acyclovir concentrations in the blood and brain were evaluated by microdialysis and high-performance liquid chromatography.

Lower motor neuron involvement in patients with neuromyelitis optica spectrum disorders.

Background: Involvement of the central gray matter of spinal cord is a characteristic magnetic resonance imaging (MRI) feature of aquaporin-4-immunoglobulin G antibodies (AQP4-IgG) positive neuromyelitis optica spectrum disorders (NMOSD). However, there has been no systemic electrophysiological study investigating the frequency of lower motor neuron involvement in NMOSD patients.

Methods: We retrospectively reviewed a cohort of 59 NMOSD patients with results of concentric needle electromyography (EMG) and nerve conduction studies (NCS) that were admitted to the Department of Neurology of Chinese PLA General Hospital between January 2016 and December 2019.

Effect of P-glycoprotein Inhibition on the Penetration of Ceftriaxone Across the Blood-Brain Barrier.

Recent studies indicate that inhibition of the efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier (BBB) may represent a putative strategy to increase the BBB penetration of several antibiotics. Therefore, the present study aimed to investigate the effect of P-gp inhibition on the transport of ceftriaxone (CFX) across the BBB. Blood and brain microdialysis in rats was used to monitor blood and brain unbound CFX concentrations following intravenous administration (50 mg/kg), with or without pretreatment with one of the P-gp inhibitors, cyclosporin A (6.

Plaque Length Predicts the Incidence of Microembolic Signals in Acute Anterior Circulation Stroke.

Microembolic signals (MES) of the carotid artery are associated with plaque destabilization and reoccurrence of stroke. Previous studies have focused primarily on the degree of carotid artery stenosis and plaque components, and the relationship between plaque length and microembolic sign has received little attention. We aimed to find the association between carotid plaque length (CPL) and the presence of MES.

Central nervous system aspergillosis in immunocompetent patients: Case series and literature review.

The aim of this study was to investigate the clinical characteristics of central nervous system (CNS) aspergillosis in immunocompetent patients.This study enrolled six immunocompetent patients diagnosed with CNS aspergillosis. Additionally, we reviewed the clinical profiles for 28 cases reported in the literature.

The relationship of leukoaraiosis, haemorrhagic transformation and prognosis at 3 months after intravenous thrombolysis in elderly patients aged ≥ 60 years with acute cerebral infarction.

Backgroud: As the elderly stroke population continues to increase, we will have to confront greater challenges regarding how to choose suitable patients to reduce thrombolysis-related bleeding events and accurately judge their prognosis. Therefore, we evaluated the relationship among leukoaraiosis (LA), haemorrhagic transformation (HT) and the prognosis at 3 months after intravenous (IV) thrombolysis in elderly patients aged ≥ 60 years with acute cerebral infarction (ACI).

Methods: We prospectively and consecutively chose 125 elderly patients aged ≥ 60 years with ACI who could accept and be suitable for IV recombinant tissue plasminogen activator (rtPA) after excluding 6 cases.

Sporadic Creutzfeldt-Jakob Disease: A Retrospective Analysis of 104 Cases.

Background: Sporadic Creutzfeldt-Jakob disease (sCJD) is an extremely rare fatal and infectious neurodegenerative brain disorder characterized by rapidly progressive dementia, cerebellar ataxia, and visual disturbances. This article summarizes the retrospective analysis of 104 sCJD patients in the First Medical Center of Chinese PLA General Hospital from 2003 to 2019.

Methods: A retrospective analysis of the medical records of the 104 patients diagnosed with sCJD was performed from the aspects of demographic data, clinical manifestations, laboratory examinations, cerebrospinal fluid analysis, electroencephalograms (EEGs), diffusion-weighted imaging (DWI) scans, positron emission tomography (PET) scans, and prion protein gene mutations.

Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Encephalitis and Meningitis: A Large, Prospective Case Series of 213 Patients.

We assessed the performance of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis. This was a prospective multicenter study. Cerebrospinal fluid samples from patients with viral encephalitis and/or meningitis, tuberculous meningitis, bacterial meningitis, fungal meningitis, and non-central nervous system (CNS) infections were subjected to mNGS.

Brain Atrophy Associated with Primary Diffuse Meningeal Melanomatosis.

Background: Primary meningeal melanomatosis is a rare leptomeningeal tumor, and the diagnosis is challenging due to nonspecific clinical symptoms and radiologic findings.

Case Description: A 21-year-old man presented with recurrent seizure and impaired memory. Cranial magnetic resonance imaging showed obvious brain atrophy with bilateral extensive meningeal enhancement in the supratentorial region.

Apparent performance of metagenomic next-generation sequencing in the diagnosis of cryptococcal meningitis: a descriptive study.

Introduction: In recent years, metagenomic next-generation sequencing (mNGS) has become widely used in medical microbiology to detect pathogen infection.

Aim: We aimed to assess the diagnostic performance of mNGS of cerebrospinal fluid (CSF) for prediction of cryptococcal meningitis (CM).

Methodology: A comparative evaluation of mNGS (performed on CSF samples) and conventional methods, including India ink staining, culture for fungi and cryptococcal-antigen (CrAg) detection by enzyme immunoassay, was performed on 12 consecutive non-HIV-infected patients with chronic or subacute CM.

Suspected bacterial meningoencephalomyelitis as the trigger or presentation of neuromyelitis optica spectrum disorder flare.

Background: Suspected bacterial meningoencephalomyelitis as the presentation or trigger of neuromyelitis optica spectrum disorders (NMOSD) flare has not been reported in literature.

Case Presentation: A 29 year old female, who has a history of neuromyelitis optica spectrum disorder (NMOSD) for 6 years, presented with symptoms of meningitits, encephalitis, myelitis, headache and fever. Cerebrospinal fluid analysis revealed pleocytosis (1131 × 10/L [83% neutrophils]) and a glucose level of 39.

Neurobrucellosis.

Purpose: Neurobrucellosis (NB) is a rare complication of brucellosis. NB presents with avariety of clinical manifestations, and the symptoms are always atypical. Our aim was to analyze the demographic characteristics, clinical manifestations, laboratory findings, imaging findings, treatments and outcomes of patients with NB.

Effect of Efflux Transporter Inhibition on the Distribution of Fluconazole in the Rat Brain.

Multidrug resistance-associated proteins (MRPs) and organic anion transporters (OATs) are expressed on the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB), preventing the entry of or the pumping out of numerous molecules. Fluconazole is widely used to treat fungal meningoencephalitis. The effect of these transporters on the distribution of fluconazole in the brain is unclear.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): A lymphocytic reactive response of the central nervous system? A case report.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroid (CLIPPERS) was first described in 2010. The characteristic clinical picture, radiological distribution and steroid response have been well-described in previous reports. However, the underlying pathogenesis and nosological position of CLIPPERS in the CNS require further investigation for the primary CNS lymphoma have been identified by autopsy subsequently.