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Introduction: Toward further cerebro-spinal flow quantification in clinical practice, this study aims at assessing the variations in the cerebro spinal fluid flow pattern associated with change in the morphology of the subarachnoid space of the cervical canal of healthy humans by developing a computational fluid dynamics model. Methods: 3D T2-space MRI sequence images of the cervical spine were used to segment 11 cervical subarachnoid space. Model validation (time-step, mesh size, size and number of boundary layers, influences of parted inflow and inflow continuous velocity) was performed a 40-year-old patient-specific model. Simulations were performed using computational fluid dynamics approach simulating transient flow (Sparlart-Almaras turbulence model) with a mesh size of 0.6, 6 boundary layers of 0.05 mm, a time step of 20 ms simulated on 15 cycles. Distributions of components velocity and WSS were respectively analyzed within the subarachnoid space (intervertebral et intravertebral levels) and on dura and pia maters. Results: Mean values cerebro spinal fluid velocity in specific local slices of the canal range between 0.07 and 0.17 m.s-1 and 0.1 and 0.3 m.s-1 for maximum values. Maximum wall shear stress values vary between 0.1 and 0.5 Pa with higher value at the middle of the cervical spine on pia mater and at the lower part of the cervical spine on dura mater. Intra and inter-individual variations of the wall shear stress were highlighted significant correlation gwith compression ratio (r = 0.76), occupation ratio and cross section area of the spinal cord. Conclusion: The inter-individual variability in term of subarachnoid canal morphology and spinal cord position influence the cerebro-spinal flow pattern, highlighting the significance of canal morphology investigation before surgery. [ABSTRACT FROM AUTHOR]

Background: Meningitis poses a significant challenge to public health in low-income nations, such as Ethiopia, with a particular impact on newborns. The magnitude and etiologies of meningitis vary based on geographic location and age of patients. There is limited data regarding the magnitude and etiology of meningitis from Sidama Regional State, Ethiopia. This study aimed to determine the magnitude and bacterial profile of meningitis among newborns aged less than 90 days at Hawassa University Comprehensive Specialized Hospital (HUCSH). Methods: A retrospective cross-sectional study was conducted among newborns under 90 days who were suspected of meningitis at HUCSH from January 2019 to July 2023, and for whom Cerebrospinal fluid (CSF) culture was performed. At HUCSH, bacteria are isolated and identified using standard microbiological techniques. Socio-demographic characteristics and culture results were extracted from the laboratory register. Data were entered into Excel and exported it to SPSS version 20 for analysis. Results: Overall 1061 newborns suspected of meningitis were included in the study. Among the participants, 767 individuals (72.3%) fell within the age range of 8 to 90 days. Of the total participants, 437 (41.2%) were females. The magnitude of culture-confirmed meningitis was 90(8.5%) 95% CI: 6.8%−10.1%. The magnitude of culture-confirmed meningitis among newborns aged 0−7 days and 8−90 days were 1.6% and 6.9% respectively. The proportion of bacteria among newborns aged 0−7 days and 8−90 days were 18.9% and 81.1% respectively. Coagulase-negative Staphylococci (CONS) were the most common bacteria (n = 26; 28.9%) recovered followed by Acinetobacter species (n = 12, 13.3%), Escherichia coli (n = 9; 10%), and Klebsiella pneumoniae (n = 7; 7.8%). K. pneumoniae was the predominant bacteria among newborns within the age group of 0 to 7 days while Acinetobacter species was the most common among newborns within the 8 to 90 days age group. The prevalence of culture-confirmed neonatal meningitis was found to be greater in male newborns (x2 = 1.74, p = 0.18), newborns aged between 8 to 90 days (x2 = 0.07, p = 3.4), and newborns admitted in 2022 (x2 = 2.4, p = 0.66), Conclusions: In this study, the overall magnitude of culture-confirmed meningitis was relatively high. Culture-confirmed meningitis was high in newborns within the age range of 8 to 90 days. The most common bacteria were CONS in both age groups followed by Acinetobacter species, E. coli, and K. pneumoniae. [ABSTRACT FROM AUTHOR]

Background and objective: Multiple sclerosis (MS) is a chronic progressive autoimmune disorder of the central nervous system (CNS) that can cause inflammation, demyelination, and axon degeneration. Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide mainly synthesized in the liver and brain. IGF-1 causes neuronal and non-neuronal cell proliferation, survival, and differentiation. Therefore, it can be used in treating neuro-demyelinating diseases such as MS. The current systematic review and meta-analysis aims to compare the levels of IGF-1 in MS patients and healthy controls and also investigates IGF binding proteins (IGF-BP) and growth hormone (GH) levels between MS patients and healthy controls. Methods: In this study, we systematically searched electronic databases of PubMed, Scopus, Web of Science (WOS), and Google Scholar, up to December 2022. Studies that measured IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and healthy controls in either blood or cerebral spinal fluid (CSF) were identified. We calculated Standardized mean differences (SMD) to compare levels of IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and controls. Results: Finally, we included 11 eligible studies from 1998 to 2018. The sample size of included studies varied from 20 to 200 resulting in a total sample size of 1067 individuals, 531 MS patients, and 536 healthy controls. The mean age of the patient and control groups were 38.96 and 39.38, respectively. The average EDSS among patients was 4.56. We found that blood levels of IGF-1 (SMD = 0.20, 95% CI = -0.20 to 0.59, I2 = 82.4%, K = 8, n = 692), CSF level of IGF-1 (SMD = 0.25, 95% CI = -0.06 to 0.56, I2 = 0.0%, K = 3 n = 164) and blood levels of GH were not significantly higher in MS patients than controls (SMD = 0.08, 95% CI = -0.33 to 0.49, I2 = 77.0% K = 3, n = 421). Moreover, the blood levels of IGFBP-1 (SMD = 0.70, 95% CI = 0.01 to 1.40, I2 = 77%, K = 4, n = 255) were significantly higher in MS cases than in controls. However, the blood levels of IGFBP-2 (SMD = 0.43, 95% CI = -0.34 to 1.21, I2 = 64.2%, K = 3, n = 78) and blood levels of IGFBP-3 (SMD = 1.04, 95% CI = -0.09 to 2.17, I2 = 95.6%, K = 6, n = 443) were not significantly higher in patients than controls. Conclusion: Our meta-analysis revealed no significant difference in serum levels of IGF-1, GH, IGFBP-2, and IGFBP-3 between the MS group and healthy controls, except for IGFBP1. However, our systematic review showed that the studies were controversial for IGFBP-3 serum levels. Some studies found an increase in serum level of IGFBP-3 in MS patients compared to the healthy group, while others showed a decrease. [ABSTRACT FROM AUTHOR]

Objective: To determine trends in incidence, etiology and antimicrobial susceptibility of blood and cerebrospinal fluid (CSF) culture confirmed infections in hospitalized infants in a large tertiary neonatal unit in South Africa. Methods: Single-center, retrospective review of laboratory records of bacteria and fungi, and their susceptibility profiles, isolated from blood and CSF of infants hospitalized in the neonatal unit at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, from 1st January 2010 to 31st December 2019. Laboratory data on isolates and their antimicrobial susceptibilities were collected. Coagulase-negative Staphylococcus, Corynebacteria and Bacillus spp. were excluded. Patient-level clinical and laboratory data were not available. Results: There were 8,319 significant isolates, giving an infection rate of 14.3/1000 patient-days. Infection rates increased from 12.0 to 15.7/1000 patient-days (estimated average yearly change 0.6[95%CI, 0.5–0.7];p = <0.001). Gram-negative infection rates increased from 4.3 to 10.8/1000 patient-days (estimated average yearly change 0.7[95%CI,0.6–0.8];p = <0.001). The 2 most commonly isolated Gram-negative organisms were Acinetobacter baumannii (44%) and Klebsiella pneumoniae (39%). Carbapenem resistance was seen in 31% of all Gram-negatives and increased over time (estimated average yearly change 4.8%[95%CI,4.2%-5.3%];p<0.001). Gram-positive infection rates decreased (estimated average yearly change -0.1[95%CI,-0.2– -0.05];p = <0.001). Staphylococcus aureus was the most common Gram-positive isolated. Rates of methicillin-resistant Staphylococcus aureus decreased from 91% to 55%(estimated average yearly change -2.8%[95%CI,-3.5%–2%],p< 0.001). Rates of fungal isolates decreased (estimated average yearly change -0.06[95%CI,-0.1 –-0.02]);p = 0.007). Candida parapsilosis (52%) and Candida albicans (35%) were the most common fungi isolated. Conclusions: There has been a marked overall increase in rates of blood and/or CSF infections, with an absolute increase in Gram-negative infections observed, replacing Gram-positive and fungal pathogens. Extended spectrum beta-lactamase Gram-negative isolates are being replaced by carbapenem resistance, with around one third of all significant Gram-negative isolates now carbapenem resistant. Research into hospital based novel treatment and prevention interventions for neonatal sepsis should be urgently prioritized. [ABSTRACT FROM AUTHOR]

In steroid-responsive meningitis-arteritis (SRMA), inflammatory dysregulation is driven by neutrophilic granulocytes resulting in purulent leptomeningitis. Neutrophils can generate neutrophil extracellular traps (NET). Uncontrolled NET-formation or impaired NET-clearance evidently cause tissue and organ damage resulting in immune-mediated diseases. The aim of the study was to verify that NET-formation is detectable in ex vivo samples of acute diseased dogs with SRMA by visualizing and measuring NET-markers in serum and cerebrospinal fluid (CSF) samples. CSF-samples of dogs with acute SRMA (n = 5) and in remission (n = 4) were examined using immunofluorescence (IF)-staining of DNA-histone-1-complexes, myeloperoxidase and citrullinated Histone H3 (H3Cit). Immunogold-labeling of H3Cit and neutrophil elastase followed by transmission electron microscopy (TEM) were used to determine ultrastructural NET-formation in the CSF of one exemplary dog. H3Cit-levels and DNase-activity were measured in CSF and serum samples using an H3Cit-ELISA and a DNase-activity-assay, respectively in patients with the following diseases: acute SRMA (n = 34), SRMA in remission (n = 4), bacterial encephalitis (n = 3), meningioma with neutrophilic inflammation (n = 4), healthy dogs (n = 6). NET-formation was detectable with IF-staining in n = 3/5 CSF samples of dogs with acute SRMA but were not detectable during remission. Vesicular NET-formation was detectable in one exemplary dog using TEM. DNase-activity was significantly reduced in dogs suffering from acute SRMA compared to healthy control group (p < 0.0001). There were no statistical differences of H3Cit levels in CSF or serum samples of acute diseased dogs compared to dogs under treatment, dogs suffering from meningioma or bacterial encephalitis or the healthy control group. Our findings demonstrate that NET-formation and insufficient NET-clearance possibly drive the immunologic dysregulation and complement the pathogenesis of SRMA. The detection of NETs in SRMA offers many possibilities to explore the aetiopathogenetic influence of this defence mechanism of the innate immune system in infectious and non-infectious canine neuropathies. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel diseases (IBDs) with the subtypes ulcerative colitis (UC) and Crohn disease (CD), are chronic autoimmune inflammatory disorders of the gastrointestinal tract. Cytokines are associated with the development and progression in pediatric IBD. We measured cytokine levels in pediatric IBD patients to assess their potential function as biomarkers in disease assessment. Method: In this prospective cohort study, we enrolled 33 children with IBD. All patients were in stable remission for 3 months on enrollment. Patients who developed a relapse within six months after enrollment were classified as relapsers. Blood sampling was performed at enrolment and for relapsers in relapse and post-relapse. Serum concentrations of 14 cytokines, chemokines and growth factors (IL-1α, IL-1β, IL-6, IL-12p40, IP-10, TNF-α, IFN-γ, IL-10, IL-8, MIP-1α, MCP-1, MCP-3, G-CSF, GM-CSF) were measured simultaneously using multiplex bead-based sandwich immunoassay on Luminex 100 system. Results: MCP-1 was significantly higher in CD patients compared to UC patients at each disease stage: stable remission (P<0.048), unstable remission (P<0.013), relapse (P<0.026) and post-relapse (P<0.024). G-CSF was significantly increased in UC patients developing a relapse and in post-relapse stage compared to UC patients in remission (P<0.02 and p<0.03, respectively). Conclusion: MCP-1 showed potential as a diagnostic biomarker in CD patients independent of disease activity as it was able to discriminate between subtypes of pediatric IBD. In UC patients, G-CSF was significantly elevated in relapsers indicating its use and role as a potential prognostic biomarker. [ABSTRACT FROM AUTHOR]

Objectives: Encephalitis, brain inflammation and swelling, most often caused by an infection or the body's immune defences, can have devastating consequences, especially if diagnosed late. We looked for clinical predictors of different types of encephalitis to help clinicians consider earlier treatment. Methods: We conducted a multicentre prospective observational cohort study (ENCEPH-UK) of adults (> 16 years) with suspected encephalitis at 31 UK hospitals. We evaluated clinical features and investigated for infectious and autoimmune causes. Results: 341 patients were enrolled between December 2012 and December 2015 and followed up for 12 months. 233 had encephalitis, of whom 65 (28%) had HSV, 38 (16%) had confirmed or probable autoimmune encephalitis, and 87 (37%) had no cause found. The median time from admission to 1st dose of aciclovir for those with HSV was 14 hours (IQR 5–50); time to 1st dose of immunosuppressant for the autoimmune group was 125 hours (IQR 45–250). Compared to non-HSV encephalitis, patients with HSV more often had fever, lower serum sodium and lacked a rash. Those with probable or confirmed autoimmune encephalitis were more likely to be female, have abnormal movements, normal serum sodium levels and a cerebrospinal fluid white cell count < 20 cells x106/L, but they were less likely to have a febrile illness. Conclusions: Initiation of treatment for autoimmune encephalitis is delayed considerably compared with HSV encephalitis. Clinical features can help identify patients with autoimmune disease and could be used to initiate earlier presumptive therapy. [ABSTRACT FROM AUTHOR]

Background: Sysmex DI-60 (Sysmex, Kobe, Japan) is a digital morphology (DM) analyzer widely used in clinical laboratories and supports body fluid (BF) applications. We evaluated analytical performance of DI-60 compared with XN-350 (Sysmex) and manual counting for BF cell differential counts. Methods: A total of 213 BF samples were collected (47 cerebrospinal fluid [CSF], 80 pleural fluid, and 86 ascites samples). The analytical performance of DI-60 for BF cell differential counts was evaluated based on sensitivity, specificity, accuracy, and agreement. BF cell differential counts obtained by DI-60 were compared with those obtained by XN-350 and manual counting. Results: The overall sensitivity was high for neutrophils, lymphocytes, and macrophages (range, 83.1–99.4%). The overall specificity and overall accuracy were high for all cell types (range, 95.3–99.7% and 94.3–99.3%, respectively). The agreement between DI-60 pre-classification and verification was strong (κ = 0.89). The absolute mean differences between DI-60 verification and XN-350 ranged from 0.26 to 11.05, and differences between DI-60 verification and manual counting ranged from 0.01 to 4.76. Conclusions: This is the first study to evaluate the performance of DI-60 compared with XN-350 and manual counting for BF cell differential counts. DI-60 showed reliable performance with CSF, pleural fluid, and ascites samples. For BF cell differential counts, DI-60 may be a better option than XN-350 and could be used for screening purposes in understaffed laboratories. To improve the hematology workflow for BF cell differential counting, the DM analyzer needs to be optimized by taking into account the laboratory situation and unmet needs, and the clinical laboratory needs to establish criteria for verification and manual slide review. [ABSTRACT FROM AUTHOR]

Objective: To characterize the microbiota of the cerebrospinal fluid (CSF) from children with hydrocephalus at the time of initial surgical intervention. Study design: CSF was obtained at initial surgical intervention. One aliquot was stored in skim milk-tryptone-glucose-glycerol (STGG) medium and the second was unprocessed; both were then stored at –70°C. Bacterial growth for CSF samples stored in STGG were subsequently characterized using aerobic and anaerobic culture on blood agar and MALDI-TOF sequencing. All unprocessed CSF samples underwent 16S quantitative polymerase chain reaction (qPCR) sequencing, and a subset underwent standard clinical microbiological culture. CSF with culture growth (either after storage in STGG or standard clinical) were further analyzed using whole-genome amplification sequencing (WGAS). Results: 11/66 (17%) samples stored in STGG and 1/36 (3%) that underwent standard clinical microbiological culture demonstrated bacterial growth. Of the organisms present, 8 were common skin flora and 4 were potential pathogens; only 1 was also qPCR positive. WGAS findings and STGG culture findings were concordant for only 1 sample, identifying Staphylococcus epidermidis. No significant difference in time to second surgical intervention was observed between the STGG culture-positive and negative groups. Conclusion(s): Using high sensitivity methods, we detected the presence of bacteria in a subset of CSF samples at the time of first surgery. Therefore, the true presence of bacteria in CSF of children with hydrocephalus cannot be ruled out, though our findings may suggest these bacteria are contaminants or false positives of the detection methods. Regardless of origin, the detection of microbiota in the CSF of these children may not have any clinical significance. [ABSTRACT FROM AUTHOR]

Background: Predicting the long-term disability outcomes of multiple sclerosis (MS) cases is challenging. Objective: We prospectively analysed our previous MS cohort with initial cerebrospinal fluid (CSF) proteomics data to reveal disability markers after 8.2±2.2 years of follow-up. Methods: Patients with regular follow-up visits were assigned into two groups: those with an age-related MS severity (ARMSS) score ≥5 (unfavourable course group, N = 27) and ARMSS score <5 (favourable course group, N = 67). A machine learning-based algorithm was applied to reveal candidate poor prognosis-associated initial CSF proteins, which were measured in an independent MS cohort (verification group, N = 40) by ELISA. Additionally, the correlation of initial clinical and radiological parameters with long-term disability was analysed. Results: CSF alpha-2-macroglobulin (P = 0.0015), apo-A1 (P = 0.0016), and haptoglobin (P = 0.0003) protein levels, as well as cerebral lesion load (>9 lesions) on magnetic resonance imaging, gait disturbance (P = 0.04), and bladder/bowel symptoms (P = 0.01) were significantly higher in the unfavourable course group than in the favourable course group. Optic nerve involvement evident on initial magnetic resonance imaging (P = 0.002) and optic neuritis (P = 0.01) were more frequent in the favourable course group. Conclusion: The herein identified initial CSF protein levels, in addition to the clinical and radiological parameters at disease onset, have predictive value for long-term disability in MS cases. [ABSTRACT FROM AUTHOR]

In humans, the pituitary gland is covered by a fibrous capsule and is considered a continuation of the meningeal sheath. However, in rodents some studies concluded that only the pars tuberalis (PT) and pars nervosa (PN) are enwrapped by the pia mater, while others showed that the whole gland is covered by this sheath. At PT the median eminence subarachnoid drains cerebrospinal fluid (CSF) to its cisternal system representing a pathway to the hypothalamus. In the present study we examined the rat pituitary capsule to elucidate its configuration, its physical interaction with the pituitary border and its relationship with the CSF. Furthermore, we also revisited the histology of the pituitary cleft and looked whether CSF drained in it. To answer such questions, we used scanning and transmission electron microscopy, intracerebroventricular infusion of Evan´s blue, fluorescent beads, and sodium fluorescein. The latter was measured in the pars distalis (PD) and various intracranial tissues. We found a pituitary capsule resembling leptomeninges, thick at the dorsal side of the pars intermedia (PI) and PD, thicker at the level of PI in contiguity with the PN and thinner at the rostro-ventral side as a thin membrane of fibroblast-like cells embedded in a fibrous layer. The capsule has abundant capillaries on all sides. Our results showed that the CSFs bathe between the capsule and the surface of the whole gland, and ciliate cells are present in the pituitary border. Our data suggest that the pituitary gland intercommunicates with the central nervous system (CNS) through the CSF. [ABSTRACT FROM AUTHOR]

Background: Cognitive status classification (e.g. dementia, cognitive impairment without dementia, and normal) based on cognitive performance questionnaires has been widely used in population-based studies, providing insight into the population dynamics of dementia. However, researchers have raised concerns about the accuracy of cognitive assessments. MRI and CSF biomarkers may provide improved classification, but the potential improvement in classification in population-based studies is relatively unknown. Methods: Data come from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We examined whether the addition of MRI and CSF biomarkers improved cognitive status classification based on cognitive status questionnaires (MMSE). We estimated several multinomial logistic regression models with different combinations of MMSE and CSF/MRI biomarkers. Based on these models, we also predicted prevalence of each cognitive status category using a model with MMSE only and a model with MMSE + MRI + CSF measures and compared them to diagnosed prevalence. Results: Our analysis showed a slight improvement in variance explained (pseudo-R2) between the model with MMSE only and the model including MMSE and MRI/CSF biomarkers; the pseudo-R2 increased from.401 to.445. Additionally, in evaluating differences in predicted prevalence for each cognitive status, we found a small improvement in the predicted prevalence of cognitively normal individuals between the MMSE only model and the model with MMSE and CSF/MRI biomarkers (3.1% improvement). We found no improvement in the correct prediction of dementia prevalence. Conclusion: MRI and CSF biomarkers, while important for understanding dementia pathology in clinical research, were not found to substantially improve cognitive status classification based on cognitive status performance, which may limit adoption in population-based surveys due to costs, training, and invasiveness associated with their collection. [ABSTRACT FROM AUTHOR]

How cerebrospinal fluid (CSF) drains from the human brain is of paramount importance to cerebral health and physiology. Obstructed CSF drainage results in increased intra-cranial pressure and a predictable cascade of events including dilated cerebral ventricles and ultimately cell death. The current and accepted model of CSF drainage in humans suggests CSF drains from the subarachnoid space into the sagittal sinus vein. Here we identify a new structure in the sagittal sinus of the human brain by anatomic cadaver dissection. The CSF canalicular system is a series of channels on either side of the sagittal sinus vein that communicate with subarachnoid cerebrospinal fluid via Virchow-Robin spaces. Fluorescent injection confirms that these channels are patent and that flow occurs independent of the venous system. Fluoroscopy identified flow from the sagittal sinus to the cranial base. We verify our previous identification of CSF channels in the neck that travel from the cranial base to the subclavian vein. Together, this information suggests a novel path for CSF drainage of the human brain that may represent the primary route for CSF recirculation. These findings have implications for basic anatomy, surgery, and neuroscience, and highlight the continued importance of gross anatomy to medical research and discovery. [ABSTRACT FROM AUTHOR]

Background: Within the past 10 years, immune mechanisms associated with acute ischemic stroke (AIS) have been brought into focus, but data on B cell activation and intrathecal Ig production is still scarce. In this study, we determined the prevalence of an elevated IgG index, positive oligoclonal bands (OCBs) and chemokine C-X-C motif ligand 13 (CXCL13) levels in the cerebrospinal fluid (CSF) as markers of intrathecal IgG synthesis and B cell activation in patients with AIS. Methods: In a retrospective study we analyzed the cerebrospinal fluid (CSF) from 212 patients with AIS from December 2013 to May 2018 assessing intrathecal Ig synthesis, OCBs and CXCL13 concentrations. Results: Overall, 5.7% (12/212) of AIS patients showed an intrathecal IgG synthesis, 0.5% (1/212) with isolated elevated IgG index, 5.2% (7/136) isolated positive OCBs and 2.9% (4/136) both elevated IgG index and positive OCBs. CXCL13 levels were elevated in 3.6% (3/83) of the patients. Approximately one third of these patients had simultaneously chronic inflammatory CNS disease (multiple sclerosis, neuromyelitis optica spectrum disorder, neurosarcoidosis). There was no significant association between CSF findings and stroke characteristics including vascular territory, localization, volume, etiology, acute treatment, or blood-brain barrier dysfunction. Intrathecal IgG synthesis was more common in patients with prior stroke. Longitudinal CSF analysis did not reveal any newly-occurring, but instead mostly persistent or even disappearing intrathecal IgG synthesis after AIS. Conclusions: We found no evidence of a relevant B cell recruitment and intrathecal IgG synthesis in patients with AIS. In fact, the occurrence of intrathecal IgG synthesis was associated with concurrent chronic inflammatory CNS disease or previous stroke. Consequently, in patients with first-ever AIS and intrathecal IgG synthesis, physicians should search for concomitant inflammatory CNS disease. [ABSTRACT FROM AUTHOR]

The present study describes diagnostic and prognostic abilities of Cerebrospinal fluid (CSF) Pentraxin 3 (PTX3) in central nervous system (CNS) infections. CSF PTX3 was measured retrospectively from 174 patients admitted under suspicion of CNS infection. Medians, ROC curves and Youdens index was calculated. CSF PTX3 was significantly higher among all CNS infections and undetectable in most of the patients in the control group, and significantly higher in bacterial infections compared to viral and Lyme infections. No association was found between CSF PTX3 and Glasgow Outcome Score. PTX3 in the CSF can distinguish bacterial infection from viral and Lyme infections and non-CNS infections. Highest levels were found in bacterial meningitis. No prognostic abilities were found. [ABSTRACT FROM AUTHOR]

Objective: Doublecortin (DCX) and glypican-2 (GPC2) are neurodevelopmental proteins involved in the differentiation of neural stem/progenitor cells (NSPCs) to neurons, and are developmentally downregulated in neurons after birth. In this study, we investigated whether the concentrations of DCX and GPC2 in the cerebrospinal fluid (CSF) from human pediatric patients reflect this developmental process or are associated with cerebral damage or inflammatory markers. Methods: CSF was collected from pediatric patients requiring neurosurgical treatment. The concentrations of DCX, GPC2, neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B), and cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, IFN-γ, and TNF-⍺) were measured using immunoassays. Results: From March 2013 until October 2018, 63 CSF samples were collected from 38 pediatric patients (20 females; 17 patients with repeated measurements); the median term born-adjusted age was 3.27 years [Q1: 0.31, Q3: 7.72]. The median concentration of DCX was 329 pg/ml [Q1: 192.5, Q3: 1179.6] and that of GPC2 was 26 pg/ml [Q1: 13.25, Q3: 149.25]. DCX and GPC2 concentrations independently significantly associated with age, and their concentration declined with advancing age, reaching undetectable levels at 0.3 years for DCX, and plateauing at 1.5 years for GPC2. Both DCX and GPC2 associated with hydrocephalus, NSE, IL-1β, IL-2, IL-8, IL-13. No relationship was found between sex, acute infection, S100B, IL-4, IL-6, IL-10, IFN-γ, TNF-α and DCX or GPC2, respectively. Conclusions: Concentrations of DCX and GPC2 in the CSF from pediatric patients are developmentally downregulated, with the highest concentrations measured at the earliest adjusted age, and reflect a neurodevelopmental stage rather than a particular disease state. [ABSTRACT FROM AUTHOR]

Tryptophan (Trp) is an essential amino acid that functions in various biological processes and human daily health. As the significant functions of Trp become more apparent, its measurement is becoming increasingly important in various situations. Herein, we improved the Trp color reaction based on the Hopkins-Cole reaction and established a simple colorimetric method for Trp determination using several different reagents, including sodium hypochlorite pentahydrate and monosodium glutamate. The detection method can be performed using safe materials, rather than conventional toxic substances, and induces a crimson color change with an absorption peak at 525 nm, enabling the quantification of Trp by simple spectrophotometry in just 10 min. This assay exhibited a linear detection range from 10 to 100 mg/L (R2 = 0.9996). The average recoveries in the spiked cerebrospinal fluid ranged from 90.5% to 104.3%, with a relative standard deviation of 0.27% (n = 3, 29.40 mg/L Trp) to 1.19% (n = 3, 72.90 mg/L Trp). This novel spectrophotometric method may enable many researchers and laboratory technicians to detect Trp in various sample solutions without expensive analytical instruments or complicated operations. [ABSTRACT FROM AUTHOR]

Tau becomes abnormally hyper-phosphorylated and aggregated in tauopathies like Alzheimers disease (AD). As age is the greatest risk factor for developing AD, it is important to understand how tau protein itself, and the pathways implicated in its turnover, change during aging. We investigated age-related changes in total and phosphorylated tau in brain samples from two cohorts of cognitively normal individuals spanning 19–74 years, without overt neurodegeneration. One cohort utilised resected tissue and the other used post-mortem tissue. Total soluble tau levels declined with age in both cohorts. Phosphorylated tau was undetectable in the post-mortem tissue but was clearly evident in the resected tissue and did not undergo significant age-related change. To ascertain if the decline in soluble tau was correlated with age-related changes in autophagy, three markers of autophagy were tested but only two appeared to increase with age and the third was unchanged. This implies that in individuals who do not develop neurodegeneration, there is an age-related reduction in soluble tau which could potentially be due to age-related changes in autophagy. Thus, to explore how an age-related increase in autophagy might influence tau-mediated dysfunctions in vivo, autophagy was enhanced in a Drosophila model and all age-related tau phenotypes were significantly ameliorated. These data shed light on age-related physiological changes in proteins implicated in AD and highlights the need to study pathways that may be responsible for these changes. It also demonstrates the therapeutic potential of interventions that upregulate turnover of aggregate-prone proteins during aging. [ABSTRACT FROM AUTHOR]

Background: Meningoencephalitis of unknown origin (MUO) is an inflammatory disease of the canine central nervous system (CNS) that shares several features with multiple sclerosis (MS) in humans. In approximately 95% of MS patients, ≥ two immunoglobulin G (IgG) oligoclonal bands (OCBs) are detectable exclusively in the cerebrospinal fluid (CSF). Hypothesis/objectives: To investigate OCBs in CSF and serum in dogs affected by MUO, intervertebral disc disease (IVDD), idiopathic epilepsy (IE), intracranial neoplasia (IN), steroid-responsive meningitis-arteritis (SRMA), and diseases outside the CNS. We hypothesize that the highest prevalence of CSF-specific OCBs (≥ two OCBs uniquely in the CSF) would be found in dogs affected by MUO. Animals: Client-owned dogs (n = 121) presented to the neurology service due to neurological deficits. Methods: Prospective study. Measurement of IgG concentration in CSF and serum via a canine IgG ELISA kit. OCB detection via isoelectric focusing (IEF) and immunoblot. Results: Presence of CSF-specific OCBs was significantly higher in dogs with MUO (57%) compared to 22% in IN, 6% in IE, 15% in SRMA, 13% in IVDD, and 0% in the non-CNS group (p <.001). Dogs with MUO were 9.9 times more likely to show CSF-specific OCBs than all other diseases together (95% confidence interval, 3.7–26.4; p <.001). Conclusions and clinical importance: MUO showed the highest prevalence of CSF-specific OCBs, indicating an inflammatory B cell response. Future studies are needed to evaluate the prevalence in the specific MUO subtypes and a possible similarity with human MS. [ABSTRACT FROM AUTHOR]

Hydrocephalus is a neurological disease caused by an unusually high level of cerebrospinal fluid (CSF), which can be relieved by external ventricular drainage (EVD) insertion. However, the infection can lead to complications during the use of EVD. In this study, EVD was impregnated with three synergistic antibiotics, including rifampicin, clindamycin, and trimethoprim, to improve the antibacterial property. The impregnated drainage was studied for its characteristics in vitro and in vivo. Drug loading determination revealed that rifampicin had the highest concentration in the tube, followed by clindamycin and trimethoprim, respectively. In vitro cytotoxicity and hemolytic studies showed no toxic effects from antibiotics-impregnated EVD on fibroblast and red blood cells. For antibacterial testing, the impregnated EVD exhibited antibacterial activity against Staphylococcus aureus MRSA and Staphylococcus epidermidis up to 14 and 90 days, respectively. Moreover, biocompatibility and drug release into the bloodstream and surrounding tissues were investigated by implantation in rabbits for 30 days. Histology and morphology results showed that fibroblast cells began to adhere to the drainage surface and inflammatory cell numbers were noticeably small after the long-term implantation. In addition, there was no drug leakage to the bloodstream and surrounding tissues. Hence, this impregnated EVD can potentially be used for antibacterial application. [ABSTRACT FROM AUTHOR]

Patients with Parkinson's disease (PD) often suffer from sleep disturbances, including excessive daytime sleepiness (EDS) and rapid eye movement sleep behavior disorder (RBD). These symptoms are also experienced by patients with narcolepsy, which is characterized by orexin neuronal loss. In PD, a decrease in orexin neurons is observed pathologically, but the association between sleep disturbance in PD and cerebrospinal fluid (CSF) orexin levels is still unclear. This study aimed to clarify the role of orexin as a biomarker in patients with PD. CSF samples were obtained from a previous cohort study conducted between 2015 and 2020. We cross-sectionally and longitudinally examined the association between CSF orexin levels, sleep, and clinical characteristics. We analyzed 78 CSF samples from 58 patients with PD and 21 samples from controls. CSF orexin levels in patients with PD (median = 272.0 [interquartile range = 221.7–334.5] pg/mL) were lower than those in controls (352.2 [296.2–399.5] pg/mL, p = 0.007). There were no significant differences in CSF orexin levels according to EDS, RBD, or the use of dopamine agonists. Moreover, no significant correlation was observed between CSF orexin levels and clinical characteristics by multiple linear regression analysis. Furthermore, the longitudinal changes in orexin levels were also not correlated with clinical characteristics. This study showed decreased CSF orexin levels in patients with PD, but these levels did not show any correlation with any clinical characteristics. Our results suggest the limited efficacy of CSF orexin levels as a biomarker for PD, and that sleep disturbances may also be affected by dysfunction of the nervous system other than orexin, or by dopaminergic treatments in PD. Understanding the reciprocal role of orexin among other neurotransmitters may provide a better treatment strategy for sleep disturbance in patients with PD. [ABSTRACT FROM AUTHOR]

Background: Current diagnostics for patients with lingering symptoms categorized as post-treatment Lyme disease syndrome (PTLDS) have their limitations and may be difficult to interpret. The aim of this exploratory study was to evaluate the feasibility of protein biomarker profiling as a diagnostic platform for this category of patients and to compare these results with similarly obtained results from a group of patients with acute neuroborreliosis. Methods and findings: Two groups of patient cohorts (Cohort 1 and 2) were analyzed for biomarkers in serum and cerebrospinal fluid (CSF); the results were used for group-level comparison. Cohort 1 comprised 158 adult patients selected from 224 previously diagnosed patients, who between October 2015 and December 2018, after referral, were enrolled and structurally investigated based on defined inclusion criteria. They displayed similar lingering symptoms, with a duration of at least 6 months, after presumed previous tick-borne infection (TBI) and are fully described in a previously published study originating from the Center for Vector-borne Infections (CVI), Uppsala University Hospital, Sweden. Cohort 2, comprised 30 patients diagnosed at Uppsala University Hospital between 2016 and 2019 with laboratory-confirmed acute neuroborreliosis. Their proteomic results, based on serum and CSF analyses, were compared with the 158 patients in Cohort 1. The expression and the concentration of potential biomarkers in each patient's serum and CSF samples were measured based on two multiplex protein panels enabling simultaneous analysis of 92 inflammatory and neurology biomarkers. The PTLDS patient subgroup showed no nominally significant proteins compared to the other CVI patients in Cohort 1. However, CVI patients with signs of inflammation, which were evenly distributed in Cohort 1, showed 16 significantly (p <0.05) different proteins in both CSF and serum, but no association was seen with laboratory-confirmed exposure to Borrelia spp or other TBIs. When comparing the two cohorts, different protein profiles were observed, with 125/148 significantly different proteins in CSF and 93/174 in serum, in patients with laboratory confirmed acute neuroborreliosis, of which 6 in CSF and 6 in serum were significant at the p <0.001 level. Conclusions: In this first comprehensive inflammatory and neurological biomarker profile study no differences in biomarker profiles were detected between patients with PTLDS and patients with similar persisting symptoms but who did not meet the PTLDS criteria, regardless of whether laboratory verified previous exposure to Borrelia or other TBI's were present. However, the expressed markers differed from those found in patients with confirmed acute neuroborreliosis, which does not support the view that PTLDS reflects an ongoing Borrelia infection. Further studies are needed to understand and assess the usefulness of biosignatures of patients with PTLDS before they can be applied in a clinical setting. [ABSTRACT FROM AUTHOR]

Background: Recently, tau PET tracers have shown strong associations with clinical outcomes in individuals with cognitive impairment and cognitively unremarkable elderly individuals. flortaucipir PET scans to measure tau deposition in multiple brain areas as the disease progresses. This information needs to be summarized to evaluate disease severity and predict disease progression. We, therefore, sought to develop a machine learning-derived index, SPARE-Tau, which successfully detects pathology in the earliest disease stages and accurately predicts progression compared to a priori-based region of interest approaches (ROI). Methods: 587 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort had flortaucipir scans, structural MRI scans, and an Aβ biomarker test (CSF or florbetapir PET) performed on the same visit. We derived the SPARE-Tau index in a subset of 367 participants. We evaluated associations with clinical measures for CSF p-tau, SPARE-MRI, and flortaucipir PET indices (SPARE-Tau, meta-temporal, and average Braak ROIs). Bootstrapped multivariate adaptive regression splines linear regression analyzed the association between the biomarkers and baseline ADAS-Cog13 scores. Bootstrapped multivariate linear regression models evaluated associations with clinical diagnosis. Cox-hazards and mixed-effects models investigated clinical progression and longitudinal ADAS-Cog13 changes. The Aβ positive cognitively unremarkable participants, not included in the SPARE-Tau training, served as an independent validation group. Results: Compared to CSF p-tau, meta-temporal, and averaged Braak tau PET ROIs, SPARE-Tau showed the strongest association with baseline ADAS-cog13 scores and diagnosis. SPARE-Tau also presented the strongest association with clinical progression in cognitively unremarkable participants and longitudinal ADAS-Cog13 changes. Results were confirmed in the Aβ+ cognitively unremarkable hold-out sample participants. CSF p-tau showed the weakest cross-sectional associations and longitudinal prediction. Discussion: Flortaucipir indices showed the strongest clinical association among the studied biomarkers (flortaucipir, florbetapir, structural MRI, and CSF p-tau) and were predictive in the preclinical disease stages. Among the flortaucipir indices, the machine-learning derived SPARE-Tau index was the most sensitive clinical progression biomarker. The combination of different biomarker modalities better predicted cognitive performance. [ABSTRACT FROM AUTHOR]

Background: Neurofilament light chain (NfL) in cerebrospinal fluid (CSF) is a biomarker of multiple sclerosis (MS). However, CSF sampling is invasive and has limited the clinical application. With the development of highly sensitive single-molecule assay, the accurate quantification of the very low NfL levels in blood become feasible. As evidence being accumulated, we performed a meta-analysis to evaluate the diagnostic and predictive value of blood NfL in MS patients. Methods: We performed literature search on PubMed, EMBASE, Web of Science and Cochrane Library from inception to May 31, 2022. The blood NfL differences between MS vs. controls, MS vs. clinically isolated syndrome (CIS), progressive MS (PMS) vs. relapsing-remitting MS (RRMS), and MS in relapse vs. MS in remission were estimated by standard mean difference (SMD) and corresponding 95% confidence interval (CI). Pooled hazard ratio (HR) and 95%CI were calculated to predict time to reach Expanded Disability Status Scale (EDSS) score≥4.0 and to relapse. Results: A total of 28 studies comprising 6545 MS patients and 2477 controls were eligible for meta-analysis of diagnosis value, and 5 studies with 4444 patients were synthesized in analysis of predictive value. Blood NfL levels were significantly higher in MS patients vs. age-matched controls (SMD = 0.64, 95%CI 0.44–0.85, P<0.001), vs. non-matched controls (SMD = 0.76, 95%CI 0.56–0.96, P<0.001) and vs. CIS patients (SMD = 0.30, 95%CI 0.18–0.42, P<0.001), in PMS vs. RRMS (SMD = 0.56, 95%CI 0.27–0.85, P<0.001), and in relapsed patients vs. remitted patients (SMD = 0.54, 95%CI 0.16–0.92, P = 0.005). Patients with high blood NfL levels had shorter time to reach EDSS score≥4.0 (HR = 2.36, 95%CI 1.32–4.21, P = 0.004) but similar time to relapse (HR = 1.32, 95%CI 0.90–1.93, P = 0.155) compared to those with low NfL levels. Conclusion: As far as we know, this is the first meta-analysis evaluating the diagnosis and predictive value of blood NfL in MS. The present study indicates blood NfL may be a useful biomarker in diagnosing MS, distinguishing MS subtypes and predicting disease worsening in the future. [ABSTRACT FROM AUTHOR]

Background: Encephalitis is caused by autoimmune or infectious agents marked by brain inflammation. Investigations have reported altered concentrations of the cytokines in encephalitis. This study was conducted to determine the relationship between encephalitis and alterations of cytokine levels in cerebrospinal fluid (CSF) and serum. Methods: We found possibly suitable studies by searching PubMed, Embase, Scopus, and Web of Science, systematically from inception to August 2021. 23 articles were included in the meta-analysis. To investigate sources of heterogeneity, subgroup analysis and sensitivity analysis were conducted. The protocol of the study has been registered in PROSPERO with a registration ID of CRD42021289298. Results: A total of 23 met our eligibility criteria to be included in the meta-analysis. A total of 12 cytokines were included in the meta-analysis of CSF concentration. Moreover, 5 cytokines were also included in the serum/plasma concentration meta-analysis. According to the analyses, patients with encephalitis had higher CSF amounts of IL-6, IL-8, IL-10, CXCL10, and TNF-α than healthy controls. The alteration in the concentration of IL-2, IL-4, IL-17, CCL2, CXCL9, CXCL13, and IFN-γ was not significant. In addition, the serum/plasma levels of the TNF-α were increased in encephalitis patients, but serum/plasma concentration of the IL-6, IL-10, CXCL10, and CXCL13 remained unchanged. Conclusions: This meta-analysis provides evidence for higher CSF concentrations of IL-6, IL-8, IL-10, CXCL10, and TNF-α in encephalitis patients compared to controls. The diagnostic and prognostic value of these cytokines and chemokines should be investigated in future studies. [ABSTRACT FROM AUTHOR]

Objective: Tuberculous meningitis (TBM) is one of the most devastating TB. Accurate identification of TBM is helpful to eliminate TB. Therefore, we assessed the performance of TBAg stimulated IFN-γ (IGRA) and unstimulated IFN-γ in blood and cerebrospinal fluid (CSF) for diagnosing TBM. Methods: We searched Web of Science, PubMed, Embase and the Cochrane Library databases until March 2022. Bivariate and hierarchical summary receiver operating characteristic models were employed to compute summary estimates for diagnostic accuracy parameters of IGRA and unstimulated IFN-γ in blood and CSF for diagnosing TBM. Results: 28 studies including 1,978 participants and 2,641 samples met the inclusion criteria. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the curve (AUROC) of blood IGRA were separately as 0.73, 0.83, 4.32, 0.33, 13.22 and 0.86, indicating a good diagnostic accuracy of blood IGRA for detecting TBM. The summary sensitivity, specificity, PLR, NLR, DOR and AUROC of CSF IGRA were separately as 0.77, 0.91, 8.82, 0.25, 34.59 and 0.93, indicating good diagnostic accuracy of CSF IGRA for detecting TBM. The summary sensitivity, specificity, PLR, NLR, DOR and AUROC of CSF IFN-γ were separately as 0.86, 0.92, 10.27, 0.16, 65.26 and 0.95, suggesting CSF IFN-γ provided excellent accuracy for diagnosing TBM. Conclusions: For differentiating TBM from non-TBM individuals, blood and CSF IGRA are good assays and unstimulated CSF IFN-γ is an auxiliary excellent marker. [ABSTRACT FROM AUTHOR]

This protocol is a practical guide for preparing acute coronal slices from the midbrain of young adult mice for electrophysiology experiments. It describes two different sets of solutions with their respective incubation strategies and two alternative procedures for brain extraction: decapitation under terminal isoflurane anaesthesia and intracardial perfusion with artificial cerebrospinal fluid under terminal isoflurane anaesthesia. Slices can be prepared from wild-type mice as well as from mice that have been genetically modified or transfected with viral constructs to label subsets of cells. The preparation can be used to investigate the electrophysiological properties of midbrain neurons in combination with pharmacology, opto- and chemogenetic manipulations, and calcium imaging; which can be followed by morphological reconstruction, immunohistochemistry, or single-cell transcriptomics. The protocol also provides a detailed list of materials and reagents including the design for a low-cost and easy to assemble 3D printed slice recovery chamber, general advice for troubleshooting common issues leading to suboptimal slice quality, and some suggestions to ensure good maintenance of a patch-clamp rig. [ABSTRACT FROM AUTHOR]

Introduction: Lumbar puncture is among the investigations used to identify various neurological conditions, including some that can cause cardiac arrest (CA). However, CA per se may alter cerebrospinal fluid (CSF) characteristics. Few studies have investigated CSF findings after CA. In this descriptive work, we assessed the frequency and risk factors of abnormal CSF findings after CA and the contribution of CSF analysis to the etiological diagnosis. Materials and methods: We retrospectively studied data from prospectively established databases of consecutive patients who were admitted to two French ICUs in 2007–2016 with sustained return of spontaneous circulation (ROSC) after CA and who underwent lumbar puncture as an etiological investigation. Results: Of 1984 patients with sustained ROSC, 55 (2.7%) underwent lumbar puncture and were included. Lumbar puncture identified a neurological cause of CA in 2/55 (3.6%) patients. Nonspecific CSF abnormalities were noted in 37/53 (69.8%) patients. By multivariate analysis, postresuscitation shock was positively associated with CSF abnormalities (OR, 6.92; 95% confidence interval [95%CI], 1.62–37.26; P = 0.013). A no-flow time above 6 minutes (OR, 0.19; 95%CI, 0.03–1.11; P = 0.076) and a respiratory cause of CA (OR, 2.91; 95%CI, 0.53–23.15; P = 0.24) were not statistically associated with CSF abnormalities. Nonspecific CSF abnormalities were not significantly associated with poor outcomes (Cerebral Performance Category ≥3; P = 0.06). Conclusions: Lumbar puncture, although infrequently performed, may contribute to the etiological diagnosis of CA, albeit rarely. Nonspecific CSF abnormalities seem common after CA, notably with postresuscitation shock, and may be related to blood-brain barrier disruption. These findings may help to interpret CSF findings after CA. Further studies are warranted to assess our results. [ABSTRACT FROM AUTHOR]

Introduction: Cryptococcal meningitis (CM) is a life threatening disease and leading cause of opportunistic fungal-related mortality in HIV/AIDS. Most CM infections are caused by C. neoformans species complexes but the prevalence of Cryptococcus gattii species complexes in Uganda is unknown however, it is known in a few other parts of Africa. We estimated the prevalence of C. gattii in patients living with HIV and a diagnosis of cryptococcal meningitis in Uganda. Methods: Cryptococcus isolates (n = 200) obtained from cerebrospinal fluid of patients with CM recruited at the Infectious Diseases Institute, Kampala, Uganda, were tested by phenotypic methods. The Cryptococcus isolates were sub-cultured on Sabouraud Dextrose Agar plates for 48 hours. The yeast colonies were examined by India ink stain, urea hydrolysis, and C. gattii was identified by blue pigmentation on CGB agar. The results were analyzed for frequency of C. gattii. Patient demographic characteristics were collected from the case record forms. Results: From the 200 patients' case record forms, 87 (43.5%) were female and 113 (56.5%) were male. The median age was 35 (19–64) years. Most patients, 93% (187/200) were from Central Uganda in the districts of Kampala and Wakiso. 97.51% (157/161) of the patients had absolute CD4 lymphocyte counts of less than 200 cells per cubic millimeter; 1.86% (3/161) 200–350 cells per cubic millimeter and 0.62% (1/161) above 500 cells per cubic millimeter. 45.4% (74/163) were not yet on HAART and 54.6% (89/163) were on HAART. 66.7% (58/87) had poor adherence to HAART treatment and 33.3% (29/87) had reported good adherence to HAART treatment. A total of 200 clinical isolates of Cryptococcus isolates were tested. No (0% (0/200) C. gattii was identified among the Cryptococcus isolates. Conclusion: In this study among patients living with HIV and a diagnosis of cryptococcal meningitis in Uganda, we found no C. gattii infections. [ABSTRACT FROM AUTHOR]

Background: The possibility to better predict the severity of the disease in a patient newly diagnosed with multiple sclerosis would allow the treatment strategy to be personalized and lead to better clinical outcomes. Prognostic biomarkers are highly needed. Objective: To assess the prognostic value of intrathecal IgM synthesis, cerebrospinal fluid and serum IL-2, IL-6, IL-10, chitinase 3-like 2 and neurofilament heavy chains obtained early after the onset of the disease. Methods: 58 patients after the first manifestation of multiple sclerosis were included. After the initial diagnostic assessment including serum and cerebrospinal fluid biomarkers, all patients initiated therapy with either glatiramer acetate, teriflunomide, or interferon beta. To assess the evolution of the disease, we followed the patients clinically and with MRI for two years. Results: The IL-2:IL-6 ratio (both in cerebrospinal fluid) <0.48 (p = 0.0028), IL-2 in cerebrospinal fluid ≥1.23pg/ml (p = 0.026), and chitinase 3-like 2 in cerebrospinal fluid ≥7900pg/ml (p = 0.033), as well as baseline EDSS ≥1.5 (p = 0.0481) and age <22 (p = 0.0312), proved to be independent markers associated with shorter relapse free intervals. Conclusion: The IL-2:IL-6 ratio, IL-2, and chitinase 3-like 2 (all in cerebrospinal fluid) might be of value as prognostic biomarkers in early phases of multiple sclerosis. [ABSTRACT FROM AUTHOR]

Meningitis caused by Streptococcus pneumoniae is still a disease of great impact on Public health, which requires immediate diagnosis and treatment. However, the culture of clinical specimens is often negative and antibiotic susceptibility testing (AST) must be performed with isolated strains. Multiplex real-time polymerase chain reaction (qPCR) has high sensitivity and specificity, produces faster results to identify the pathogen, and it can also be an important tool to identify resistance antibiotic genes earlier than AST, especially in the absence of an isolated strain. This study developed a multiplex qPCR assay, using SYBR Green as a nonspecific dye, to detect antibiotic resistance genes to predict pneumococcal susceptibility/resistance in cerebrospinal fluid (CSF) samples from meningitis patients. From 2017 to 2020, CSF samples were cultured and analyzed by qPCR to detect the main three bacteria causing meningitis. Isolated and reference strains were applied in SYBR Green qPCR multiplex to detect pbp2b, ermB, and mef genes, and the results were compared with the AST. Pneumococcal-positive CSF samples (lytA-positive gene) without isolated strains were also tested to evaluate the antimicrobial susceptibility profile in the region from 2014 to 2020. From the received 873 CSF samples; 263 were cultivated, 149 were lytA-positive in the qPCR, and 25 produced viable isolated pneumococci strains, which were evaluated by AST. Melting temperature for each gene and the acceptance criteria were determined (pbp2b: 78.24–79.86; ermB: 80.88–82.56; mef: 74.85–76.34 ºC). A total of 48/51 strains presented a genetic profile in agreement with the AST results. Resistant strains to erythromycin and clindamycin were ermB-positive, and two were also mef-positive, indicating both resistance mechanisms were present. In the retrospective study of the genetic profile of resistance, 82 lytA-positive CSF samples plus 4 strains were applied in the SYBR Green qPCR multiplex: 51% of samples presented the wild genotype (pbp2b positive and ermB/mef negative); 15% were negative for all the three evaluated, indicating pneumococci resistant to penicillin; and 17% represented the multidrug-resistant pneumococci (pbp2b negative and ermB positive or pbp2b negative and ermB and mef positive). Therefore, SYBR Green qPCR multiplex proved to be a reliable tool to identify resistance genes in S. pneumoniae and would be less expensive than multiplex qPCR using specific probes. This could be easily introduced into the routine of diagnostic laboratories and provide a strong presumption of pneumococcal resistance, especially in the absence of isolated strains. [ABSTRACT FROM AUTHOR]

Tau protein is a key target of interest in developing therapeutics for neurodegenerative diseases. Here, we sought to develop a method that quantifies extracellular tau protein concentrations in human cerebrospinal fluid (CSF) without antibody-based enrichment strategies. We demonstrate that the fit-for-purpose validated method in Alzheimer's Disease CSF is limited to quasi quantitative measures of tau surrogate peptides. We also provide evidence that CSF total Tau measures by LC-MS are feasible in the presence of monoclonal therapeutic antibodies in human CSF. Our Tau LC-MS/MS method is a translational bioanalytical tool for assaying target engagement and pharmacodynamics for anti-tau antibody drug development campaigns. [ABSTRACT FROM AUTHOR]

Clinical and biochemical diversity of Parkinson's disease (PD) and numerous demographic, clinical, and pathological measures influencing cognitive function and its decline in PD create problems with the determination of effects of individual measures on cognition in PD. This is particularly the case where these measures significantly interrelate with each other producing intricate networks of direct and indirect effects on cognition. Here, we use generalized structural equation modelling (GSEM) to identify and characterize significant paths for direct and indirect effects of 14 baseline measures on global cognition in PD at baseline and at 4 years later. We consider 269 drug-naïve participants from the Parkinson's Progression Marker Initiative database, diagnosed with idiopathic PD and observed for at least 4 years after baseline. Two GSEM networks are derived, highlighting the possibility of at least two different molecular pathways or two different PD sub-types, with either CSF p-tau181 or amyloid beta (1–42) being the primary protein variables potentially driving progression of cognitive decline. The models provide insights into the interrelations between the 14 baseline variables, and determined their total effects on cognition in early PD. High CSF amyloid concentrations (> 500 pg/ml) are associated with nearly full protection against cognitive decline in early PD in the whole range of baseline age between 40 and 80 years, and irrespectively of whether p-tau181 or amyloid beta (1–42) are considered as the primary protein variables. The total effect of depression on cognition is shown to be strongly amplified by PD, but not at the time of diagnosis or at prodromal stages. CSF p-tau181 protein could not be a reliable indicator of cognitive decline because of its significantly heterogeneous effects on cognition. The outcomes will enable better understanding of the roles of the clinical and pathological measures and their mutual effects on cognition in early PD. [ABSTRACT FROM AUTHOR]

Background: The flow of physiologic fluids through organs and organs systems is an integral component of their function. The complex fluid dynamics in many organ systems are still not completely understood, and in-vivo measurements of flow rates and pressure provide a testament to the complexity of each flow system. Variability in in-vivo measurements and the lack of control over flow characteristics leave a lot to be desired for testing and evaluation of current modes of treatments as well as future innovations. In-vitro models are particularly ideal for studying neurological conditions such as hydrocephalus due to their complex pathophysiology and interactions with therapeutic measures. The following aims to present the reciprocating positive displacement pump, capable of inducing pulsating flow of a defined volume at a controlled beat rate and amplitude. While the other fluidic applications of the pump are currently under investigation, this study was focused on simulating the pulsating cerebrospinal fluid production across profiles with varying parameters. Methods: Pumps were manufactured using 3D printed and injection molded parts. The pumps were powered by an Arduino-based board and proprietary software that controls the linear motion of the pumps to achieve the specified output rate at the desired pulsation rate and amplitude. A range of 0.01 mlmin to 0.7 mlmin was tested to evaluate the versatility of the pumps. The accuracy and precision of the pumps' output were evaluated by obtaining a total of 150 one-minute weight measurements of degassed deionized water per output rate across 15 pump channels. In addition, nine experiments were performed to evaluate the pumps' control over pulsation rate and amplitude. Results: Volumetric analysis of a total of 1200 readings determined that the pumps achieved the target output volume rate with a mean absolute error of -0.001034283 mlmin across the specified domain. It was also determined that the pumps can maintain pulsatile flow at a user-specified beat rate and amplitude. Conclusion: The validation of this reciprocating positive displacement pump system allows for the future validation of novel designs to components used to treat hydrocephalus and other physiologic models involving pulsatile flow. Based on the promising results of these experiments at simulating pulsatile CSF flow, a benchtop model of human CSF production and distribution could be achieved through the incorporation of a chamber system and a compliance component. [ABSTRACT FROM AUTHOR]

Purpose: The recent developments of tau-positron emission tomography (tau-PET) enable in vivo assessment of neuropathological tau aggregates. Among the tau-specific tracers, the application of 11C-pyridinyl-butadienyl-benzothiazole 3 (11C-PBB3) in PET shows high sensitivity to Alzheimer disease (AD)-related tau deposition. The current study investigates the regional tau load in patients within the AD continuum, biomarker-negative individuals (BN) and patients with suspected non-AD pathophysiology (SNAP) using 11C-PBB3-PET. Materials and methods: A total of 23 memory clinic outpatients with recent decline of episodic memory were examined using 11C-PBB3-PET. Pittsburg compound B (11C-PIB) PET was available for 17, 18F-flurodeoxyglucose (18F-FDG) PET for 16, and cerebrospinal fluid (CSF) protein levels for 11 patients. CSF biomarkers were considered abnormal based on Aβ42 (< 600 ng/L) and t-tau (> 450 ng/L). The PET biomarkers were classified as positive or negative using statistical parametric mapping (SPM) analysis and visual assessment. Using the amyloid/tau/neurodegeneration (A/T/N) scheme, patients were grouped as within the AD continuum, SNAP, and BN based on amyloid and neurodegeneration status. The 11C-PBB3 load detected by PET was compared among the groups using both atlas-based and voxel-wise analyses. Results: Seven patients were identified as within the AD continuum, 10 SNAP and 6 BN. In voxel-wise analysis, significantly higher 11C-PBB3 binding was observed in the AD continuum group compared to the BN patients in the cingulate gyrus, tempo-parieto-occipital junction and frontal lobe. Compared to the SNAP group, patients within the AD continuum had a considerably increased 11C-PBB3 uptake in the posterior cingulate cortex. There was no significant difference between SNAP and BN groups. The atlas-based analysis supported the outcome of the voxel-wise quantification analysis. Conclusion: Our results suggest that 11C-PBB3-PET can effectively analyze regional tau load and has the potential to differentiate patients in the AD continuum group from the BN and SNAP group. [ABSTRACT FROM AUTHOR]

Background: The complexity of the inflammatory response post subarachnoid hemorrhage (SAH) may require temporal analysis of multiple protein biomarkers simultaneously to be more accurately described. Methods: Ventricular cerebrospinal fluid was collected at days 1, 4 and 10 after SAH in 29 patients. Levels of 92 inflammation-related proteins were simultaneously measured using Target 96 Inflammation ® assay (Olink Proteomics, Uppsala, Sweden) based on Proximity Extension Assay (PEA) technology. Twenty-eight proteins were excluded from further analysis due to lack of >50% of measurable values. Temporal patterns of the remaining 64 proteins were analyzed. Repeated measures ANOVA and its nonparametric equivalent Friedman's ANOVA were used for comparisons of means between time points. Results: Four different patterns (Groups A-D) were visually observed with an early peak and gradually decreasing trend (11 proteins), a middle peak (10 proteins), a late peak after a gradually increasing trend (30 proteins) and no specific pattern (13 proteins). Statistically significant early peaks defined as Day 1 > Day 4 values were noticed in 4 proteins; no significant decreasing trends defined as Day 1 > Day 4 > Day 10 values were observed. Two proteins showed significant middle peaks (i.e. Day 1 < Day 4 > Day 10 values). Statistically significant late peaks (i.e. Day 4 < Day 10 values) and increasing trends (i.e. Day 1 < Day 4 < Day 10 values) were observed in 14 and 10 proteins, respectively. Four of Group D proteins showed biphasic peaks and the rest showed stable levels during the observation period. Conclusion: The comprehensive data set provided in this explorative study may act as an illustration of an inflammatory profile of the acute phase of SAH showing groups of potential protein biomarkers with similar temporal patterns of activation, thus facilitating further research on their role in the pathophysiology of the disease. [ABSTRACT FROM AUTHOR]

This paper describes the effects of the interaction of cerebral fluids (arterial, capillary and venous blood, cerebrospinal fluid) on ventricular wall displacement and periventricular pressure using a mathematical multiphase poroelasticity model for the cerebral parenchyma. The interaction of cerebral fluids is given by a set of four numerical coefficients. A multiple linear regression with interaction is constructed that allows us to quantify the effect of these coefficients on the average ventricular wall displacement. The prevailing influence of an arterial-liquor component was observed. The sets of coefficients associated with such pathological conditions were found: normal pressure hydrocephalus, intracranial hypertension, and replacement ventriculomegaly under a prolonged hypoperfusion. [ABSTRACT FROM AUTHOR]

Low serum progranulin (PGRN) is known to be associated with granulin (GRN) gene mutation and T alleles of GRN rs5848 polymorphism. However, there have been only a few Asian studies exploring these. We investigated the serum PGRN levels, rs5848 genotypes, and their relations with cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers in the Korean population. Serum PGRN levels, GRN rs5848 polymorphism, and GRN mutations were evaluated in 239 participants (22 cognitively unimpaired participants and 217 patients with neurodegenerative diseases). CSF AD biomarkers were also evaluated in 214 participants. There was no significant difference in the serum PGRN levels among the diagnostic groups. We could not find any GRN mutation carrier in our sample. The differences in the frequencies of the rs5848 genotypes among the clinical groups or the effects of the rs5848 genotypes on serum PGRN were not observed. There was no correlation between the serum PGRN level or rs5848 genotype and CSF AD biomarkers. Neither the T allele nor the TT genotype had an effect on the development of AD. Our results showed that serum PGRN levels were not associated with rs5848 genotypes, indicating that multiple single nucleotide polymorphisms might affect PGRN concentrations in an ethnicity-specific manner. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have demonstrated that cytokines, transforming growth factor (TGF-β1), and brain-derived neurotrophic factor (BDNF) can impact the intensity of pain in rodents. However, the roles of cytokines, TGF-β1 and BDNF in humans with chronic pain in osteoarthritis remains unclear, and no comparison between plasma and central cerebral spinal fluid (CSF) has been conducted. Methods: Patients with osteoarthritis who were scheduled to receive spinal anesthesia were enrolled. The intensity of pain was evaluated with a visual analogue scale (VAS). In addition, patients with genitourinary system (GU) diseases and without obvious pain (VAS 0–1) were included as a comparison (control) group. The levels of TGF-β1, BDNF, tumor necrosis factor-α (TNF-α), and interleukin (IL)-8 within the CSF and plasma were collected and evaluated before surgery. Results: The plasma and CSF TGF-β1 levels were significantly lower in the osteoarthritis patients with pain (VAS ≥ 3) than in the GU control patients. Downregulation of plasma BDNF was also found in osteoarthritis patients with pain. The Spearman correlation analysis showed that the VAS pain scores were significantly negatively correlated with the levels of TGF-β1 in the CSF of patients with osteoarthritis. However, there was no significant correlations between the pain scores and the levels of BDNF, TNF-α, and IL-8 in either the CSF or plasma. Conclusions: TGF-β1 but not BDNF, TNF-α, or IL-8 may be an important biological indicator in the CSF of osteoarthritis patients with chronic pain. [ABSTRACT FROM AUTHOR]

Background: Canine idiopathic epilepsy (IE) is a common neurological disease with severe impact on the owner´s and the dog's quality of life. A subpopulation of dogs with IE does not respond to antiseizure drugs (non-responder). Th17 cells (T helper cells) and their proinflammatory Interleukin-17 (IL-17) are part of the immune system and previous studies showed their involvement in the pathogenesis of several autoimmune diseases. Non-responder might have an abnormal immune response against structures of the central nervous system. To discover a new aetiology of canine IE and thereby optimising the therapy of intractable IE, this prospective study aimed to investigate Th17 cells and IL-17 in dogs with IE. The underlying hypothesis was that in some dogs with IE a Th17 cell-mediated immune response could be detectable. Methods: 57 dogs with IE and 10 healthy dogs (control group, C) were enrolled in the study. EDTA blood was taken to measure Th17 cells by flow cytometry. IL-17 was measured in 35 cerebrospinal fluid (CSF) and 33 serum samples using an enzyme-linked immunosorbent assay (ELISA). It was investigated whether there was a significant increase of stimulated Th17 cells in blood samples or of IL-17 in serum and CSF samples of dogs with IE in comparison to C. Correlations between the amount of Th17 cells/μL or IL-17 and different clinical parameters e.g. seizure frequency, seizure type, seizure severity or treatment response were evaluated. Additionally, Th17 cells/μL were randomly controlled of 17 dogs with IE and were examined for changes over time and in relation to treatment response. Results: Ten dogs with IE had strongly elevated stimulated Th17 cells/μL within the blood (>100 Th17 cells/μL). A slight positive correlation between stimulated Th17 cells/μL and seizure severity (p = 0.046; rSpear = 0.27) was proven in these dogs. In addition, 4/10 dogs with elevated Th17 levels experienced cluster seizures and status epilepticus in comparison to 9% of the dogs with non-elevated Th17 levels (<100 Th17 cells/μL). Dogs with IE had significantly higher IL-17 values in CSF and serum samples compared to C (p<0.001; p<0.002; respectively). Conclusion: In single dogs with IE, strongly increased amounts of Th17 cells were detectable and dogs with elevated Th17 cells seemed to have a greater risk for experiencing a combination of cluster seizures and status epilepticus. Therefore, an underlying Th17-cell mediated immune response was suspected and hence anti-inflammatory drugs could be indicated in these single cases with intractable epilepsy. [ABSTRACT FROM AUTHOR]

Introduction: Cerebrospinal fluid (CSF) outflow has been demonstrated along nasal lymphatics via olfactory nerve projections; flow may be increased by stimulating lymphatic contractility using agents such as noradrenaline and the thromboxane A2 analog U46619. Lymphatics elsewhere in the body show increased contractility upon exposure to the prostaglandin F2alpha analog isoprostane-8-epi-prostaglandin. We investigated the ability of ophthalmic prostaglandin F2alpha analogs to increase CSF outflow when applied to the nasal mucosa by inhalation. Methods: Latanoprost (0.1, 0.5, or 1mg/ml), bimatoprost (0.3 or 3mg/ml), travoprost (0.04 or 0.4mg/ml), latanoprostene bunod (0.24 or 2.4mg/ml), tafluprost (0.25 or 2.5mg/ml), or control vehicle (10% DMSO) was administered to awake adult C57B/6 mice by nasal inhalation of 2μl droplets. Multiday dosing (daily for 3 days) of latanoprost also was evaluated. A total of 81 animals were studied including controls. General anesthesia was induced by injection, and fluorescent tracer (AlexaFluor647-labelled ovalbumin) was injected under stereotaxic guidance into the right lateral ventricle. Nasal turbinate tissue was harvested and homogenized after 1 hour for tracer detection by ELISA and fluorometric analysis. Results: Inhalation of latanoprost 0.5mg/ml and 1mg/ml led to a 11.5-fold increase in tracer recovery from nasal turbinate tissues compared to controls (3312 pg/ml vs 288 pg/ml, p<0.001 for 0.5mg/ml; 3355 pg/ml vs 288 pg/ml, p<0.001 for 1mg/ml), while latanoprost 0.1 mg/ml enhanced recovery 6-fold (1713 pg/ml vs 288 pg/ml, p<0.01). Tafluprost 0.25mg/ml and bimatoprost 0.3mg/ml showed a modest (1.4x, p<0.05) effect, and the remaining agents showed no significant effect on tracer recovery. After 3 days of daily latanoprost treatment and several hours after the last dose, a persistently increased recovery of tracer was found. Conclusions: Prostaglandin F2alpha analogs delivered by nasal inhalation resulted in increased nasal recovery of a CSF fluorescent tracer, implying increased CSF outflow via the nasal lymphatics. The greatest effect, partially dose-dependent, was observed using latanoprost. Further studies are needed to determine the efficacy of these agents in reducing ICP in short and long-term applications. [ABSTRACT FROM AUTHOR]

Objectives: We previously reported the diagnostic and prognostic performance of neurofilament light chain (NfL), TAR DNA-binding protein 43 (TDP-43), and total tau (t-tau) in cerebrospinal fluid (CSF) and plasma as amyotrophic lateral sclerosis (ALS) biomarkers. The present study aimed to elucidate associations between clinical characteristics and the markers as well as mutual associations of the markers in ALS patients using the same dataset. Methods: NfL, TDP-43, and t-tau levels in CSF and plasma in 75 ALS patients were analyzed. The associations between those markers and clinical details were investigated by uni- and multivariate analyses. Correlations between the markers were analyzed univariately. Results: In multivariate analysis of CSF proteins, the disease progression rate (DPR) was positively correlated with NfL (β: 0.51, p = 0.007) and t-tau (β: 0.37, p = 0.03). Plasma NfL was correlated with age (β: 0.53, p = 0.005) and diagnostic grade (β: -0.42, p = 0.02) in multivariate analysis. Plasma TDP-43 was correlated negatively with split hand index (β: -0.48, p = 0.04) and positively with % vital capacity (β: 0.64, p = 0.03) in multivariate analysis. Regarding mutual biomarker analysis, a negative correlation between CSF-NfL and TDP-43 was identified (r: -0.36, p = 0.002). Conclusions: Elevated NfL and t-tau levels in CSF may be biomarkers to predict rapid DPR from onset to sample collection. The negative relationship between CSF NfL and TDP-43 suggests that elevation of CSF TDP-43 in ALS is not a simple consequence of its release into CSF during neurodegeneration. The negative correlation between plasma TDP-43 and split hand index may support the pathophysiological association between plasma TDP-43 and ALS. [ABSTRACT FROM AUTHOR]

Background: Because of limited infrastructure and skilled human capital, the etiology of meningitis is rarely identified in developing countries like Ethiopia. This results in unnecessary antibiotics use, economic crisis, hospitalization, and related nosocomial infections. Thus, we aimed to assess the epidemiology of human enteroviruses (HEVs) among clinically suspected meningitis cases in Addis Ababa, Ethiopia. Method: A cross-sectional study was conducted from January to August 2020 at selected Hospitals in Addis Ababa, Ethiopia. Reverse transcriptase-polymerase chain reaction (RT-PCR) was conducted on cerebrospinal fluid (CSF) collected from 146 clinically suspected meningitis and bacterial culture-negative patients. SPSS v 21.0 was used for data analysis and bivariate correlation was done for the association between variables of interest. Results: HEVs were detected in 39 (26.7%) of the 146 clinically suspected meningitis cases. Most of the HEVs cases 28 (71.9%) were detected in younger-aged infants less than 1 year. The most commonly observed clinical manifestations were vomiting (75.5%) followed by fever (56.8%) and impaired consciousness or irritability (50.7%). The mean length of hospital stay for patients with enteroviral meningitis was 9 days. Many patients with HEVs were recovered with sequelae (46.2%), and HEVs has contributed for one out of the nine meningeal deaths (11.1%). Conclusions: HEVs were found to be the commonest cause of morbidity and mortality in all age groups. Many of the patients were mistreated with antibiotics and hospitalized. The detection of HEVs in 26.7% of clinically suspected meningitis cases indicated the need for molecular tests in investigating the etiology of meningitis. Therefore, we suggest the introduction of molecular tests as a routine practice in referral hospitals and the need to further characterize circulating HEVs strains. [ABSTRACT FROM AUTHOR]

Aim: Several pathophysiological processes are involved in Parkinson's disease (PD) and could inform in vivo biomarkers. We assessed an established biomarker panel, validated in Alzheimer's Disease, in a PD cohort. Methods: Longitudinal cerebrospinal fluid (CSF) samples from PPMI (252 PD, 115 healthy controls, HC) were analyzed at six timepoints (baseline, 6, 12, 24, 36, and 48 months follow-up) using Elecsys® electrochemiluminescence immunoassays to quantify neurofilament light chain (NfL), soluble TREM2 receptor (sTREM2), chitinase-3-like protein 1 (YKL40), glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), S100, and total α-synuclein (αSyn). Results: αSyn was significantly lower in PD (mean 103 pg/ml vs. HC: 127 pg/ml, p<0.01; area under the curve [AUC]: 0.64), while all other biomarkers were not significantly different (AUC NfL: 0.49, sTREM2: 0.54, YKL40: 0.57, GFAP: 0.55, IL-6: 0.53, S100: 0.54, p>0.05) and none showed a significant difference longitudinally. We found significantly higher levels of all these markers between PD patients who developed cognitive decline during follow-up, except for αSyn and IL-6. Conclusion: Except for αSyn, the additional biomarkers did not differentiate PD and HC, and none showed longitudinal differences, but most markers predict cognitive decline in PD during follow-up. [ABSTRACT FROM AUTHOR]

Brain aquaporin 1 (AQP1) and AQP4 are involved in cerebrospinal fluid (CSF) homeostasis and might participate in the origin of hydrocephalus. Studies have shown alterations of perivascular AQP4 expression in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD). Due to the overlapping of clinical signs between iNPH and certain neurological conditions, mainly AD, specific biomarkers might improve the diagnostic accuracy for iNPH. The goal of the present study was to analyze and quantify the presence of AQP1 and AQP4 in the CSF of patients with iNPH and AD to determine whether these proteins can be used as biomarkers of iNPH. We examined AQP1 and AQP4 protein levels in the CSF of 179 participants (88 women) classified into 5 groups: possible iNPH (81 participants), hydrocephalus associated with other neurological disorders (13 participants), AD (41 participants), non-AD dementia (32 participants) and healthy controls (12 participants). We recorded each participant's demographic and clinical variables and indicated, when available in the clinical history, the record of cardiovascular and respiratory complications. An ELISA showed virtually no AQP content in the CSF. Information on the vascular risk factors (available for 61 patients) confirmed some type of vascular risk factor in 86% of the patients with possible iNPH and 58% of the patients with AD. In conclusion, the ELISA analysis showed insufficient sensitivity to detect the presence of AQP1 and AQP4 in CSF, ruling out the possible use of these proteins as biomarkers for diagnosing iNPH. [ABSTRACT FROM AUTHOR]

Intervertebral disc herniation (IVDH) is a frequently occurring neurological disease of dogs and the most common reason for spinal cord injury (SCI). Clinical signs are variable thus a reliable prognosis is crucial for further treatment decisions. Currently, the prognosis of IVDH primarily depends on presence or absence of deep pain perception. The purpose of this study was to investigate if Th17-cells could serve as a potential, prognostic biomarker for IVDH. We investigated a possible role of the adaptive immune system in the pathophysiology of IVDH in dogs. The investigation was performed by analyzing the influence of Th17-cells in blood and cerebrospinal fluid (CSF) of sixty-two dogs suffering from IVDH. In addition, we examined if Th17-cells might influence the course of this disease. As controls, paired blood and CSF samples of ten healthy clinic-owned dogs were examined and the values were compared to those of the IVDH group. Isolated lymphocytes were analyzed after stimulation by using multicolour flow cytometry to measure the number of Th17-cells. IL-17 levels were measured in paired serum and CSF samples by Enzyme‐linked Immunosorbent Assays (ELISA). Highly significant differences of stimulated Th17-cells in EDTA-blood samples could be determined between Th17-cell levels of dogs suffering from IVDH and the healthy control group and also between three sampling time points: preoperative, after clinical improvement and after six months. Preoperatively, Th17-cell levels were strongly decreased in contrast to the healthy controls. The decreased amount of Th17-cell levels recovered postoperatively so that Th17-cell levels of the last follow-up examinations were comparable to the control group after six months. At the same time IL-17 measured in serum preoperatively was significantly higher in dogs with IVDH than in healthy controls. However, there was no considerable difference of IL-17 measured in CSF between the groups. In conclusion, a high activity and consequent consumption of IL-17-producing Th17-cells is suspected in acute IVDH. These findings may indicate an involvement of Th17-cells in the pathogenesis of IVDH and emphasize that these cells might be involved in the interaction of pain, stress and immune reaction. However, based on the findings of this study the development of Th17-cells as a biomarker cannot be recommended, yet. [ABSTRACT FROM AUTHOR]

Background: Though many previous studies have indicated immunological alterations in psychotic disorders, the role and prevalence of neuroinflammation is still unknown. Studies previously investigating immune related biomarkers in the cerebrospinal fluid (CSF) of these patients are mainly small studies on few markers, and many have not compared patients to healthy controls. Methods: We will conduct a large case-control study including at least 100 patients with recent onset psychotic disorders and 100 sex- and age matched healthy controls. The cases will include patients diagnosed with a psychotic disorder according to ICD-10 (F20/F22-29) within a year prior to inclusion. We will collect both CSF, blood and fecal samples, to gain insight into possible immunological alterations. The psychopathology of all participants will thoroughly be evaluated using the SCAN interview, and multiple rating scales covering different symptom groups. All participants will partake in a detailed neurological examination, including the Neurological Evaluation Scale assessing neurological soft signs. Additionally, we will assess cognitive functioning, evaluate quality of life and level of functioning, and collect data on a broad array of possible confounders. Our primary outcomes will include CSF leucocytes, CSF/serum albumin ratio, CSF total protein, IgG index, CSF levels of IL-6 and IL-8, and presence of antineuronal autoantibodies in CSF and blood. For our secondary outcomes, exploratory analyses will be performed on a broader panel of neuroimmunological markers. All participants will be invited for a follow-up visit to assess longitudinal changes. The current study is part of a larger CSF biobank build-up for severe mental disorders (PSYCH-FLAME). Discussion: This study will represent the largest investigation of CSF in patients with psychotic disorders compared to healthy controls to date. We expect the study to contribute with new, important knowledge on pathophysiological mechanisms, and to help pave the way for future investigations of individualized treatment options. Trial registration: The study is approved by The Regional Committee on Health Research Ethics (Capital Region, j.no: H-16030985) and The Danish Data Protection Agency (j.no: RHP-2016-020, I-Suite no.: 04945). [ABSTRACT FROM AUTHOR]

Background: With the widespread use of broad-spectrum antibiotics, the problem of bacterial resistance has become a global crisis. To monitor bacterial resistance in our hospital, the distribution of specimens, the detection of pathogens and their drug resistance from July 2005 to June 2007 (13 years ago) and July 2018 to June 2020 were compared and analyzed. Methods: Ordinary specimens (such as sputum, urine, feces, and secretion) were inoculated in blood AGAR media, MacConkey medium, chocolate medium, double SS medium and selective culture medium. Blood, cerebrospinal fluid, pleural effusion, joint cavity effusion and other sterile body fluid samples were inoculated in aerobic and anaerobic blood culture flasks. Automatic microbial identification, drug sensitivity analysis and mass spectrometry analysis were used to determine their drug sensitivity. Results: Compared with the results obtained 13 years ago, the number of specimens submitted for inspection in the past two years has increased significantly, exhibiting a growth rate of 283%. The changes in the pathogen species were obvious. Gram-positive cocci were the dominant bacteria 13 years ago, and Gram-negative bacilli were the dominant bacteria in the past two years. In addition, the resistance of several major Gram-negative bacilli to piperacillin/tazobactam, cefoperazone/sulbactam, meropenem and imipenem all showed an increasing trend. Conclusion: The variety of pathogenic bacteria in our hospital has changed significantly in the past two years compared with that 13 years ago, and the clinical isolates of Gram-negative bacilli have increased significantly compared with Gram-positive cocci. In the clinical treatment of anti-infective diseases, antimicrobial agents should be selected according to the bacterial distribution characteristics and drug resistance in each hospital. [ABSTRACT FROM AUTHOR]

We hypothesized that automated assessment of brain volumes on MRI can predict presence of cerebrospinal fluid abnormal ß-amyloid42 and Tau protein levels and thus serve as a useful screening test for possible Alzheimer's disease. 113 participants ranging from cognitively healthy to Alzheimer's disease underwent MRI exams to obtain measurements of hippocampus, prefrontal cortex, precuneus, parietal cortex, and occipital lobe volumes. A non-exclusive subset (n = 107) consented to lumbar punctures to obtain cerebrospinal fluid for ß-amyloid42 and Tau protein assessment including cognitively health (n = 75), mild cognitively impaired (n = 22), and Alzheimer's disease (n = 10). After adjustment for false discovery rate, ß-amyloid42 was significantly associated with volumes in the hippocampus (p = 0.043), prefrontal cortex (p = 0.010), precuneus (p = 0.024), and the posterior cingulate (p = 0.002). No association between Tau levels and regional brain volume survived multiple test correction. Secondary analysis was performed to determine associations between MRI brain volumes and CSF protein levels to neuropsychological impairment. A non-exclusive subset (n = 96) including cognitively healthy (n = 72), mild cognitively impaired (n = 21), and Alzheimer's disease (n = 3) participants underwent Stroop Interference and Boston Naming neuropsychological testing. A higher score on the Boston Naming Test was optimally predicted in a selective regression model by greater hippocampus volume (p = 0.002), a higher ratio of ß-amyloid42 to Tau protein levels (p < 0.001), greater posterior cingulate volume (p = 0.0193), age (p = 0.0271), and a higher education level (p = 0.002). A better performance on the Stroop Interference Test was optimally predicted by greater hippocampus volume (p = 0.0003) and a higher education level (p < 0.001). Lastly, impaired cognitive status (mild cognitive impairment and Alzheimer's Disease) was optimally predicted in a selective regression model by a worse performance on the Stroop Interference Test (p < 0.001), a worse performance on the Boston Naming Test (p < 0.001), along with lower prefrontal cortex volume (p = 0.002) and lower hippocampus volume (p = 0.007). [ABSTRACT FROM AUTHOR]

BackgroundMeasurement of HIV DNA-bearing cells in cerebrospinal fluid (CSF) is challenging because few cells are present. We present a novel application of the sensitive droplet digital (dd)PCR in this context.MethodsWe analyzed CSF cell pellets and paired peripheral blood mononuclear cells (PBMC) from 28 subjects, 19 of whom had undetectable HIV RNA (