Histiocytic sarcoma (HS) rarely affects the central nervous system (CNS) and often presents with nonspecific neurological symptoms, making diagnosis challenging. We report, to our knowledge, the first case of CNS-HS with concurrent skull base infiltration and intraventricular dissemination, highlighting the diagnostic challenges of this aggressive disease. An 18-year-old woman with a 9-month history of progressive headaches and seizures was initially misdiagnosed with viral meningitis. She subsequently underwent brain magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and neuroendoscopic biopsy via a lateral ventricle approach to establish a definitive diagnosis. MRI revealed a lesion in the right medial temporal lobe with extensive skull base infiltration and intraventricular dissemination. CSF analysis demonstrated hypoglycorrhachia (low CSF glucose) and elevated protein levels without pleocytosis. Histopathology confirmed HS, with tumor cells strongly positive for CD68 and CD163. This case illustrates the diagnostic challenges of CNS-HS and underscores the importance of advanced neuroimaging, metabolic CSF analysis, and early biopsy in patients with atypical neurological presentations. Given the rapid progression and poor prognosis, early recognition and comprehensive molecular profiling may facilitate targeted therapies.

The pathogenicity of variants of uncertain significance in the LRRK2 gene remains underexplored. Investigating the LRRK2 variant spectrum in a large Chinese population cohort can provide deeper insights into its pathogenic mechanisms. This study examined the LRRK2 gene variants in 20,519 Chinese individuals, including 7,562 Parkinson’s disease (PD) patients, 3,077 Essential tremor (ET) patients, and 9880 healthy controls. We conducted a genetic analysis of low-frequency and common non-synonymous variants in the LRRK2 gene across the cohorts. A total of 287 low-frequency non-synonymous LRRK2 variants were identified in the PD and control cohorts. Among these, six reported pathogenic variants (p.R1325Q, p.R1441C, p.R1441H, p.V1447M, p.G2019S, p.I2020T) and three reported likely pathogenic variants (p.R1067Q, p.N1437D, p.R1728H) were enriched in PD cases, with a frequency of 0.71%. In contrast, only one pathogenic variant (p.R1325Q) and one likely pathogenic variant (p.R1067Q) were observed in healthy controls (0.11%), and the ET cohort exhibited similar variant distribution to controls (0.19%). Burden analysis and association analysis revealed novel likely pathogenic variants, including p.A312V, p.M968K, and p.R1320S as candidates. These novel variants were significantly more frequent in PD patients (0.79%) compared to healthy controls (0.20%) or ET patients (0.42%). Additionally, seven common missense variants of LRRK2 were identified, and significant associations with PD for p.A419V, p.R1628P, and p.G2385R were confirmed, but no common variants were linked to ET. This study provides the first comprehensive characterization of the LRRK2 variant spectrum in a large Chinese population, underscoring the pivotal role of LRRK2 in PD pathogenesis but not in ET. These findings advance the understanding of LRRK2 in neurodegenerative disorders and lay a foundation for personalized therapeutic strategies based on genetic profiling.

Background:Intracranial infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) pose significant therapeutic challenges, primarily due to the limited penetration of antimicrobial agents across the blood-brain barrier. Ceftazidime/avibactam demonstrates efficacy against multidrug-resistant Gram-negative pathogens. However, its CSF pharmacokinetics and optimal dosing in patients with augmented renal clearance (ARC; CrCl > 130 mL/min/1.73 m²) remain inadequately characterized. Methods:We utilized validated high-performance liquid chromatography to quantify ceftazidime/avibactam concentrations in paired plasma and CSF samples obtained from a traumatic brain injury patient with CRKP ventriculitis and ARC (CrCl 154.37 mL/min/1.73 m²). The MIC of ceftazidime/avibactam was determined using broth microdilution in accordance with Clinical and Laboratory Standards Institute guidelines. Results:Standard Ceftazidime/avibactam dosing (2.5 g q8h) resulted in subtherapeutic trough concentrations in both plasma (ceftazidime/avibactam: 10.39/0.96 µg/mL) and CSF (ceftazidime/avibactam: 20.4/0.68 µg/mL) against the target pathogen (MIC = 4 mg/L). Dose intensification to 2.5 g q6h administered via 3-h prolonged infusion achieved supra-therapeutic exposures (troughs: plasma 65.60/8.70 µg/mL; CSF 58.90/10.82 µg/mL; CSF/plasma ratio = 0.9 for ceftazidime), which correlated with CSF sterilization and resolution of inflammatory markers. Conclusion:This first-in-human pharmacokinetic evidence in a patient with ARC underscores the inadequacy of conventional ceftazidime/avibactam regimens in this population. Our findings advocate for therapeutic drug monitoring-guided dose optimization incorporating extended infusions to achieve therapeutic targets. These results emphasize the critical need for personalized dosing algorithms in the neurocritical care setting.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. PD patients exhibit varying degrees of abnormal glucose metabolism throughout disease stages. Abnormal glucose metabolism is closely linked to the PD pathogenesis and progression. Key glucose metabolism processes involved in PD include glucose transport, glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, the pentose phosphate pathway, and gluconeogenesis. Recent studies suggest that glucose metabolism is a potential therapeutic target for PD. In this review, we explore the connection between PD and abnormal glucose metabolism, focusing on the underlying pathophysiological mechanisms. We also summarize potential therapeutic drugs related to glucose metabolism based on results from current cellular and animal model studies.

BACKGROUND:Adrenoleukodystrophy (ALD) is a rare X-linked genetic metabolic disorder characterized by the accumulation of very long chain fatty acids (VLCFA) within the adrenal glands, as well as the central and peripheral nervous systems. Adult-onset ALD is particularly uncommon and easily misdiagnosed. The objective of this study is to facilitate the early diagnosis and treatment of adult-onset ALD. CASE PRESENTATION:Seven adult-onset ALD patients of Chinese descent were enrolled in the study. Detailed clinical characteristics, laboratory results, imaging findings and genetic testing of the patients were collected and analyzed. All seven patients diagnosed with adult-onset ALD were male, including two with adult cerebral ALD (ACALD), one with adrenomyeloneuropathy (AMN), and four presenting with the spinocerebellar variant. The primary clinical manifestations of the two ACALD patients were progressive cognitive dysfunction and psychiatric symptoms. The AMN patient showed chronic progressive spastic paraplegia and displayed non-specific thoracic spinal cord atrophy on MRI. Symptoms observed in the four patients with spinocerebellar variant included cerebellar ataxia, dysarthria, spastic paraplegia, peripheral neuropathy, sphincter dysfunction, and alopecia. These four patients all demonstrated symmetrical white matter hyperintensity (WMH) in the cerebellum on brain magnetic resonance imaging (MRI). Additionally, two of these patients exhibited abnormal MRI signals in the pyramidal tract. All the patients had an elevation of VLCFAs, which is diagnostic for ALD. One patient exhibited elevated adrenocorticotropic hormone (ACTH) and decreased cortisol levels, while six patients displayed slightly elevated ACTH levels and normal cortisol levels without any clinical signs of adrenal insufficiency. Genetic testing identified four known ABCD1 pathogenic variants as well as two novel pathogenic variants. CONCLUSIONS:Progressive cognitive impairment and behavioral abnormalities are common clinical manifestations of ACALD. AMN and the spinocerebellar variant are prevalent phenotypes of adult-onset ALD. Patients with adult-onset ALD may present with isolated WMH in the cerebellum on brain MRI. Routine screening for ALD should be conducted in male patients diagnosed with Addison's disease. Subclinical adrenal cortex insufficiency is a common finding in adult-onset ALD. Elevated levels of VLCFA function as a reliable clinical biomarker for ALD. The identification of novel pathogenic variants in ABCD1 broadens the genetic spectrum of ALD.

This study aims to explore the predictors of poor outcomes by analyzing the clinical characteristics and prognosis of adult patients with severe forms of autoimmune encephalitis (AE) requiring intensive care unit (ICU) admission. A retrospective analysis was conducted on 134 adult patients diagnosed with definite or possible AE and admitted to the neurology ICU between January 2015 and December 2023. Neurological outcomes at 6 and 12 months were assessed using the modified Rankin scale (mRS). The study further analyzed the relationship between their clinical characteristics, auxiliary examinations, and prognosis. A total of 134 adult patients with AE requiring ICU admission were included. The 6- and 12-month survival rates were 91.8

Parkinson's disease (PD) is a progressive neurodegenerative disorder primarily driven by the degeneration of dopaminergic neurons, with limited therapeutic interventions currently available. Among the critical factors in PD pathogenesis, DJ-1, a multifunctional protein, has emerged as a key neuroprotective agent against oxidative stress—a major contributor to the disease. Recent research has emphasized the pivotal role of DJ-1 dimerization in enhancing its neuroprotective capabilities. This review provides an in-depth analysis of the molecular mechanisms underlying DJ-1 dimerization and its relevance to PD. Specifically, we specifically explore how dimerization stabilizes DJ-1, enhances its antioxidative properties, improves mitochondrial function, and modulates key cellular pathways essential for neuronal survival. Furthermore, we discuss the molecular determinants governing DJ-1 dimerization, highlighting its potential both as a biomarker for PD diagnosis and a promising therapeutic target. By synthesizing current advancements, we propose that targeting DJ-1 dimerization may offer innovative strategies to slow PD progression and bolster neuronal health. This review positions DJ-1 as a central focus in PD research, paving the way for future studies aimed at developing neuroprotective therapies. Neuroprotective Role of DJ-1 Dimers and Their Regulation in PD. This schematic highlights the neuroprotective role of DJ-1 dimers in PD. Post-translational modifications (PTMs) such as oxidation (O), phosphorylation (P), and S-nitrosylation (S), as well as molecular chaperones like BAG1, regulate the formation of DJ-1 dimers. DJ-1 dimerization is emphasized as a critical feature for stabilizing its structure and enhancing its neuroprotective functions, including antioxidative stress regulation (mitigating reactive oxygen species [ROS]), mitochondrial homeostasis, molecular chaperone activity, and neuronal survival. Therefore, screening for factors that regulate DJ-1 dimer formation may represent a novel therapeutic target for protecting neurons.

Background and aimsForecasting specific factors influencing cognitive impairment (CI) in Parkinson’s disease (PD) patients can improve clinical outcomes. This study aims to identify brain areas vulnerable to vitamin D deficiency and assess functional integrity in PD patients with and without CI.MethodsThirty-four PD patients [14 with CI (PD-CI), 20 with normal cognition (PD-NC)] and 21 healthy controls (HCs) underwent serum vitamin D testing, T1-weighted MRI, and resting-state functional MRI (rs-fMRI). Voxel-based morphometry (VBM) was used to compare gray matter volume (GMV) between PD patients and HCs. Whole-brain multiple regression analyses, adjusted for age and sex, identified GMV regions associated with vitamin D levels. Resting-state functional connectivity (FC) analyses were performed using vitamin D-related regions as seeds. Correlation and multivariate regression analyses, adjusted for Hoehn and Yahr stage and age, assessed relationships among FC, cognitive performance, and vitamin D levels.ResultsCompared with HCs, PD patients exhibited significant GMV loss, affecting widespread brain regions including the middle frontal gyrus (MFG), superior frontal gyrus (SFG), and hippocampus. Region of interest (ROI)-based analysis revealed that vitamin D levels were associated with GMV in the bilateral MFG and SFG (r = −0.406, p = 0.021). These findings suggest that the MFG and SFG are vulnerable regions in PD patients linked to vitamin D levels. To assess the impact of abnormal vitamin D levels on relevant resting-state networks, clusters encompassing the bilateral SFG were used as ROIs. The intrinsic connectivity network of the vulnerable area, using the bilateral SFG as seed regions, revealed abnormal functional connectivity with several brain networks, including the visual network, the default mode network, the executive control network, the sensorimotor network, and the memory network. Abnormal FC values within the SFG functional network were associated with disease severity, cognitive dysfunction, and vitamin D levels (p < 0.05). Multi-model regression analyses revealed that connectivity in the left SFGmed network was negatively associated with CI in PD, with vitamin D levels showing a potential protective effect.ConclusionThe SFG is associated with vitamin D levels in PD patients, and disruptions in its structural and functional connectivity may link to CI. Future longitudinal studies are necessary to confirm these associations and explore the potential impact of vitamin D supplementation on cognitive function in PD.

ObjectivesInfection with Carbapenem-resistant Gram-negative bacteria (CR-GNB) poses further challenges in treating stroke-associated pneumonia (SAP) patients. This multicenter retrospective study aimed to evaluate the efficacy of polymyxin B (PMB) in CR-GNB-infected SAP patients and to identify factors that may influence its effectiveness.MethodsFrom 1 September 2019, and 30 December 2022, a total of 196 CR-GNB-infected SAP patients from five hospitals in China were included in the study based on specific criteria. Demographics and clinical data were obtained from the electronic medical records. Propensity score matching (PSM) was used to minimize the effect of potential confounding variables. Univariate analysis and multivariate logistic analysis were performed to identify risk factors affecting microbial efficacy.ResultsAmong the 196 SAP patients infected with CR-GNB, 24.5% received PMB combined inhalation and 75.5% received non-combined inhalation treatment. The clinical success rate was 68.9%, with 25.5% achieving microbial efficacy within 7 days and 37.8% achieving microbial cure. The 30-day all-cause mortality rate was 14.8%. The incidence of acute kidney injury was 34.7%. After adjustment by propensity score matching, the PMB combined inhalation group exhibited significantly higher microbial efficacy compared to the non-combined inhalation group (46.7% vs. 26.7%, p = 0.049). Multivariate logistic analysis identified multi-site infections and Carbapenem-resistant Pseudomonas aeruginosa infection as independent risk factors for microbial efficacy.ConclusionCombined inhalation of PMB demonstrated superior effectiveness in microbial clearance compared to non-combined inhalation in treating CR-GNB-infected SAP patients. We recommend aerosol combined inhalation of PMB and suggest developing personalized PMB-based regimens for individual patients to enhance treatment outcomes.

INTRODUCTION:Frontotemporal dementia (FTD) is the third most frequent dementia and the leading dementia subtype in individuals under 65. The discovery of C9orf72 (chromosome 9 open reading frame 72) GGGGCC abnormal expansion is a major genetic cause of both FTD and amyotrophic lateral sclerosis (ALS), linking these diseases along a clinicopathological spectrum. This study aimed to depict the research landscape of C9orf72 in FTD over the past decade, track emerging research hotspots, and provide insights into under-researched areas. METHOD:Based on the Web of Science database, a bibliometric analysis was conducted to explore publication trends, key contributors, funding sources, journal categories, co-authorship networks, and keyword co-occurrence, clustering, and bursts. RESULTS:A total of 1,220 articles were identified, with sustained output of over 100 articles annually. The majority of contributions and funding support came from North America and Europe. Hot research themes included hexanucleotide repeats, nucleocytoplasmic transport, disease mechanisms, and therapeutic targets. DISCUSSION:North America and Europe were highly productive, supported by higher regional prevalence, genetic burden, and robust funding. Ploy-GR in cerebrospinal fluid has emerged as a diagnostic biomarker. Pathogenic mechanisms remain complex, involving both gain- and loss-of-function effects. Metformin and antisense oligonucleotides were considered as potential therapeutics. Further research is needed in underrepresented populations and on the translational potential of emerging molecular targets. CONCLUSION:This study offers a comprehensive overview of current trends and future directions over the past decade in C9orf72-related FTD research, allowing researchers-particularly those new to the area-to quickly understand the current landscape.

Background:Medication adherence in essential tremor (ET) remains poorly characterized. This real world study aimed to investigate adherence rates, clinical correlates, and predictors among ET patients in China. Methods:A prospective cohort of 318 ET patients (116 pure ET, 202 ET-plus) was followed for a mean of 22.91 ± 3.86 months. Standardized assessments included the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Non-Motor Symptoms Scale (NMSS). Adherence was defined as daily use of prescribed tremor medications. Logistic regression identified predictors. Results:Only 27.4% (87/318) maintained daily adherence. ET-plus patients showed higher adherence than pure ET (32.2% vs 19.0%, P = 0.011). Arotinolol was the most common medication. Compared to non-adherent patients, adherent patients showed higher urban residency (P = 0.026), head tremor prevalence (P = 0.002), mild cognitive impairment (P = 0.038), higher TETRAS-I (P = 0.047) and TETRAS-II scores (P = 0.008), as well as lower MoCA scores (P = 0.021). Multivariable analysis showed better medication adherence was significantly associated with higher TETRAS-II score (OR = 1.041, 95% CI = 1.001-1.082, P = 0.047), urban residence (OR = 1.775, 95% CI = 1.066-2.957, P = 0.028), and the presence of head tremor (OR = 1.936, 95% CI = 1.125-3.332, P = 0.017). No significant association was found between ET subtypes and adherence (P > 0.05). Conclusion:Medication adherence is alarmingly low in Chinese ET patients, especially in pure ET. Greater tremor severity, presence of head tremor, and urban residence were independently associated with better medication adherence. Highlight:Medication adherence among Chinese essential tremor (ET) patients remains suboptimal (only 27.4% in our cohort). ET plus patients showed higher adherence (32.2%) than pure ET (19.0%). Predictors of adherence included severe tremor (TETRAS-II), urban residence, and head tremor. Arotinolol was the predominant treatment. Findings emphasize the need for personalized interventions.

OBJECTIVES:Augmented renal clearance (ARC), in contrast to renal dysfunction, refers to enhanced renal elimination of circulating solutes compared to the expected baseline. Although patients may present with normal serum creatinine (Scr) levels, the incidence of ARC is high in intensive care unit (ICU) settings. ARC is associated with subtherapeutic exposure and treatment failure of renally cleared antibiotics. However, limited research exists on the incidence and risk factors of ARC in the ICU, and even fewer data are available specifically for neurological ICU (NICU). This study aims to determine the incidence and risk factors of ARC in neurocritically ill patients. METHODS:We retrospectively analyzed all available Scr data of neurocritical care patients admitted to the NICU of the Second Xiangya Hospital of Central South University between December 2020 and January 2023. Creatinine clearance (CrCl) was calculated using the Cockcroft-Gault equation. ARC was defined as a CrCl≥130 mL/(min·1.73 m2) sustained for more than 50% of the duration of the NICU stay. A total of 208 neurocritically ill patients were assigned into an ARC group (n=52) and a non-ARC (N-ARC) group (n=156). Clinical characteristics were compared between the 2 groups. Variables with P<0.05 in univariate analysis were included in binary Logistic regression to identify independent risk factors for ARC. RESULTS:The incidence of ARC among neurocritically ill patients was 25.00%. Of the 74 patients with normal CrCl, 20 (27.03%) gradually developed ARC during hospitalization. Compared with the N-ARC group, the patients of the ARC group were younger (P<0.001), with a higher proportion of females (P=0.048) and a lower admission mean arterial pressure (MAP) (P=0.034). Moreover, patients of the ARC group were commonly complicated with severe bacterial infections compared with the patients of the N-ARC group (P<0.001). In binary Logistic regression analysis, younger age (OR=0.903, 95% CI 0.872 to 0.935) and severe bacterial infections (OR=6.270, 95% CI 2.568 to 15.310) were significant predictors of ARC. CONCLUSIONS:ARC is relatively common in the NICU. A considerable number of patients with initially normal renal function developed ARC during hospitalization. Younger age and concurrent severe bacterial infection are important risk factors of ARC in neurocritically ill patients.

BackgroundObservational studies have shown that oxidative stress (OS) is associated with Parkinson’s disease (PD). However, whether such observations reflect cause–effect remains largely unknown. To test this, we performed a two-sample bidirectional Mendelian randomization (MR) analysis to investigate the causal-effects between OS biomarkers and PD.MethodsWe selected summary statistics data for single-nucleotide polymorphisms (SNPs) associated with catalase (n = 13), glutathione peroxidases (n = 12), superoxide dismutase (n = 13), vitamin A (n = 7), vitamin C (n = 10), vitamin E (n = 12), vitamin B12 (n = 8), folate (n = 14), copper (n = 6), Zinc (n = 7), and iron (n = 23) levels, and the corresponding data for PD from the International Parkinson Disease Genomics Consortium (IPDGC, 33,674 cases and 449,056 controls). Inverse-variance weighted (IVW) MR analyses were conducted to estimate associations of OS with PD. Reverse MR analysis was further performed to predict the causal effects of PD on the above OS biomarkers.ResultsAs for PD, the IVW method suggested that the Zinc (Zn) levels was significantly associated with PD (OR = 1.107, 95% CI 1.013–1.211; p = 0.025), which is consistent with results from the weighted median analyses. Moreover, the results remained consistent and robust in the sensitivity analysis. However, there were no significant associations of catalase, glutathione peroxidases, superoxide dismutase, vitamin A, vitamin C, vitamin E, vitamin B12, folate, copper, or iron with PD. As for OS, our reverse MR analysis also did not support a causal effect of liability to PD on OS.ConclusionThe MR study supported the causal effect of Zn on PD. These findings may inform prevention strategies and interventions directed toward OS and PD.

OBJECTIVE:To compare the differential impact of recombinant protein A immunoadsorption (PAIA) or therapeutic plasma exchange (TPE) on neurological functional improvement and quality of life in patients afflicted with severe acute neuroimmune diseases, including Guillain-Barré syndrome (GBS), myasthenia gravis (MG), neuromyelitis optica spectrum disorder (NMOSD), and anti-NMDA receptor encephalitis (NMDARE). METHODS:The retrospective study included 29 patients with moderate to severe disability (modified Rankin scale, mRS≥3) due to acute neuroimmune diseases at the second Xiangya hospital from January 2021 to January 2023. The clinical efficacy of PAIA and TPE in improving neurological function (ΔmRS≥1) and the difference in favorable functional outcomes (mRS 0-2) at three months were evaluated. The impact of both treatments on patients' health-related quality of life (HRQoL) was assessed using a visual analog scale (EQ-VAS) score ranging from 0 to 100. RESULTS:The findings revealed that the PAIA group exhibited a significantly higher rate of improvement in modified Rankin scale (mRS) scores (ΔmRS≥1) at the three-month follow-up compared to the TPE group (94.4 % vs. 54.5 %, p = 0.018). However, no statistically significant difference was observed between the two treatment modalities in terms of favorable neurological functional outcomes at the three-month mark. Furthermore, the PAIA group demonstrated a significantly higher EQ-VAS score at 14 days post-treatment compared to the TPE group (60.0 vs. 47.7, p = 0.017). CONCLUSION:In the short-term management of severe acute neuroimmune diseases, PAIA may present a greater probability of improving neurological function and facilitating an earlier enhancement of quality of life compared to TPE.

IntroductionBalamuthia amoebic encephalitis (BAE), caused by Balamuthia mandrillaris, is a rare and life-threatening infectious disease with no specific and effective treatments available. The diagnosis of BAE at an early stage is difficult because of the non-specific clinical manifestations and neuroimaging.Case descriptionA 52-year-old male patient, who had no previous history of skin lesions, presented to the emergency department with an acute headache, walking difficulties, and disturbance of consciousness. The patient underwent a series of examinations, including regular cerebrospinal fluid (CSF) studies and magnetic resonance imaging, and tuberculous meningoencephalitis was suspected. Despite being treated with anti-TB drugs, no clinical improvement was observed in the patient. Following corticosteroid therapy, the patient developed a rapid deterioration in consciousness with dilated pupils. Metagenomic next-generation sequencing (mNGS) revealed an unexpected central nervous system (CNS) amoebic infection, and the patient died soon after the confirmed diagnosis.ConclusionThis study highlights the application of mNGS for the diagnosis of patients with suspected encephalitis or meningitis, especially those caused by rare opportunistic infections.

PURPOSE:Acute necrotizing encephalopathy (ANE), a rare and severe brain disorder, is typically linked to prior infections. ANE predominantly affects children, with most reported cases attributed to viral infections. However, instances of bacterial-induced ANE are infrequent. Here, we present a case of adult-onset ANE associated with bacterial infection. CASE DESCRIPTIONS:The patient exhibited a hyperinflammatory state following a urinary tract bacterial infection, with neurological function rapidly declining into a coma as the illness progressed. Gram culture of blood suggested Escherichia coli infection. A magnetic resonance imaging (MRI) scan of the brain showed symmetrical hyperintense lesions involving bilateral thalami and pons in T2-weighted and fluid-attenuated inversion recovery images. These lesions also presented with diffuse cerebral edema and diffusion restriction and subacute hemorrhage. Based on clinical symptoms and typical brain MRI, ANE was diagnosed, and the patient underwent immunotherapy. CONCLUSIONS:This case underscores the occurrence of ANE triggered by bacterial infection, expanding our understanding of the pathogens associated with this condition. It suggests that ANE may be an immune-mediated disorder rather than solely an infectious disease.

To investigate the mechanism of Golgi matrix protein 130(GM130) regulating the antiviral immune response of TLR3 after herpes simplex virus type 1(HSV-1) infection of microglia cells. We explored the regulatory effects of berberine on the immune response mediated by GM130 and TLR3. An in vitro model of HSV-1 infection was established by infecting BV2 cells with HSV-1. Compared to the uninfected group, the Golgi apparatus (GA) fragmentation and GM130 decreased after HSV-1 infection; TLR3 increased at 6 h and began to decrease at 12 h after HSV-1 infection; the secretion of interferon-beta(IFN-β), tumour necrosis factor alpha(TNF-α), and interleukin-6(IL-6) increased after infection. Knockdown of GM130 aggravated fragmentation of the GA and caused TLR3 to further decrease, and the virus titer also increased significantly. GM130 knockdown inhibits the increase in TLR3 and inflammatory factors induced by TLR3 agonists and increases the viral titer. Overexpression of GM130 alleviated fragmentation of the GA induced by HSV-1, partially restored the levels of TLR3, and reduced viral titers. GM130 overexpression reversed the reduction in TLR3 and inflammatory cytokine levels induced by TLR3 inhibitors. Therefore, the decrease in GM130 levels caused by HSV-1 infection leads to increased viral replication by inhibiting TLR3-mediated innate immunity. Berberine can protect the GA and reverse the downregulation of GM130, as well as the downregulation of TLR3 and its downstream factors after HSV-1 infection, reducing the virus titer. In microglia, one mechanism of HSV-1 immune escape is disruption of the GM130/TLR3 pathway. Berberine protects the GA and enhances TLR3-mediated antiviral immune responses.

PURPOSE:Glial fibrillary acidic protein astrocytopathy (GFAP-A) pathogenesis remains uncertain, with potential viral involvement. More clinical cases are needed to deepen our understanding of this disease, along with the exploration of more effective treatment options to provide clinicians with additional choices. METHODS:We report a severe case of GFAP-A secondary to EBV infection, characterized predominantly by central respiratory failure. Additionally, we conducted a literature review summarizing the characteristics of GFAP-IgG-positive patients associated with EBV infection. RESULTS:Among the 13 patients identified, fever (92.3%) and headache (84.6%) were the most common initial symptoms, while urinary dysfunction was universally present in all patients. Over half of the patients with altered consciousness required endotracheal intubation (7/11, 63.6%), with only one individual experiencing complete resolution without any residual sequela. Only two patients (16.7%) displayed the classic feature of periventricular enhancement on neuroimaging, whereas T2-FLAIR hyperintensities were more prevalent. All patients tested positive for GFAP-IgG in CSF, and 91.7% (11/12) had detectable serum GFAP-IgG antibodies. Three patients (23.1%) achieved full recovery solely through antiviral therapy. In patients receiving various immunotherapies, 60% (6/10) still had residual sequelae. CONCLUSION:EBV infection may contribute to the pathogenesis of GFAP-A. GFAP antibody testing is recommended for diagnostic evaluation in cases of central nervous system viral infections presenting with respiratory insufficiency. For severe GFAP-A patients, Protein A immunoadsorption (Protein A IA).

Parkinson's disease (PD) is a common neurodegenerative disease implicated in multiple interacting neurotransmitter pathways. Glutamate is the central excitatory neurotransmitter in the brain and plays critical influence in the control of neuronal activity. Impaired Glutamate homeostasis has been shown to be closely associated with PD. Glutamate is synthesized in the cytoplasm and stored in synaptic vesicles by vesicular glutamate transporters (VGLUTs). Following its exocytotic release, Glutamate activates Glutamate receptors (GluRs) and mediates excitatory neurotransmission. While Glutamate is quickly removed by excitatory amino acid transporters (EAATs) to maintain its relatively low extracellular concentration and prevent excitotoxicity. The involvement of GluRs and EAATs in the pathophysiology of PD has been widely studied, but little is known about the role of VGLUTs in the PD. In this review, we highlight the role of VGLUTs in neurotransmitter and synaptic communication, as well as the massive alterations in Glutamate transmission and VGLUTs levels in PD. Among them, adaptive changes in the expression level and function of VGLUTs may exert a crucial role in excitatory damage in PD, and VGLUTs are considered as novel potential therapeutic targets for PD.