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Introduction: Increasing evidence suggests that air pollution has a significant impact on the development of synucleinopathies, but the potential neurobiological mechanisms are unknown. We aimed to explore the associations of air pollution (including ozone [O3], nitrogen dioxide [NO2], and particulate matter [PM2.5]) with CSF α-syn levels in urban older adults. Methods: We included 933 urban participants from the Chinese Alzheimer's Biomarker and LifestylE study. The 5-year average levels of air pollution exposure were estimated in the areas of residence. Multivariate linear regression was conducted to detect the correlation of air pollution with CSF α-syn levels. Subgroup analyses by age, gender, season, and history of coronary heart disease (CHD) were performed. Moreover, restricted cubic spline (RCS) models were applied to explore the potential nonlinear relationships. Results: We found a significant correlation of CSF α-syn level with PM2.5 in urban participants. Specifically, multiple linear regression showed a significant negative association between PM2.5 and CSF α-syn level (p = 0.029), which was more significant in female, midlife, non-CHD, and cold season subgroups. Besides, RCS models showed that O3 had an inverse J-shaped association with CSF α-syn levels in urban participants (p for nonlinearity = 0.040), and the harmful effect possibly appeared when O3 was above 37.9 ppb. Discussion: Long-term exposure to air pollution was associated with lower CSF α-syn levels, which may offer a new direction for exploring and preventing synucleinopathies. [ABSTRACT FROM AUTHOR]

Background: Spinal muscular atrophy (SMA) is a neurodegenerative disorder. Although prior studies have investigated the metabolomes of SMA in various contexts, there is a gap in research on cerebrospinal fluid (CSF) metabolomics compared to healthy controls. CSF metabolomics can provide insights into central nervous system function and patient outcomes. This study aims to investigate CSF metabolite profiles in untreated SMA patients to enhance our understanding of SMA metabolic dysregulation. Methods: This case control study included 15 SMA patients and 14 control subjects. CSF samples were collected, and untargeted metabolomics was conducted to detect metabolites in SMA and control groups. Results: A total of 118 metabolites abundance were significantly changed between the SMA and control groups. Of those, 27 metabolites with variable importance for the projection (VIP) ≥ 1.5 were identified. The top 5 differential metabolites were N-acetylneuraminic acid (VIP = 2.38, Fold change = 0.43, P = 5.49 × 10–5), 2,3-dihydroxyindole (VIP = 2.33, Fold change = 0.39, P = 1.81 × 10–4), lumichrome (VIP = 2.30, Fold change = 0.48, P = 7.90 × 10–5), arachidic acid (VIP = 2.23, Fold change = 10.79, P = 6.50 × 10–6), and 10-hydroxydecanoic acid (VIP = 2.23, Fold change = 0.60, P = 1.44 × 10–4). Cluster analysis demonstrated that the differentially metabolites predominantly clustered within two main categories: protein and amino acid metabolism, and lipid metabolism. Conclusions: The findings highlight the complexity of SMA, with widespread effects on multiple metabolic pathways, particularly in amino acid and lipid metabolism. N-acetylneuraminic acid may be a potential treatment for functional improvement in SMA. The exact mechanisms and potential therapeutic targets associated with metabolic dysregulation in SMA require further investigation. [ABSTRACT FROM AUTHOR]

Objective: The cingulate sulcus sign (CSS) has been observed in patients with idiopathic normal pressure hydrocephalus (iNPH), suggesting potential disruptions in cerebrospinal fluid circulation and compromised glymphatic system. Although there are similarities in the underlying mechanisms between cerebral small vessel disease (CSVD) and iNPH, the relationship between CSS and CSVD remains unclear. This study aimed to investigate the prevalence and potential mechanisms of CSS in patients with CSVD. Methods: Data from patients diagnosed with CSVD at Shengjing Hospital of China Medical University between January 2020 and October 2022 were retrospectively collected, including general information, global cognitive function [assessed by measuring Mini-Mental State Examination (MMSE)], and four CSVD magnetic resonance imaging (MRI) markers [(white matter hyperintensity (WMH), cerebral microbleeds (CMBs), lacunes, and enlarged perivascular spaces (EPVS)], CSS and the Evan's index (EI). Results: A total of 308 patients were included, and CSS was detected in 80 patients (26%). Univariate analysis revealed that MMSE scores in the CSS group were significantly lower compared to the non-CSS group (p < 0.001). Multivariable analysis showed an independent correlation between CSS and the presence of lacunes (odds ratio [OR] 0.358, 95% confidence interval [CI] 0.193-0.663, p = 0.001), presence of lobar dominant CMBs (OR 2.683, 95%CI 1.385-5.195, p = 0.003), periventricular WMH Fazekas score (OR 1.693, 95% CI 1.133-2.529, p = 0.01), and EI (OR 1.276, 95% CI 1.146-1.420, p < 0.001). Conclusion: This preliminary study showed that CSS can be observed in some patients with CSVD. The presence of CSS may represent different mechanisms of CSVD pathogenesis and reflect differences in the degree of cerebrospinal fluid (CSF)/interstitial fluid (ISF) stasis. [ABSTRACT FROM AUTHOR]

Background: Shunt obstruction is a type of ventriculoperitoneal shunt (VPS) failure. Whether changes in cerebrospinal fluid (CSF) parameters can influence shunt outcomes or not is debatable. Methods: In this study, we retrospectively included adult hydrocephalus patients who received VPS from 6 general hospitals in different provinces of China from November 2013 to September 2021. The inclusion criteria: Patients with hydrocephalus of all etiologies underwent shunt surgery from 6 general hospitals in different provinces of China were included in the study. The exclusion criteria: 1.Patients under the age of 18; 2.Patients who had previous shunt surgery; 3. Shunt failure from other factors; 4.Patients died from other causes; 5. Patients with incomplete data. The CSF of shunt patients had been analyzed at the time of shunt insertion. The CSF samples were collected and analyzed when the shunt was implanted. The relationship between CSF parameters and the incidence rate of shunt obstruction in one year was analyzed. Results: A total of 717 eligible patients from 6 hospitals were included, of whom 59(8.23%) experienced obstruction. Multivariate logistic regression analysis identified that protein level(odds ratio [OR] 1.161, 95% CI 1.005 ~ 1.341, p = 0.043), decreased glucose level(< 2.5 mmol/L)(odds ratio 3.784, 95% confidence interval 1.872 ~ 7.652, p = 0.001) and protein level increase(> 0.45 g/L) (odds ratio 3.653, 95% confidence interval 1.931 ~ 6.910, p = 0.001)were independent risk factors of shunt obstruction. Conclusion: This study suggested that increased protein level (> 0.45 g/L) and decreased glucose level (< 2.5 mmol/L) in CSF indicated an increased risk of shunt obstruction in a patient with hydrocephalus. Thus, shunt surgery should be more carefully considered when the CSF glucose and protein were abnormal. [ABSTRACT FROM AUTHOR]

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) and can be difficult to diagnose and treat. We aimed to describe the clinical presentation, diagnosis, disease spectrum, outcome, and prognostic factors of patients treated for TBM in China. Methods: A multicenter retrospective study was conducted from 2009 to 2019 enrolling all presumptive TBM patients referred to Xijing tertiary Hospital from 27 referral centers in and around Shaanxi province, China. Patients with clinical features suggestive of TBM (abnormal CSF parameters) were included in the study if they had adequate baseline information to be classified as "confirmed," "probable," or "possible" TBM according to international consensus TBM criteria and remained in follow-up. Patients with a confirmed alternative diagnosis or severe immune compromise were excluded. Clinical presentation, central nervous system imaging, cerebrospinal fluid (CSF) results, TBM score, and outcome--assessed using the modified Barthel disability index--were recorded and compared. Findings: A total of 341 presumptive TBM patients met selection criteria; 63 confirmed TBM (25 culture positive, 42 Xpert-MTB/RIF positive), 66 probable TBM, 163 possible TBM, and 49 "not TBM." Death was associated with BMRC grade III (OR = 5.172; 95%CI: 2.298-11.641), TBM score = 15 (OR = 3.843; 95%CI: 1.372-10.761), age > 60 years (OR = 3.566; 95%CI: 1.022-12.442), and CSF neutrophil ratio = 25% (OR = 2.298; 95%CI: 1.027-5.139). Among those with confirmed TBM, nearly one-third (17/63, 27.0%) had a TBM score < 12; these patients exhibited less classic meningitis symptoms and signs and had better outcomes compared with those with a TBM score = 12. In this group, signs of disseminated/miliary TB (OR = 12.427; 95%CI: 1.138-135.758) and a higher TBM score (=15, OR = 8.437; 95%CI: 1.328-53.585) were most strongly associated with death. Conclusion: TBM patients who are older (>60 years) have higher TBM scores or CSF neutrophil ratios, have signs of disseminated/miliary TB, and are at greatest risk of death. In general, more effort needs to be done to improve early diagnosis and treatment outcome in TBM patients. [ABSTRACT FROM AUTHOR]

Objective To report and analyze the clinical features of the first documented case in China of anti-neurofilament heavy chain (NfH) antibody-associated encephalitis. Methods and Results A 63-year-old female presented with cognitive impairment, recurrent epileptic episodes, and aphasia. Head MRI showed multiple abnormal signals in bilateral frontal and parietal lobes, and slight swelling in some gyri, dilatation of the supratentorial ventricular system and brain atrophy, especially in bilateral temporal lobes and hippocampus. 18F-DPA714 PET/MRI showed abnormal uptake in multiple brain regions in the frontal, temporal, parietal and occipital lobes, suggesting neuroinflammation in the brain. EEG showed frequent epileptiform discharges. Cerebrospinal fluid white cell count and glucose were elevated. Serum and cerebrospinal fluid antibodies related to autoimmune encephalitis were negative. Serum tissue-based indirect immunofluorescence assay showed cerebellar neurofilament-like fluorescence surrounding Purkinje cells, further detection of neurofilament protein-related antibodies, it suggested high titer of serum NfH-IgG (1:1000). The patient was diagnosed with anti-NfH antibody-associated encephalitis. After treatment with intravenous immunoglobulin and methylprednisolone, the prognosis was improved. Conclusions Anti-NfH antibody-associated encephalitis is a rare and clinically complex condition. The myriad of symptoms complicates early diagnosis and differential identification. Early initiation of immunomodulatory therapy may offer prognostic advantages. [ABSTRACT FROM AUTHOR]

Introduction: Novelty detection (ND, also known as one-class classification) is a machine learning technique used to identify patterns that are typical of the majority class and can discriminate deviations as novelties. In the context of Alzheimer's disease (AD), ND could be employed to detect abnormal or atypical behavior thatmay indicate early signs of cognitive decline or the presence of the disease. To date, few research studies have used ND to discriminate the risk of developing AD and mild cognitive impairment (MCI) from healthy controls (HC). Methods: In this work, two distinct cohorts with highly heterogeneous data, derived from the Australian Imaging Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing project and the Fujian Medical University Union Hospital (FMUUH) China, were employed. An innovative framework with built-in easily interpretable ND models constructed solely on HC data was introduced along with proposing a strategy of distance to boundary (DtB) to detect MCI and AD. Subsequently, a web-based graphical user interface (GUI) that incorporates the proposed framework was developed for non-technical stakeholders. Results: Our experimental results indicate that the best overall performance of detecting AD individuals in AIBL and FMUUH datasets was obtained by using the Mixture of Gaussian-based ND algorithmapplied to singlemodality, with an AUC of 0.8757 and 0.9443, a sensitivity of 96.79% and 89.09%, and a specificity of 89.63% and 90.92%, respectively. Discussion: The GUI offers an interactive platform to aid stakeholders in making diagnoses of MCI and AD, enabling streamlined decision-making processes. More importantly, the proposed DtB strategy could visually and quantitatively identify individuals at risk of developing AD. [ABSTRACT FROM AUTHOR]

Background: Breast cancer has the highest incidence rate of cancer worldwide, and brain metastases (BrM) are among the most malignant cases. While some patients have benefited from immune checkpoint inhibitors (ICIs), the complex anatomical structure of the brain and the heterogeneity of metastatic tumors have made it difficult to characterize the tumor immune microenvironment (TME) of metastatic tumors. Methods: To address this, we used single‐cell RNA sequencing (scRNA‐seq) to analyze immune cells in the cerebrospinal fluid (CSF) of BrM patients with breast cancer, thereby providing a comprehensive view of the immune microenvironment landscape of BrM. Results: Based on canonical marker genes, we identified nine cell types, and further identified their subtypes through differential expression gene (DEG) analysis. We compared the changes in cells and functions in the immune microenvironment of patients with different prognoses. Our analysis revealed a series of genes that promote tumor immune function (CCR5, LYZ, IGKC, MS4A1, etc.) and inhibit tumor immune function (SCGB2A2, CD24, etc.). Conclusions: The scRNA‐seq in CSF provides a noninvasive method to describe the TME of breast cancer patients and guide immunotherapy. [ABSTRACT FROM AUTHOR]

Bitespiramycin, has been shown to have a therapeutic effect against respiratory tract inflammation, including a potential effect against COVID-19. A current clinical trial in China showed that bitespiramycin was an effective treatment for severe pneumonia and intracranial infection. However, there is lack of an analytical method to elucidate the distribution of bitespiramycin. In this study, a highly sensitive, rapid and reliable UPLC–MS/MS method was developed to comprehensively characterize the bitespiramycin distribution in various bio-samples, which is significantly improved upon the published work. A rapid sample preparation method was developed by using n-butanol as the solvent to extract bitespiramycin from different bio-samples. The extract was then directly analyzed by UPLC–MS/MS coupled with an alkaline-resistant column after centrifugation which avoids the time-consuming concentration process under nitrogen and redissolution. The method was employed to accurately quantify bitespiramycin and its metabolites in rat plasma, tissues, and human cerebrospinal fluid. Notably, the presence of bitespiramycin and its metabolites was identified for the first time in various rat organs including brain, testis, bladder and prostate as well as in human cerebrospinal fluid. This newly developed approach shows great promise for drug distribution assays including other antibiotics and can help elucidate the ADME of bitespiramycin. [ABSTRACT FROM AUTHOR]

Background: Cerebrospinal fluid oligoclonal band (CSF-OCB) is an established biomarker in diagnosing multiple sclerosis (MS), however, there are no nationwide data on CSF-OCB prevalence and its diagnostic performance in Chinese MS patients, especially in the virtue of common standard operation procedure (SOP). Methods: With a consensus SOP and the same isoelectric focusing system, we conducted a nationwide multi-center study on OCB status in consecutively, and recruited 483 MS patients and 880 non-MS patients, including neuroinflammatory diseases (NID, n = 595) and non-inflammatory neurological diseases (NIND, n=285). Using a standardized case report form (CRF) to collect the clinical, radiological, immunological, and CSF data, we explored the association of CSF-OCB positivity with patient characters and the diagnostic performance of CSF-OCB in Chinese MS patients. Prospective source data collection, and retrospective data acquisition and statistical data analysis were used. Findings: 369 (76.4%) MS patients were OCB-positive, while 109 NID patients (18.3%) and 6 NIND patients (2.1%) were OCB-positive, respectively. Time from symptom onset to diagnosis was significantly shorter in OCB-positive than that in OCB-negative MS patients (13.2 vs 23.7 months, P=0.020). The prevalence of CSF-OCB in Chinese MS patients was significantly higher in high-latitude regions (41°-50°N)(P=0.016), and at high altitudes (>1000m)(P=0.025). The diagnostic performance of CSF-OCB differentiating MS from non-MS patients yielded a sensitivity of 76%, a specificity of 87%. Interpretation: The nationwide prevalence of CSF-OCB was 76.4% in Chinese MS patients, and demonstrated a good diagnostic performance in differentiating MS from other CNS diseases. The CSF-OCB prevalence showed a correlation with high latitude and altitude in Chinese MS patients. [ABSTRACT FROM AUTHOR]

Background: Clusterin, a glycoprotein implicated in Alzheimer's disease (AD), remains unclear. The objective of this study was to analyze the effect of cerebrospinal fluid (CSF) clusterin in relation to AD biomarkers using a longitudinal cohort of non-demented individuals. Methods: We gathered a sample comprising 86 individuals under cognition normal (CN) and 134 patients diagnosed with MCI via the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. To investigate the correlation of CSF clusterin with cognitive function and markers of key physiological changes, we employed multiple linear regression and mixed-effect models. We undertook a causal mediation analysis to inspect the mediating influence of CSF clusterin on cognitive abilities. Results: Pathological characteristics associated with baseline Aß42, Tau, brain volume, exhibited a correlation with initial CSF clusterin in the general population, Specifically, these correlations were especially prominent in the MCI population; CSF Aß42 (PCN = 0.001; PMCI = 0.007), T-tau (PCN < 0.001; PMCI < 0.001), and Mid temporal (PCN = 0.033; PMCI = 0.005). Baseline CSF clusterin level was predictive of measurable cognitive shifts in the MCI population, as indicated by MMSE (ß = 0.202, p = 0.029), MEM (ß = 0.186, p = 0.036), RAVLT immediate recall (ß = 0.182, p = 0.038), and EF scores (ß = 0.221, p = 0.013). In MCI population, the alterations in brain regions (17.87% of the total effect) mediated the effect of clusterin on cognition. It was found that variables such as age, gender, and presence of APOE e4 carrier status, influenced some of these connections. Conclusion: Our investigation underscored a correlation between CSF clusterin concentrations and pivotal AD indicators, while also highlighting clusterin's potential role as a protective factor for cognitive abilities in MCI patients. [ABSTRACT FROM AUTHOR]

Background: Isolated Prevotella intermedia, a rare gram-negative, rod-shaped, anaerobic bacterium, is rarely detected in clinical practice. It has been associated with infections of the oral cavity and female genital tract, but has never been detected in cerebrospinal fluid (CSF) of patients in China. Accurate detection of causative pathogens is still an arduous task owing to the difficult conditions of anaerobic bacterial culture. Isolated Prevotella intermedia can be detected by metagenomic next generation sequencing (mNGS) of the CSF. Correct diagnosis and antibiotic treatment can help patients avoid life-threatening events. Case presentation: Herein, we describe the case of a 64-year-old Chinese woman who presented with typical features of meningoencephalitis. Routine CSF culture failed to identify the causative pathogen. Isolated Prevotella intermedia was detected by mNGS, and the patient was treated with antibacterial agents including ceftriaxone, vancomycin, moxifloxacin, meropenem, metronidazole, and linezolid. The patient underwent surgical treatment for abscess of left frontal parietal lobe, which was observed on magnetic resonance imaging (MRI) and was suspected to be caused by Prevotella intermedia. It was further confirmed that it was a secondary infection from the oral cavity, and the possible etiology might have been dental surgery. Treatment was rendered to the patient based on metagenomic test result, and her condition improved after two months. Conclusions: This case highlights the role of mNGS in accurate diagnosis of patients with central nervous system infection. In particular, mNGS can be used to identify rare pathogens and confirm the diagnosis in patients with unknown etiology. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often absent or at low levels in the cerebrospinal fluid (CSF) of patients with previous SARS-CoV-2-associated Guillain-Barré syndrome (GBS). This has led to speculation that SARS-CoV-2-associated GBS is more likely mediated by post-infectious immunity or a parainfection. This understanding has influenced the development of treatment regimens for SARS-CoV-2-associated GBS. This paper reports our experience with four Chinese patients with SARS-CoV-2-associated GBS who tested positive for SARS-CoV-2 RNA in the CSF. They developed symptoms of peripheral nerve damage 4–15 days after fever and confirmed SARS-CoV-2 infection, all of whom presented with progressive weakness of both lower limbs; three with autonomic nerve function impairment such as constipation and urination disorder; and one with polycranial neuritis and Miller–Fisher syndrome. Three patients were tested for anti-ganglioside antibodies, and one tested positive for GD1a-IgG. Four patients recovered well after treatment with anti-viral drugs combined with intravenous immunoglobulin. The present results showed that SARS-CoV-2 RNA can be detected via mNGS in the CSF of some patients with SARS-CoV-2-associated GBS, suggesting that SARS-CoV-2-associated GBS may have multiple pathogeneses. [ABSTRACT FROM AUTHOR]

AQP4-IgG has been considered as the pathogenic factor leading to NMOSD. However, about 20–30% of patients lack AQP4-IgG. So far, all therapeutic medicines are ineffective for NMOSD patients without AQP4 IgG. Thus AQP4-IgG is the pathogenic factor of NMOSD has been suspected and challenged. In addition, lack of efficacy of immunotherapy in NMOSD without AQP4 IgG has been a serious problem in the neurology. Identifying the clinical and laboratory characteristics and diversities between NMOSD patients with and without AQP4-IgG can be helpful to further explore the pathogenesis of NMOSD and guide clinical treatment. This is a single-centre retrospective study in The First Hospital of Jilin University, China including 92 patients diagnosed as NMOSD from January 2013 to January 2015. The characteristics of clinic, blood, cerebrospinal fluid (CSF), and image between AQP4-IgG negative (AQP4-IgG−) and AQP4-IgG positive (AQP4-IgG+) NMOSDs were compared. Our results showed that in the AQP4-IgG+ group, the ratio of women to men was 5.55, while in AQP4-IgG− group was 1.54 (P = 0.0092). In the AQP4-IgG+ patients, the expanded disability status scale (EDSS) was from 0 to 8.5, with an average of 5.550 ± 0.25, and the AQP4-IgG− patients had the EDSS score from 0 to 9, with an average of 4.032 ± 0.36 (P = 0.0006), which mainly affected movement system (P < 0.05) and superficial sensory impairment (P < 0.05). In the AQP4-IgG+ group, the blood brain barrier (BBB) permeability (P = 0.0210) and myelin basic protein (MBP) were increased (P = 0.0310) when compared to AQP4-IgG− group. Higher level IL-17 was seen in AQP4-IgG+ group than AQP4-IgG− group (P= 0.0066). Our results demonstrated that the NMOSD with AQP4-IgG more likely occurred in women and presented more severe clinical symptoms as well as significant BBB damage and increased MBP and IL-17 in CSF and blood, respectively compared with NMOSD without AQP4-IgG group. The differences in clinical and laboratory profiles between NMOSD with and without AQP4-IgG indicate the heterogeneity of NMOSD, in which AQP4-IgG may not be the only pathogenic molecule. It is necessary to find more pathogenic factors and to explore the new pathogenesis of NMOSD and therapeutic methods in the future. In this manuscript, we identified the clinical and laboratory characteristics and diversities between NMOSD patients with and without AQP4-IgG. Our results demonstrated that the NMOSD with AQP4-IgG more likely occurred in women and presented more severe clinical symptoms as well as significant BBB damage and increased MBP and IL-17 in CSF and blood, respectively compared with NMOSD without AQP4-IgG group. [ABSTRACT FROM AUTHOR]

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Objective To investigate the influencing factors related to long - term prognosis in patients with severe tuberculous meningitis (TBM). Methods One hundred sixty-three patients with severe TBM admitted to Tianjin Haihe Hospital from June 2012 to December 2019 were included. After one year of anti-tuberculous therapy, the prognosis of the patients was evaluated by modified Rankin Scale (mRS). Univariate and multivariate stepwise Logistic regression analyses were used to analyze the influencing factors of long - term dismal prognosis of severe TBM. The predictive value was evaluated by receiver operating characteristic (ROC) curve. Results In the dismal prognosis group (mRS > 2, n = 68), patients' age (t = - 5.884, P = 0.000), hypertension (χ² = 15.769, P = 0.000), coronary heart disease (adjusted χ² = 6.785, P = 0.009), limb weakness (χ² = 9.544, P = 0.002), hydrocephalus (χ² = 23.004, P = 0.000), cerebral infarction (χ² = 17.417, P = 0.000), cerebrospinal fluid (CBF) lactic acid level (Z = - 2.405, P = 0.016) were higher than those in favourable prognosis group (mRS ≤ 2, n = 95), while Glasgow Coma Scale (GCS) score on admission was lower than that in favourable prognosis group (Z = - 6.750, P = 0.000). Logistic regression showed that old age (OR = 1.064, 95%CI: 1.031-1.098; P = 0.000) and high CSF lactic acid level (OR = 1.404, 95%CI: 1.065-1.852; P = 0.016) were risk factors for long-term dismal prognosis of severe TBM, and high GCS score on admission was a protective factor for long-term favourable prognosis of severe TBM (OR = 0.539, 95%CI: 0.405-0.716; P = 0.000). ROC curve showed the cut - off value of age for predicting long - term dismal prognosis of severe TBM on admission was 48.50 years, the area under the curve (AUC) was 0.743 (95%CI: 0.665-0.822, P = 0.000), the sensitivity was 63.20% and the specificity was 76.80%. The cut-off value of GCS score was 12.50, the AUC was 0.802 (95%CI: 0.732-0.871, P = 0.000), the sensitivity was 58.80% and the specificity was 86.30%. The cut-off value of lactic acid level in CSF was 6.99 mmol/L, the AUC was 0.611 (95%CI: 0.517-0.704, P = 0.016), the sensitivity was 42.60% and the specificity was 91.60%. The AUC of the combined application of the 3 indexes was 0.892 (95%CI: 0.841-0.944, P = 0.000), the sensitivity was 80.90% and the specificity was 88.40%, which showed that the prediction efficiency was better than that of a single index. Conclusions Advanced age and high lactic acid level in CBF are risk factors for dismal long-term prognosis of severe TBM. High GCS score on admission is a protective factor. Clinicians should focus on these factors to improve the prognosis of patients. [ABSTRACT FROM AUTHOR]

Objective • This retrospective case-control study aimed to investigate the relationship between cerebrospinal fluid (CSF) biomarkers and subarachnoid hemorrhage (SAH) and cerebral hemorrhage (CH) and to determine whether these biomarkers can predict the risk of hemorrhage. Methods • Patients diagnosed with SAH and CH at Chongqing University Central Hospital between January 2020 and April 2022 were included in this study. CSF-adenosine deaminase (ADA), CSF-lactate (Lac), and CSF-lactate dehydrogenase (LDH) were measured, and their associations with hemorrhage risk were analyzed using multivariable logistic regression models. The predictive value of these biomarkers was evaluated using receiver operating characteristic (ROC) analysis. Results • A total of 114 SAH patients, 105 CH patients, and 53 healthy controls were included in this study. The multivariable analysis revealed that hypertension, CSFADA, and CSF-Lac were independent risk factors for SAH, while hypertension and CSF-LDH were independent risk factors for CH. The ROC analysis demonstrated that the combination of CSF-ADA and CSF-Lac had the highest predictive value for SAH (area under the curve = 0.938), while CSF-LDH had the highest predictive value for CH (area under the curve = 0.946). Conclusion • CSF biomarkers, specifically CSF-ADA, CSF-Lac, and CSF-LDH, are valuable predictors of SAH and CH. These biomarkers may assist in diagnosing and managing hemorrhagic stroke in clinical settings. [ABSTRACT FROM AUTHOR]

Angiostrongylus cantonensis is the main causative agent for eosinophilic meningoencephalitis in humans. Larvae are rarely found in the cerebral spinal fluid (CSF). Consequently, serology and DNA detection represent important diagnostic tools. However, interpretation of the results obtained from these tools requires that more extensive accuracy studies be conducted. The aim of the present study is to update guidelines for diagnosis and case definitions of neuroangiostrongyliasis (NA) as provided by a working group of a recently established International Network on Angiostrongyliasis. A literature review, a discussion regarding criteria and diagnostic categories, recommendations issued by health authorities in China and an expert panel in Hawaii (USA), and the experience of Thailand were considered. Classification of NA cases and corresponding criteria are proposed as follows: minor (exposure history, positive serology, and blood eosinophilia); major (headache or other neurological signs or symptoms, CSF eosinophilia); and confirmatory (parasite detection in tissues, ocular chambers, or CSF, or DNA detection by PCR and sequencing). In addition, diagnostic categories or suspected, probable, and confirmatory are proposed. Updated guidelines should improve clinical study design, epidemiological surveillance, and the proper characterization of biological samples. Moreover, the latter will further facilitate accuracy studies of diagnostic tools for NA to provide better detection and treatment. [ABSTRACT FROM AUTHOR]

Background: Enterovirus (EV) infections are being increasingly seen in younger infants, often being more severe than in older children. The risk factors of EV infection in infants have been inadequately investigated till date. Methods: We conducted a retrospective study on hospitalized children with laboratory-confirmed EV infection (50 infants aged 0–3 months and 65 older than 3 months) at a tertiary care center in China. Prevalence, clinical characteristics, and genetic features of the virus were analyzed, and independent predictors for severe infection were assessed. Results: Clinical findings showed that severe infection was more common in infants aged 0–3 months than in older children (78.0% vs. 35.4%, p < 0.001), with higher morbidity of pneumonia, meningitis, and sepsis (p < 0.01). EV-B types were detected more frequently in infants aged 0–3 months than in older children (88.0% vs. 7.7%, p < 0.001). Echovirus 11 was the most identified EV-B, and it recombined with E6 in P2 and P3 regions. Risk factors for severe EV infection included EV-B types infection, age less than 3 months, elevated alanine aminotransferase level, abnormal platelet count, and abnormal cerebrospinal fluid characteristics. Conclusions: Our data indicated that EV-B types mainly cause severe infection in infants aged 0–3 months. Therefore, knowledge about EV-B types could have implications in designing effective intervention and prevention strategies for young infants with severe EV infection. [ABSTRACT FROM AUTHOR]

Objectives. Primary central nervous system lymphoma (PCNSL) usually has a poor prognosis. Cerebrospinal fluid (CSF) interleukin (IL)-10 has shown diagnostic, prognostic, and monitoring value in our previous studies. Cell-free circulating tumor DNA can be detected in the CSF of refractory/relapse cases and has also shown monitoring value. However, information about its monitoring value in newly diagnosed PCNSL patients and comparisons of CSF IL-10 and CSF cell-free DNA (cfDNA) are scarce. Methods. We performed next-generation sequencing on paraffin-embedded tissue and the serial CSF cfDNA of 10 newly diagnosed PCNSL patients and on the baseline CSF cfDNA of 11 other central nervous system lymphoma patients. We also monitored the CSF IL-10 levels of the 10 newly diagnosed PCNSL patients. Results. In seven newly diagnosed PCNSL patients with sufficient baseline CSF cfDNA, six had ≥1 mutated genes in their CSF cfDNA. The most common were MYD88(4/7), PIM1(3/7), MLL2(3/7), and ETV6(2/7). We also identified multiple somatic mutations, most commonly in PIM1. MYD88L265P can be detected in both tumor tissue and CSF cfDNA. The genomic profiles of CFS cfDNA were similar in PCNSL and PIOL patients. Newly diagnosed PCNSL patients with persistently positive cfDNA and negative IL-10 progressed quickly, while those with negative cfDNA and negative IL-10 were in maintenance therapy for more than 18 months. Two patients without cfDNA had increased CSF IL-10 concentrations before disease relapse. These results indicate that negative CSF cfDNA predicts better results, and persistently positive CSF cfDNA predicts disease progression earlier than conventional magnetic resonance imaging. Conclusion. In conclusion, CSF cfDNA is a potential predictor of relapse and progression, which complements the monitoring value of CSF IL-10 in newly diagnosed PCNSL patients. [ABSTRACT FROM AUTHOR]

Background: Compared with traditional diagnostic methods (TDMs), rapid diagnostic methods for infectious diseases (IDs) are urgently needed. Metagenomic next-generation sequencing (mNGS) has emerged as a promising diagnostic technology for clinical infections. Methods: This retrospective observational study was performed at a tertiary hospital in China between May 2019 and August 2022. The chi-square test was used to compare the sensitivity and specificity of mNGS and TDMs. We also performed a subgroup analysis of the different pathogens and samples. Results: A total of 435 patients with clinical suspicion of infection were enrolled and 372 (85.5%) patients were finally categorized as the ID group. The overall sensitivity of mNGS was significantly higher than that of the TDMs (59.7% vs. 30.1%, P < 0.05). However, there was no significant difference in the overall specificity between the two methods (83.3% vs. 89.6%, P = 0.37). In patients with identified pathogens, the positive rates of mNGS for detecting bacteria (88.7%), fungi (87.9%), viruses (96.9%), and Nontuberculous mycobacteria (NTM; 100%) were significantly higher than those of TDMs (P < 0.05). The positive rate of mNGS for detecting Mycobacterium tuberculosis was not superior to that of TDMs (77.3% vs. 54.5%, P = 0.11). The sensitivity rates of mNGS for pathogen identification in bronchoalveolar lavage fluid, blood, cerebrospinal fluid, pleural fluid, and tissue were 72.6%, 39.3%, 37.5%, 35.0% and 80.0%, respectively. Conclusion: With the potential for screening multiple clinical samples, mNGS has an overall advantage over TDMs. It can effectively identify pathogens, especially those that are difficult to identify using TDMs, such as NTM, chlamydia, and parasites. [ABSTRACT FROM AUTHOR]

BACKGROUND. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) plays an important role in the clearance of pathological amyloid-ß (Aß) in Alzheimer's disease (AD). This study aimed to explore sTREM2 as a central and peripheral predictor of the conversion from mild cognitive impairment (MCI) to AD. METHODS. sTREM2 and Aß1-42 levels in cerebrospinal fluid (CSF) and florbetapir-PET (AV45) images were analyzed for healthy control (HCs), patients with MCI, and patients with AD from the ADNI database. Peripheral plasma sTREM2 and Aß1-42 levels were determined for our Neurology database of Ruijin Hospital for Alzheimer's Disease (NRHAD) cohort, and patients with MCI were reevaluated at follow-up visits to assess for progression to AD. The association between CSF and plasma sTREM2 levels was analyzed in data from the Chinese Alzheimer's Biomarker and Lifestyle (CABLE) database. RESULTS. The results showed that patients with MCI who had low levels of CSF sTREM2 and Aß1-42 were more likely to develop AD. Among participants with positive Aß deposition, as assessed by AV45 imaging, elevated CSF sTREM2 levels were associated with a decreased risk of MCI-to-AD conversion. Meanwhile, in the NRHAD cohort, individuals in the MCI group with high sTREM2 levels in plasma were at a greater risk for AD, whereas low Aß1-42 with high sTREM2 levels in plasma were associated with a faster cognitive decline. In addition, CSF sTREM2 levels were highly correlated with plasma sTREM2 levels in the CABLE database. CONCLUSION. These findings suggest that sTREM2 may be useful as a potential predictive biomarker of MCI-to-AD conversion. FUNDING. This study was supported by grants from the National Natural Science Foundation of China (grant nos. 82001341, 82071415, 81873778, and 82201392); the Shanghai Sailing Program (grant no. 22YF1425100); and the China Postdoctoral Science Foundation funded project (grant no. 2021M702169). [ABSTRACT FROM AUTHOR]

Background: Research is increasingly identifying an overlap between psychosis and immunological dysregulation. Certain autoantibodies are being identified in a small but probably relevant subgroup of patients with psychosis. The term "autoimmune psychosis" (AIP) and its corresponding red-flag signs present the opportunity for a new field in psychiatry to promote diagnostic workup and immunomodulating therapy in individual cases. Objectives: The present protocol aims to determine the seroprevalence of autoantibodies in first-episode psychosis (FEPs) using AIP red flag signs, and to explore the frequency of autoantibody subtypes and potential mediating confounders. Methods/design: This is a hospital-based case-control study. All participants will be consecutively selected from the main tertiary psychiatric hospital in Shenzhen City, China. Individuals admitted to the psychiatric ward and diagnosed with FEPs will be enrolled. Based on recent consensus, participants with red flags of AIPs will be defined as cases, while the remainder will be matched as controls. Seropositive antibodies will be detected and verified in cerebrospinal fluid (CSF) samples based on the fixed cell-based assay (CBA) method. The propensity score-adjusted odds ratios will be determined to investigate the key mediating confounders regarding autoantibody subtypes and red flag subsets. Discussion: The results of this study will facilitate the early identification of AIPs in FEP patients using the red flag sign and help identify key mediators that improve the accuracy of diagnostic algorithms. It will have clinical significance to focus on serum antibodies that have been verified in CSF samples, due to its consistency with clinical practices in current psychiatry. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 is a new virus that emerged in China in December 2019, rapidly becoming a global pandemic. We report here the case of a 23-year-old man presenting with an acute dry cough associated with neurological disorders in a feverish setting. One day after being admitted to hospital, the patient presented with vertigo and asthenia. His neurological examination showed difficult standing with cerebellar walking and dysmetria. Brain MRI as well as cytochemical examination of the CSF showed normal results. The detection of SARS-CoV-2 by PCR was positive at the nasopharyngeal level and negative at the level of the CSF. The patient was treated with hydroxychloroquine, azithromycin and methylprednisolone. A good improvement was noted during his hospitalization. The cerebellar neurological involvement associated with SARS-CoV-2 was retained given the clinical and epidemiological context and taking into consideration the mechanism of neurological involvement in COVID-19 which can be direct or indirect. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study is to compare the epidemiologic, clinical, laboratory, and imaging features, and outcomes in patients with Cryptococcus gattii meningitis (CGM) and Cryptococcus neoformans meningitis (CNM). Methods: We performed a retrospective study of HIV‐negative patients with CGM and CNM (2015–2021) distinguished by metagenomic next‐generation sequencing in cerebrospinal fluid in South China. Results: A total of 81 patients (17 CGM, 64 CNM) were enrolled (72.8% male, median age 49 years, range 21–77 years), and CGM patients were younger (median, 43 vs 53 years, p =.005). Of 17 CGM, VGI and VGII accounted for 70.6% and 29.4%, respectively. CGM patients had less underlying diseases (7/17 [41.2%] vs 48/64 [75%], p =.018) and focal neurologic deficit (3/17 [17.6%] vs 35/64 [54.7%], p =.022), had higher intracranial pressure (15/17 [88.2%] vs 25/64 [39.1%], p =.002), more meningeal enhancement (14/17 [82.4%] vs 32/64 [50%], p =.034), less parenchymal involvement (median, 1 vs 3, p =.018), more lung cryptococcomas (6/12 [50%] vs 6/47 [12.8%], p =.014), faster CSF fungal clearance (p =.004), less complications (median, 1 vs 3, p <.001), and more favourable outcomes (16/17 [94.1%] vs 41/64 [64.1%], p =.035). Conclusions: This study demonstrated that species identification helps to guide therapy and predict outcomes. [ABSTRACT FROM AUTHOR]

Metagenomic next-generation sequencing (mNGS) is useful for difficult to cultivate pathogens. Here, we use cerebrospinal fluid mNGS to diagnose invasive meningococcal disease. The complete genome sequences of Neisseria meningitidis were assembled using N. meningitidis of ST4821-serotype C isolated from four patients. To investigate the phylogeny, 165 CC4821 N. meningitidis genomes from 1972 to 2017 were also included. The core genome accumulated variation at a rate of 4.84×10−8 substitutions/nucleotide site/year. CC4821 differentiated into four sub-lineages during evolution (A, B, C, and D). While evolving from sub-lineage A (early stage) to sub-lineage D (late stage), the ST and CC4821 serotype converged into the ST4821-serotype C clone. Most strains of sub-lineage D were isolated from invasive meningococcal disease, with increasing resistance to quinolones. Phylogeographic analysis suggests that CC4821 has spread across 14 countries. Thus, the selective pressure of quinolones may cause CC4821 to converge evolutionarily, making it more invasive and facilitating its spread. Metagenomic data from cerebrospinal fluid was used to genotype Neisseria meningitidis in patients with invasive meningococcal disease and trace the origin of the pathobiont, providing a phylogeographic analysis of the strain's evolution in China and its global spread. [ABSTRACT FROM AUTHOR]

Background: Information on the clinical characteristics and severity of autoimmune encephalitis with antibodies against the Nmethyl-D-aspartate receptor (NMDAR) in children is attracting more and more attention in the field of pediatric research. Methods: In this retrospective cohort study, all cases (n=67) were enrolled from a tertiary children's hospital, from 2017 to 2020. We compared severe cases that received intensive care unit (ICU) care with nonsevere cases that did not receive ICU care and used machine learning algorithm to predict the severity of children, as well as using immunologic and viral nucleic acid tests to identify possible pathogenic triggers. Results: Mean age of children was 8.29 (standard deviation 4.09) years, and 41 (61.19%) were girls. Eleven (16.42%) were admitted to the ICU, and 56 (83.58%) were admitted to neurology ward. Ten individual parameters were statistically significant differences between severe cases and nonsevere cases (P < .05), including headache, abnormal mental behavior or cognitive impairment, seizures, concomitant tumors, sputum/blood pathogens, blood globulin, blood urea nitrogen, blood immunoglobulin G, blood immunoglobulin M, and number of polynucleated cells in cerebrospinal fluid. Random forest regression model presented that the overall prediction power of severity reached 0.806, among which the number of polynucleated cells in cerebrospinal fluid contributed the most. Potential pathogenic causes exhibited that the proportion of mycoplasma was the highest, followed by Epstein-Barr virus. Conclusion: Our findings provided evidence for early identification of autoimmune encephalitis in children, especially in severe cases. [ABSTRACT FROM AUTHOR]

To evaluate the performance of GeneXpert MTB/RIF (Xpert) for tuberculous meningitis (TBM) and to identify additional indicators to improve diagnostic accuracy. An accuracy study was conducted. During 2011-2019, 243 TBM with 140 non-TBM in three TB-designated facilities in China were enrolled. Microbiological evidence of M tuberculosis (Mtb) in CSF was used as the reference. Additional indicators were identified by Boosted-Classification and Regression Tree (CART), the improvement of diagnostic performance was evaluated by ROC. The diagnostic sensitivity of Xpert was 71.1 % for definite TBM, and 5.5 % for probable/possible TBM. The positive rate of Xpert was improved with cerebrospinal fluid (CSF) increasing volume and was associated with CSF color (yellow). The additional indicators obtained by CART were CSF lactate and glucose and increased the sensitivity to 96.1 % (definite TBM) and 84.6 % (probable/possible TBM). The diagnostic performance of Xpert was satisfactory in definite TBM and would significantly be improved by the additional use of CSF lactate and glucose. [ABSTRACT FROM AUTHOR]

Background: Miliary tuberculosis (TB) is one of the severest manifestations of TB that can be lethal when concomitant with the central nervous system (CNS) involvement. Bacteriological, biochemical and radiological methods for find CNS comorbidity in miliary TB was evaluated in this study.Methods: Consecutive miliary TB adults were retrospectively enrolled from two designated TB hospitals in China. The capacities of examinations of cerebrospinal fluid (CSF), cerebral computed tomography (CT) and magnetic resonance imaging (MRI) for diagnosis of CNS involvement were assessed.Results: Assessment of CNS involvement with a lumbar puncture and/or neuroimaging was undertaken in 282 out of 392 of acute miliary TB. Of these 282 patients, 87.59% (247/282) had CNS involvement. Cerebral contrast-enhanced MRI (96.05%, 170/177) and MRI (93.15%, 204/219) yielded significantly higher sensitivities over CSF examination (71.92%, 146/203, P < 0.001) and CT (34.69%, 17/49, P < 0.001). The sensitivity of CSF examination was superior to CT scan (P < 0.001). Although 59.65% (134/225) miliary TB patients acquired bacteriological evidence with sputum examination, the positivity was only 8.82% (21/238) for CSF examination by conventional and molecular tests.Conclusion: Almost all miliary TB had CNS involvement and MRI demonstrated outstanding potential over other methods. Therefore, a routinely screening of CNS TB should be strongly suggested in miliary TB and MRI could be used as the initial approach in resources rich settings. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the activity, resistance, clonality of MIC distribution, and the correlation between virulence and resistance genes and biofilm formation of omadacycline (OMC) in clinics for Streptococcus agalactiae isolates from China. 162 isolates were collected retrospectively in China. The S. agalactiae were collected from the body's cervical secretions, wound secretions, ear swabs, secretions, semen, venous blood, cerebrospinal fluid, pee, etc. The MIC of OMC against S. agalactiae was determined by broth microdilution. The inhibition zone diameters of OMC and other common antibiotics were measured using filter paper. D-test was performed to determine the phenotype of cross resistance between erythromycin and clindamycin. In Multilocus sequence typing (MLST), some commonly-detected resistance genes and virulence gene of these S. agalactiae isolates were investigated using polymerase chain reaction (PCR). Biofilms were detected by crystal violet staining. Our data demonstrated the correalation of the biofilm formation and OMA antimicrobial susceptibility of S.agalactiae clinical isolates with the carrier of virulence gene scpB. Conclusively, OMC exhibits the robust antimcirobial activity against clinical S. agalactiae isolates from China compared with DOX or MIN, and the carrier of the virulence gene scpB might correlate with the biofilm formation in OMC-resistant S. agalactiae. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is one of the primary sequelae affecting the quality of life of patients with Japanese encephalitis (JE). The clinical treatment is mainly focused on life support, lacking of targeted treatment strategy.Methods: A cerebrospinal fluid (CSF) proteomic profiling study was performed including 26 patients with JE in Gansu province of China from June 2017 to October 2018 and 33 other concurrent hospitalized patients who were excluded central nervous system (CNS) organic or CNS infection diseases. The clinical and proteomics data of patients with JE were undergoing combined analysis for the first time.Results: Two subtypes of JE associated with significantly different prognoses were identified. Compared to JE1, the JE2 subtype is associated with lower overall survival rate and a higher risk of cognitive impairment. The percentages of neutrophils (N%), lymphocyte (L%), and monocytes (M%) decreased in JE2 significantly.Conclusions: The differences in proteomic landscape between JE subgroups have specificity for the prognosis of cognitive impairment. The data also provided some potential target proteins for treatment of cognitive impairments caused by JE. Trial registration ChiCTR, ChiCTR2000030499. Registered 1st June 2017, http://www.medresman.org.cn/pub/cn/proj/projectshow.aspx?proj=6333. [ABSTRACT FROM AUTHOR]

Background. Parkinson's disease (PD) is a neurodegenerative disease, a hallmark by the formation of misfolded and aggregated α-synuclein proteins. The expression of potential microRNA (miRNA) candidates isolated from serum and cerebrospinal fluid (CSF) exosomes of PD patients was assessed for their diagnostic value and their potential role as biomarkers for PD was explored. In this study, we characterize the expression level of miRNAs in the exosomes of blood sera and cerebrospinal fluid and explore their potential role as biomarkers for PD. Materials and Methods. A total of 209 patients having an onset of PD, along with 60 neurodegenerative (ND) disorders and 50 healthy controls were enrolled. Blood samples and CSF samples were collected and exosomes were isolated. The isolated exosomes were characterized using CD63 detection and exosomal RNA was extracted. Serum miRNA profiling was carried out by synthesizing cDNA from the purified RNA and miRNA transcripts were determined by qRT-PCR using SYBR Green PremixScript. microRNA profiling strategy was employed for extracting the exosomal miRNAs from the exosomes. Results. Five common miRNAs viz. miR-151a-5p, miR-24, mir-485-5p, mir-331-5p, and mir-214 were found to be upregulated with statistical significance in both the serum exosome and CSF exosomes. The investigation revealed that serum and CSF exosomal miRNA molecules are definitive biomarkers for PD with proper specificity and sensitivity. Conclusions. The significant level of miR-151a-5p, miR-24, mir-485-5p, mir-331-5p, and mir-214 was observed in the serum and CSF which may be established as a biomarker for the diagnosis of PD. [ABSTRACT FROM AUTHOR]

Background: Tuberculous meningitis (TBM) is the most serious form of extrapulmonary tuberculosis caused by Mycobacterium tuberculosis , and is characterized by high morbidity and mortality. Unfortunately, it is difficult to distinguish TBM from bacterial meningitis (BM) based on clinical features alone. The latest diagnostic tests and neuroimaging methods are still not available in many developing countries. This study aimed to develop a simple diagnostic algorithm based on clinical and laboratory test results as an early predictor of TBM in South China. Methods: A retrospective study was conducted to compare the clinical and laboratory characteristics of 114 patients with TBM and 47 with BM. Multivariate logistic regression analysis was performed on the characteristics of independently predicted TBM to develop a new diagnostic rule. Results: Five characteristics were predictive of a diagnosis of TBM: duration of symptoms before admission; tuberculous symptoms; white blood cell (WBC) count, total cerebrospinal fluid WBC count, and cerebrospinal fluid chloride concentration. The sensitivity and specificity of the new scoring system developed in this study were 81.6 and 93.6%, respectively. Conclusion: The new scoring system proposed in this study can help physicians empirically diagnose TBM and can be used in countries and regions with limited microbial and radiological resources. [ABSTRACT FROM AUTHOR]

Myodural bridges (MDB) are anatomical connections between the suboccipital muscles and the cervical dura mater which pass through both the atlantooccipital and the atlantoaxial interspaces in mammals. In our previous studies, we found that the MDB exists in seven terrestrial mammal species, two marine mammal species, two reptilian species, and one bird species. A recent study suggested that given the “ubiquity” of myodural bridges in terrestrial vertebrates, the MDB may also exist in snakes. Specifically, we focused on the Gloydius shedaoensis, a species of Agkistrodon (pit viper snake) that is only found on Shedao Island, which is in the southeastern sea of Dalian City in China. Six head and neck cadaveric specimens of Gloydius shedaoensis were examined. Three specimens were used for anatomical dissection and the remaining three cadaveric specimens were utilized for histological analysis. The present study confirmed the existence of the MDB in the Gloydius shedaoensis. The snake’s spinalis muscles originated from the posterior edge of the supraoccipital bones and the dorsal facet of the exocciput, and then extended on both sides of the spinous processes of the spine, merging with the semispinalis muscles. On the ventral aspect of this muscular complex, it gave off fibers of the MDB. These MDB fibers twisted around the posterior margin of the exocciput and then passed through the atlantooccipital interspace, finally terminating on the dura mater. We observed that the MDB also existed in all of the snakes’ intervertebral joints. These same histological findings were also observed in the Gloydius brevicaudus, which was used as a control specimen for the Gloydius shedaoensis. In snakes the spinal canal is longer than that observed in most other animals. Considering the unique locomotive style of snakes, our findings contribute to support the hypothesis that the MDB could modulate cerebrospinal fluid (CSF) pulsations. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae is a common human pathogen that can cause severe invasive pneumococcal diseases (IPDs). Penicillin-binding proteins (PBPs) are the targets for β-lactam antibiotics (BLAs), which are the common empirical drugs for treatment of pneumococcal infection. This study investigated the serotype distribution and antibiotic resistance patterns of S. pneumoniae strains causing IPD in China, including exploring the association between penicillin (PEN) susceptibility and PBPs variations. A total of 300 invasive S. pneumoniae isolates were collected from 27 teaching hospitals in China (2010-2015). Serotypes were determined by Quellung reaction. Serotypes 23F and 19F were the commonest serotypes in isolates from cerebrospinal fluid (CSF), whilst serotypes 19A and 23F were most commonly seen in non-CSF specimens. Among the 300 invasive S. pneumoniae strains, only one strain (serotype 6A, MIC = 0.25 μg/ml) with PEN MIC value ≤ 0.25 μg/ml did not have any substitutions in the PBPs active sites. All the strains with PEN MIC value ≥ 0.5 μg/ml had different substitutions within PBPs active sites. Substitutions in PBP2b and PBP2x active sites were common in low-level penicillin-resistant S. pneumoniae (PRSP) strains (MIC = 0.5 μg/ml), with or without PBP1a substitution, while all strains with PEN MIC ≥ 1 μg/ml had substitutions in PBP1a active sites, accompanied by PBP2b and PBP2x active site substitutions. Based on the three PBPs substitution combinations, a high degree of diversity was observed amongst the isolates. This study provides some new insights for understanding the serology and antibiotic resistance dynamics of S. pneumoniae causing IPD in China. However, further genomic studies are needed to facilitate a comprehensive understanding of antibiotic resistance mechanisms of S. pneumoniae. [ABSTRACT FROM AUTHOR]

This study aimed to explore the correlation of elevated glucose levels in the blood and cerebrospinal fluid with the progression and short-term prognosis of Guillain-Barré syndrome (GBS). The medical records of 982 patients who were diagnosed with GBS in 31 representative tertiary hospitals, located in 14 provinces in southern China, were collected and retrospectively reviewed. Patients were grouped according to the levels of fasting plasma glucose (FPG) and cerebrospinal fluid (CSF) glucose, as well as the concentration of blood hemoglobinAlc (HbA1c). The Hughes grade scale was used to quantify functional outcomes. Compared to patients with normal FPG and CSF glucose levels, those in the high FPG and high CSF glucose groups were characterized by a higher proportion of severe patients (HFGS ≥ 3) at admission (58.8 vs. 73.1, P = 0.000; 57.6 vs. 71.2, P = 0.000), at nadir (67.4 vs. 83.0, P = 0.000; 66.2 vs. 80.4, P = 0.000), and at discharge (29.8 vs. 46.3, P = 0.000; 26.4 vs. 45.0, P = 0.000). Patients in the high HbA1c group also had more severe disability at admission (74.6 vs. 56.1, P = 0.005) and at nadir (80.3 vs. 64.3, P = 0.012) compared to the normal HbA1c group. Moreover, elevated levels of FPG and CSF glucose were significantly correlated with more severe disability at admission, at nadir, and at discharge. The present study showed that elevated glucose levels in the blood and cerebrospinal fluid were associated with the severity and short-term prognosis of GBS. chicTR-RRc-17,014,152. GBS, Guillain-Barré syndrome; FPG, fasting plasma glucose; CSF, cerebrospinal fluid; HFGS, Hughes Functional Grading Scale; HbA1c, hemoglobin A1c. DM, diabetes mellitus; NCS, nerve conduction study; AIDP, acute inflammatory demyelinating polyneuropathy; AMAN, acute motor axonal neuropathy; AMSAN, acute motor sensory axonal neuropathy; MV, mechanical ventilation. [ABSTRACT FROM AUTHOR]

Objectives: Anti-dipeptidyl–peptidase–like protein 6 (anti-DPPX) encephalitis an extremely rare type of immune-mediated encephalitis. This study aimed to analyze the electroclinical characteristics and prognosis of anti-DPPX encephalitis. Methods: Five patients (all male) with anti-DPPX encephalitis in East China from January 2016 to October 2021 was retrospective analyzed. Electroclinical features and outcomes were reviewed. Results: All five patients were male. The media age at disease onset was 32 years old with a range of 14–56 years. The main symptoms included psychiatric disturbances (2/5), amnesia (4/5), confusion (3/5), and seizures (3/5). Migrating myoclonus were identified in patient 4 with positive DPPX and contactin-associated protein-like 2 antibodies in blood. All of the patients had positive DPPX antibodies in serum. Only one of them had positive antibody in the cerebrospinal fluid. EEG showed diffuse slowing in two patients, but no epileptiform discharges were observed. Eighty percent (4/5) of the patients showed normal brain magnetic resonance imaging. After immunotherapy, improvement of neuropsychiatric symptoms from all of the patients was observed. Over a mean follow-up of 30.8 weeks, all of the patients had marked improvement in the modified Rankin Scale. To date, no tumors were not observed in any patients. Conclusions: Anti-DPPX encephalitis mainly presents as neuropsychiatric symptoms. Cooperation of DPPX antibodies and CASPR2 antibodies might have contributed to the migration of myoclonus in the patient 4. Prompt immunotherapy often results in improvement. [ABSTRACT FROM AUTHOR]

Objective: To provide evidence for the diagnosis of listeriosis through a retrospective study of clinical features and results of pregnant women infected with listeriosis. Methods: Twenty‐nine pregnant women infected with listeriosis visiting West China Second University Hospital affiliated to Sichuan University from July 2010 to February 2019 were included in the retrospective analysis. Data like general information, clinical symptoms, laboratory results, and pathogen detection were analyzed to conclude clinical characteristics. Results: The median age of 29 patients was 28 (18.0–42.0). Nine individuals visited in the second trimester, while 20 in the last trimester. The median course before visiting was 3.4 (0.1–19) days. The main symptoms of the first attendance were fever (21/29), increased white blood cells (26/29), abdominal pain (16/29), and decreased or vanished fetal movements (7/29). Samples where listeria were identified were maternal blood (14 cases), excreta from birth canal (24 cases), placenta (one case), newborn blood (seven cases), newborn sputum (eight cases), newborn excreta from auditory meatus (three cases), cerebrospinal fluid (two cases) and ocular discharge (one case). Inflammation was detected in pathological examination of placenta in all subjects. Among them, three were diagnosed with mild chorioamnionitis; five with moderate chorioamnionitis; nine with moderate‐to‐severe chorioamnionitis and 12 with severe chorioamnionitis. Among 33 fetuses carried by 29 subjects, fetal outcomes include six miscarriages, nine stillbirths, four newborn deaths immediately after birth and four after treatment discontinuation, nine discharges after successful treatment in hospital, and one death after treatment. As for maternal outcomes, 29 pregnant women all recovered after delivery. Conclusion: With the acute onset, high incidence of adverse pregnancy outcomes and low coverage of initial treatment, clinical physicians need to raise the awareness of listeriosis during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Primary amoebic meningoencephalitis (PAM) is a rare, acute and fatal disease of the central nervous system caused by infection with Naegleria fowleri (Heggie, in Travel Med Infect Dis 8:201-6, 2010). Presently, the majority of reported cases in the literature have been diagnosed through pathogen detection pathogens in the cerebrospinal fluid (CSF). This report highlights the first case of pediatric PAM diagnosed with amoeba infiltration within CSF and bloodstream of an 8-year-old male child, validated through meta-genomic next-generation sequencing (mNGS).Case Presentation: An 8-year-old male child was admitted to hospital following 24 h of fever, headache and vomiting and rapidly entered into a coma. CSF examination was consistent with typical bacterial meningitis. However, since targeted treatment for this condition proved to be futile, the patient rapidly progressed to brain death. Finally, the patient was referred to our hospital where he was confirmed with brain death. CSF and blood samples were consequently analyzed through mNGS. N. fowleri was detected in both samples, although the sequence copy number in the blood was lower than for CSF. The pathogen diagnosis was further verified by PCR and Sanger sequencing.Conclusions: This is the first reported case of pediatric PAM found in mainland China. The results indicate that N. fowleri may spread outside the central nervous system through a damaged blood-brain barrier. [ABSTRACT FROM AUTHOR]

In this study, we intended to describe a human case of lumbosacral canal sparganosis in People's Republic of China (China). A 56-year-old man was admitted to Xiangya Hospital Central South University in Changsha, Hunan province, China after having an experience of perianal pain for a week. An enhancing mass, a tumor clinically suggested, was showed at the S1-S2 level of the lumbosacral spine by the examination of magnetic resonance imaging (MRI) with gadolinium contrast. The patient was received the laminectomy from S1 to S2, and an ivory-white living worm was detected in inferior margin of L5. In ELISA-test with cerebrospinal fluid (CSF) and serum samples, anti-sparganum antibodies were detected. He had a ingesting history of undercooked frog meat in his youth. By the present study, a human case of spinal sparganosis invaded in lumbosacral canal at the S1-S2 level was diagnosed in China. Although the surgical removal of larvae is known to be the best way of treatment for sparganosis, we administered the high-dosage of praziquantel, albendazole and dexamethasone to prevent the occurrence of another remain worms in this study. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to investigate the changing epidemiology and antimicrobial susceptibility of bacteria isolated from cerebrospinal fluid (CSF) in the Shandong region., Methodology: We conducted a retrospective analysis of bacterial distribution and resistance patterns in CSF samples, utilizing data from the SPARSS network and analyzed with WHONET 5.6 software., Results: A total of 3968 pathogenic bacterial strains were isolated, consisting of 70.6% Gram-positive bacteria, 27.2% Gram-negative bacteria, and 0.2% fungi. The six most commonly detected bacteria were coagulase-negative staphylococcus, Acinetobacter baumannii, Klebsiella pneumoniae, Streptococcus pneumoniae, Escherichia coli, and staphylococcus aureus. Analysis revealed gender and seasonal variations in the distribution of CSF pathogens, with a higher incidence observed in males and during autumn compared to other seasons. The susceptibility profiles of these bacterial species varied significantly, with many exhibiting multidrug resistances. A. baumannii showed a high resistance rate to cephalosporins and carbapenems but was sensitive to tigecycline and polymyxins. For treating multidrug-resistant A. baumannii infections, polymyxin-based combinations with tigecycline or sulbactam are recommended for adults, while tigecycline combined with meropenem is suggested for children. Enterobacteriaceae species were generally sensitive to carbapenems, such as meropenem and other carbapenems that can penetrate the blood-brain barrier can be recommended. Linezolid and vancomycin are the first choice for treating common gram-positive bacterial infections., Conclusions: The high resistance rates observed among common CSF isolates and their varied distributions across different demographics highlight the necessity for customized treatment strategies., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Chunyan Zhang, Zheng Li, Mengyuan Wang, Shifu Wang.)

Objectives: Impulsive behavior is the precursor of many psychiatric and neurological conditions. High levels of impulsive behavior will increase health risk behavior and related injuries. Impulsive behavior is produced and regulated by central and peripheral biological factors, and oxidative stress (OS) can aggravate it. However, previous studies only showed that impulsive behavior was related to the level of the peripheral OS. Therefore, this study aims to clarify the relationship between OS and impulsive behavior in the brain and peripheral blood., Methods: We recruited 64 Chinese men. We measured superoxide dismutase (SOD) (including copper, zinc and manganese) and nitric oxide synthase (NOS) (including total, inducible and constitutive) in cerebrospinal fluid (CSF) and plasma. The Barratt Impulsiveness Scale version 11 (BIS-11) was used to evaluate impulsive behavior. The relationship between OS and impulsive behavior was evaluated by partial correlation analysis and stepwise multiple regression analysis., Results: Partial correlation analysis showed that the ratio of total NOS-to-MnSOD and iNOS-to-MnSOD in CSF were negatively correlated with the BIS-11 motor scores (r = -0.431, p = -0.001; r = -0.434, p = -0.001). Stepwise multiple regression analysis showed that the ratio of CSF iNOS-to-MnSOD was the most influential variable on the BIS-11 motor scores(β = -0.434, t = -3.433, 95 %CI(-0.374, -0.098), p = 0.001)., Conclusions and Relevance: The imbalance of central oxidation and antioxidation is related to impulsive behavior, which broadens our understanding of the correlation between impulsive behavior and OS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective To explore the diagnostic value of the coagulation marker D-dimer and its combination with the traditional marker C-reactive protein (CRP) in distinguishing bacterial meningitis (BM) from tuberculous meningitis (TM). Methods We performed a retrospective study on specimens from 173 patients with meningitis who were hospitalized at the First Affiliated Hospital of Guangxi Medical University, Guangxi, China, from 2012 through 2020. The patient records were divided into the BM group and the TM group, and hematological parameters D-dimer and CRP were evaluated for the 2 groups. Results The levels of D-dimer and CRP in the BM group were significantly higher than those levels in the TM group (P ˂.001 for each), and the sensitivity and specificity of the combined detection of the 2 markers was 86.3% to 100%; the area under the receiver operating characteristic (ROC) curve reached 0.983 (95% confidence interval [CI], 0.966–0.999). Conclusion D-dimer testing has high specificity in distinguishing between BM and TM; CRP testing also has high sensitivity. The combined diagnosis of the 2 biomarkers helps to distinguish TM from BM. [ABSTRACT FROM AUTHOR]

Background/objective: Severe fever with thrombocytopenia syndrome (SFTS) cause encephalitis/encephalopathy, but few reports were available. We aimed to investigate the incidence of encephalitis/encephalopathy in SFTS patients and to summarize clinical characteristics, laboratory findings and imaging features.Methods: We conducted a retrospective review of all patients with confirmed SFTS admitted to Nanjing Drum Tower Hospital, a tertiary hospital in Nanjing City, China, between January 2016 and July 2020. The patients were divided into two groups according to whether they had encephalitis/encephalopathy: encephalitis/encephalopathy group and non- encephalitis/encephalopathy group. Clinical data, laboratory findings, imaging characteristics, treatments and outcomes of these patients were collected and analyzed.Results: A total of 109 SFTS patients with were included, of whom 30 (27.5 %) developed encephalitis/encephalopathy. In-hospital mortality (43.3 %) was higher in encephalitis/encephalopathy group than non-encephalitis/encephalopathy group (12.7 %). Univariate logistic regression showed that cough, wheezing, dyspnoea, respiratory failure, vasopressors use, bacteremia, invasive pulmonary aspergillosis (IPA) diagnoses, PCT > 0.5 ug/L, CRP > 8 mg/L, AST > 200 U/L and serum amylase level > 80 U/L were the risk factors for the development of encephalitis/encephalopathy for SFTS patients. Multivariate logistic regression analysis identified bacteremia, PCT > 0.5 mg/L and serum amylase level > 80 U/L as independent predictors of encephalitis/ encephalopathy development for SFTS patients.Conclusions: SFTS-associated encephalitis/encephalopathy has high morbidity and mortality. it was necessary to strengthen the screening of CSF testing and brain imaging after admission for SFTS patients who had symptoms of encephalitis/encephalopathy. SFTS patients with bacteremia, PCT > 0.5 ug/L or serum amylase level > 80 U/L should be warned to progress to encephalopathy. [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic normal pressure hydrocephalus (iNPH) is one of the potentially reversible dementias. Early and accurate diagnosis is important for patients' prognosis. Emerging evidence shows fluid biomarkers are useful in diagnosis and pathophysiological research of iNPH. Methods: Probable iNPH and Alzheimer's disease (AD) patients were recruited. Clinical diagnosis was performed according to international guidelines. CSF collection complied with a standard protocol. Commercial accessible ELISA kits were introduced for measurement of CSF t-tau, p-tau181, Aβ42, and NfL. Results: Twenty-seven iNPH, 27 AD, and 18 controls were included. The profiles of CSF t-tau, p-tau181, and t-tau/Aβ42 in the iNPH and AD were significantly different (p < 0.0001). The profiles of CSF t-tau, p-tau181, and t-tau/Aβ42 in the iNPH and control were not different (p > 0.05). Level of CSF Aβ42 in iNPH was significantly lower than control (p < 0.0001) and also significantly higher than AD (p < 0.05). NfL level in iNPH and AD was increased, but its level in iNPH was significantly lower than that in AD (p = 0.005). NfL and t-tau level in the iNPH group was significantly correlated (coefficient = 0.649, p = 0.005), but not in AD (coefficient = 0.298, p = 0.157). Conclusion: Alzheimer's CSF biomarker profile of iNPH subjects showed moderately decreased Aβ42 and normal t-tau, p-tau181, and t-tau/Aβ42, which was distinguishable from AD. The different profiles and correlation of t-tau and NfL suggested different pathophysiology of AD and iNPH. t-tau was relatively an AD-specific neurodegenerative biomarker compared to NfL. [ABSTRACT FROM AUTHOR]

Background: The relationship between alcohol consumption and Alzheimer's disease (AD) pathology is unclear. Amyloid-β (Aβ) and tau biomarkers in cerebrospinal fluid (CSF) have been proven valuable in establishing prognosis in pre-clinical AD.Objective: We sought to examine the associations between alcohol consumption and CSF AD biomarkers in cognitive intact subjects.Methods: A total of 806 cognitively intact participants who had measurements of CSF Aβ, pTau, and total Tau proteins and drinking characteristics were included from the Chinese Alzheimer's Biomarker and Lifestyle (CABLE) study. Linear and logistic regression analyses were utilized to explore the associations of alcohol consumption with CSF AD biomarkers. We examined the interaction effects of age, gender, and apolipoprotein epsilon (APOE) ɛ4 status on the relationships between the frequency of drinking and CSF biomarkers.Results: The multiple linear regression analyses revealed significant differences in CSF AD biomarkers between infrequent drinking (< 1 times/week) and frequent drinking groups (≥1 times/week). Participants in frequent drinking group had higher CSF p-tau/Aβ42 and tTau/Aβ42. Frequent drinking was significantly associated with greater pTau and tTau abnormalities compared to the infrequent drinking group in older (> 65 years) participants.Conclusion: The present study showed significant associations between drinking frequency and CSF AD biomarkers in cognitively intact older adults. Alcohol consumption may have an influence on AD by modulating amyloid deposition and tau phosphorylation in the preclinical stage. [ABSTRACT FROM AUTHOR]

Background and objective Tumor markers (TM) in cerebrospinal fluid (CSF) are useful for diagnosing leptomeningeal metastasis (LM). It has not been fully exploited the diagnostic possibilities of the CSF levels since the basic fact that the TM concentration of CSF depends strongly upon the serum levels as well as upon the condition of the blood brain barrier (BBB). To analyze the intrathecal TM synthesis and evaluate the integrity of BBB can be helpful for the definitive diagnosis of LM. Therefore, the aim of this study was to further explore the clinical value of intrathecal TM synthesis and BBB in the diagnosis for the lung cancer patients with LM. Methods Twenty-five lung cancer patients with LM and 57 patients with nonmalignant neurological diseases (NMNDs) admitted to Nanjing Drum Tower Hospital from December 2016 to March 2020 were included. We compared the integrity of BBB and intrathecal TM synthesis between two groups, analyzed the correlation of CSF TM between the detection and intrathecal synthesis, and evaluated serial CSF cytology, the integrity of BBB and intrathecal TM synthesis when intrathecal chemotherapy for one patient. Results Ninety-four percent LM patients showed the dysfunction of BBB, and all LM patients showed at least one intrathecal synthesized TM in CSF. In one patient, the CSF cytology was negative for the first time, but LM was eventually diagnosed based on the the intrathecal TM synthesis and positive CSF cytology of repeated lumbar puncture. In LM group, no correlation was observed between the detection and intrathecal synthesized TM in CSF. In the control group, only 3.5% (2/57) NMNDs patients had the dysfunction of BBB and no patients had intrathecal TM synthesis, both the differences of which were statistically significant (P<0.05). Finally, evaluating the CSF cytology, integrity of BBB and intrathecal TM synthesis can be used to assess the intracranial treatment effect. Moreover, intrathecal TM synthesis changes earlier than cytology. Conclusion The evaluation of intrathecal TM synthesis and integrity of BBB are novel clinical diagnostic tools. In addition, serial measurement of intrathecal synthesized TM may play an important role in monitoring efficacy of lung cancer patients with LM, which is worthy of further promotion and clinical application. [ABSTRACT FROM AUTHOR]

Background: Cerebrospinal fluid (CSF) biomarkers are widely accepted as manifestations of Alzheimer's disease (AD) pathogenesis and incorporated into biological definition of AD. However, the correlations between CSF and other biomarkers such as neuroimaging and neuropsychiatric evaluation are complicated and inconsistent.Objective: We aimed to better interpreting CSF biomarkers results accompanying with other indexes in improving accurate diagnosis of AD.Methods: 112 AD patients and 30 cognitive normal controls were selected. Commercial accessible ELISA kits were introduced for measurement of CSF t-tau, p-tau181, Aβ1-42, and NfL based on standard protocol. MRI examinations were performed using a 3-T MRI scanner and visual rating scales including medial temporal atrophy score and Koedam's scale were used to evaluate medial temporal atrophy and posterior region atrophy.Results: CSF biomarkers' profile including decreased concentration of Aβ1-42, increased concentration of t-tau, p-tau181, t-tau/Aβ 1-42, and NfL were diagnostic between AD and control. CSF biomarkers profile was not influenced by the APOE genotype. Increased concentration of t-tau and NfL, as well as ratio of t-tau/Aβ 1-42 were related to decrease of Mini-Mental State Examination (MMSE) score while concentration of Aβ1-42 not. Visual assessed cortical atrophy was related to MMSE score, but most of the CSF biomarkers were not related to atrophy, except that increased concentration of p-tau181 was significantly associated with atrophy of posterior cortical region.Conclusion: Our results supported CSF biomarkers were helpful in diagnosis of AD. However, CSF biomarkers were cross-sectional reflection of pathogenesis, which did not correlate well with clinical progression. CSF biomarkers should be interpreted in combination with MRI and cognitive evaluation in clinical use. [ABSTRACT FROM AUTHOR]