Specimen type validation and establishment of normal cytokine reference intervals in cerebrospinal fluid.

Cerebrospinal fluid (CSF) is a critical body fluid to examine in attempts to discover potential biomarkers for neuroinflammatory and other disorders of the central nervous system (CNS). Serum and/or plasma cytokine levels have been associated with a variety of inflammatory conditions, and some have been shown to be actionable therapeutic targets. Less is known, however, about cytokine levels in CSF. Serum and plasma cytokine testing is widely available in clinical and research laboratories, but cytokine testing in CSF is extremely limited and if performed, accompanied by a disclaimer that it is an unvalidated specimen type. In this study, we validate CSF as a suitable specimen type and determine normal reference intervals for multiple cytokines as well as a soluble cytokine receptor. CSF was validated as a specimen type for testing using a laboratory developed multiplexed cytokine assay previously validated to measure 13 cytokines/markers in serum and plasma. Performance parameters including specimen dilution, specimen interference, linearity and precision were examined. Reference intervals were established using 197 normal and control CSF specimens by non-parametric quantile-based methods. CSF cytokine analysis demonstrated within and between run precision of <10% and < 20% CV, respectively and linearity of ±15% for all analytes throughout the analytical measurement range of the assay. Reference intervals for the 13 cytokines/markers were established from 197 normal and control CSF specimens (78 Male; mean 44.8 y ± 21.7 SD, 119 Female; mean 42.8 y ± 20.3 SD). Cytokine concentrations in CSF from normal donors and controls were less than the lower limit of quantitation of our assay for 6 of the 13 measured cytokines/markers. The chemokine IL8 demonstrated the highest concentration of all analytes measured. CSF demonstrated acceptable performance as a specimen type in our multiplexed cytokine assay. By validating CSF as a specimen type and establishing normal reference intervals for cytokine concentrations in CSF, their potential as biomarkers for infectious, autoimmune and other inflammatory CNS disorders can be more appropriately investigated.

CAIDE Score, Alzheimer's Disease Pathology, and Cognition in Cognitively Normal Adults: The CABLE Study.

Background: Cardiovascular Risk Factors, Ageing and Dementia (CAIDE) risk score serves as a credible predictor of an individual's risk of dementia. However, studies on the link of the CAIDE score to Alzheimer's disease (AD) pathology are scarce. Objective: To explore the links of CAIDE score to cerebrospinal fluid (CSF) biomarkers of AD as well as to cognitive performance. Methods: In the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study, we recruited 600 cognitively normal participants. Correlations between the CAIDE score and CSF biomarkers of AD as well as cognitive performance were probed through multiple linear regression models. Whether the correlation between CAIDE score and cognitive performance was mediated by AD pathology was researched by means of mediation analyses. Results: Linear regression analyses illustrated that CAIDE score was positively associated with tau-related biomarkers, including pTau (p <  0.001), tTau (p <  0.001), as well as tTau/Aß42 (p = 0.008), while it was in negative association with cognitive scores, consisting of MMSE score (p <  0.001) as well as MoCA score (p <  0.001). The correlation from CAIDE score to cognitive scores was in part mediated by tau pathology, with a mediation rate varying from 3.2% to 13.2% . Conclusions: A higher CAIDE score, as demonstrated in our study, was linked to more severe tau pathology and poorer cognitive performance, and tau pathology mediated the link of CAIDE score to cognitive performance. Increased dementia risk will lead to cognitive decline through aggravating neurodegeneration.

Cerebrospinal fluid synaptic biomarker changes in bipolar disorder - A longitudinal case-control study.

BACKGROUND: This exploratory study investigated cerebrospinal fluid (CSF) synaptic protein biomarkers in bipolar disorder (BD), aiming to highlight the neurobiological basis of the disorder. With shared cognitive impairment features between BD and Alzheimer's disease, and considering increased dementia risk in BD patients, the study explores potential connections. METHODS: Fifty-nine well-characterized patients with BD and thirty-seven healthy control individuals were examined and followed for one year. Synaptic proteins encompassing neuronal pentraxins (NPTX)1, NPTX2, and NPTX-receptor, 14-3-3 protein family epsilon, and zeta/delta, activating protein-2 complex subunit beta, synucleins beta-synuclein and gamma-synuclein, complexin-2, phosphatidylethanolamine-binding protein 1, rab GDP dissociation inhibitor alpha, and syntaxins 1B and 7 were measured in CSF using a microflow liquid chromatography-mass spectrometric multiple reaction monitoring set-up. Biomarker levels were compared between BD and HC and in BD before, during, and after mood episodes. RESULTS: The synaptic proteins revealed no statistically significant differences between BD and HC, neither at baseline, one-year follow-up, or in terms of changes from baseline to follow-up. Moreover, the CSF synaptic protein levels in patients with BD were unaltered compared to baseline when they stabilized in euthymia following an affective episode and at one-year follow-up. LIMITATION: It is uncertain what the CSF biomarker concentrations reflect since we yet do not know the mechanisms of release of these proteins, and we are uncertain of what increased or decreased levels reflect. CONCLUSION: This first-ever investigation of a panel of CSF protein biomarkers of synaptic dysfunction in patients with BD and HC individuals found no statistically significant differences cross-sectionally or longitudinally.

Assessment of the Correlation and Diagnostic Accuracy between Cerebrospinal Fluid and Plasma Alzheimer's Disease Biomarkers: A Comparison of the Lumipulse and Simoa Platforms.

We compared the clinical and analytical performance of Alzheimer's disease (AD) plasma biomarkers measured using the single-molecule array (Simoa) and Lumipulse platforms. We quantified the plasma levels of amyloid beta 42 (Aß42), Aß40, phosphorylated tau (Ptau181), and total tau biomarkers in 81 patients with mild cognitive impairment (MCI), 30 with AD, and 16 with non-AD dementia. We found a strong correlation between the Simoa and Lumipulse methods. Concerning the clinical diagnosis, Simoa Ptau181/Aß42 (AUC 0.739, 95% CI 0.592-0.887) and Lumipulse Aß42 and Ptau181/Aß42 (AUC 0.735, 95% CI 0.589-0.882 and AUC 0.733, 95% CI 0.567-0.900) had the highest discriminating power. However, their power was significantly lower than that of CSF Aß42/Aß40, as measured by Lumipulse (AUC 0.879, 95% CI 0.766-0.992). Simoa Ptau181 and Lumipulse Ptau181/Aß42 were the markers most consistent with the CSF Aß42/Aß40 status (AUC 0.801, 95% CI 0.712-0.890 vs. AUC 0.870, 95% CI 0.806-0.934, respectively) at the ≥2.127 and ≥0.084 cut-offs, respectively. The performance of the Simoa and Lumipulse plasma AD assays is weaker than that of CSF AD biomarkers. At present, the analysed AD plasma biomarkers may be useful for screening to reduce the number of lumbar punctures in the clinical setting.

Unlocking Preclinical Alzheimer's: A Multi-Year Label-Free In Vitro Raman Spectroscopy Study Empowered by Chemometrics.

Alzheimer's disease is a progressive neurodegenerative disorder, the early detection of which is crucial for timely intervention and enrollment in clinical trials. However, the preclinical diagnosis of Alzheimer's encounters difficulties with gold-standard methods. The current definitive diagnosis of Alzheimer's still relies on expensive instrumentation and post-mortem histological examinations. Here, we explore label-free Raman spectroscopy with machine learning as an alternative to preclinical Alzheimer's diagnosis. A special feature of this study is the inclusion of patient samples from different cohorts, sampled and measured in different years. To develop reliable classification models, partial least squares discriminant analysis in combination with variable selection methods identified discriminative molecules, including nucleic acids, amino acids, proteins, and carbohydrates such as taurine/hypotaurine and guanine, when applied to Raman spectra taken from dried samples of cerebrospinal fluid. The robustness of the model is remarkable, as the discriminative molecules could be identified in different cohorts and years. A unified model notably classifies preclinical Alzheimer's, which is particularly surprising because of Raman spectroscopy's high sensitivity regarding different measurement conditions. The presented results demonstrate the capability of Raman spectroscopy to detect preclinical Alzheimer's disease for the first time and offer invaluable opportunities for future clinical applications and diagnostic methods.

Pharmacologic Venous Thromboembolism Prophylaxis in Patients with Nontraumatic Subarachnoid Hemorrhage Requiring an External Ventricular Drain.

BACKGROUND: Optimal pharmacologic thromboprophylaxis dosing is not well described in patients with subarachnoid hemorrhage (SAH) with an external ventricular drain (EVD). Our patients with SAH with an EVD who receive prophylactic enoxaparin are routinely monitored using timed anti-Xa levels. Our primary study goal was to determine the frequency of venous thromboembolism (VTE) and secondary intracranial hemorrhage (ICH) for this population of patients who received pharmacologic prophylaxis with enoxaparin or unfractionated heparin (UFH). METHODS: A retrospective chart review was performed for all patients with SAH admitted to the neurocritical care unit at Emory University Hospital between 2012 and 2017. All patients with SAH who required an EVD were included. RESULTS: Of 1,351 patients screened, 868 required an EVD. Of these 868 patients, 627 received enoxaparin, 114 received UFH, and 127 did not receive pharmacologic prophylaxis. VTE occurred in 7.5% of patients in the enoxaparin group, 4.4% in the UFH group (p = 0.32), and 3.2% in the no VTE prophylaxis group (p = 0.08). Secondary ICH occurred in 3.83% of patients in the enoxaparin group, 3.51% in the UFH group (p = 1), and 3.94% in the no VTE prophylaxis group (p = 0.53). As steady-state anti-Xa levels increased from 0.1 units/mL to > 0.3 units/mL, there was a trend toward a lower incidence of VTE. However, no correlation was noted between rising anti-Xa levels and an increased incidence of secondary ICH. When compared, neither enoxaparin nor UFH use was associated with a significantly reduced incidence of VTE or an increased incidence of ICH. CONCLUSIONS: In this retrospective study of patients with nontraumatic SAH with an EVD who received enoxaparin or UFH VTE prophylaxis or no VTE prophylaxis, there was no statistically significant difference in the incidence of VTE or secondary ICH. For patients receiving prophylactic enoxaparin, achieving higher steady-state target anti-Xa levels may be associated with a lower incidence of VTE without increasing the risk of secondary ICH.

Proximity extension assay in cerebrospinal fluid identifies neurofilament light chain as biomarker of neurodegeneration in sporadic cerebral amyloid angiopathy.

BACKGROUND: Sporadic cerebral amyloid angiopathy (sCAA) is a disease characterised by the progressive deposition of the amyloid beta (Aß) in the cerebral vasculature, capable of causing a variety of symptoms, from (mild) cognitive impairment, to micro- and major haemorrhagic lesions. Modern diagnosis of sCAA relies on radiological detection of late-stage hallmarks of disease, complicating early diagnosis and potential interventions in disease progression. Our goal in this study was to identify and validate novel biomarkers for sCAA. METHODS: We performed a proximity extension assay (PEA) on cerebrospinal fluid (CSF) samples of sCAA/control participants (n = 34/51). Additionally, we attempted to validate the top candidate biomarker in CSF and serum samples (n = 38/26) in a largely overlapping validation cohort, through analysis with a targeted immunoassay. RESULTS: Thirteen proteins were differentially expressed through PEA, with top candidate NFL significantly increased in CSF of sCAA patients (p < 0.0001). Validation analyses using immunoassays revealed increased CSF and serum NFL levels in sCAA patients (both p < 0.0001) with good discrimination between sCAA and controls (AUC: 0.85; AUC: 0.79 respectively). Additionally, the CSF: serum NFL ratio was significantly elevated in sCAA (p = 0.002). DISCUSSION: Large-scale targeted proteomics screening of CSF of sCAA patients and controls identified thirteen biomarker candidates for sCAA. Orthogonal validation of NFL identified NFL in CSF and serum as biomarker, capable of differentiating between sCAA patients and controls.

Prognostic Factors for Japanese Adults With Acute Community-Acquired Bacterial Meningitis: A Retrospective Study.

Background This study aimed to determine if the cerebrospinal fluid (CSF) cell count is useful for predicting the infection severity or prognosis in Japanese adults with community-acquired bacterial meningitis. Methodology This study retrospectively evaluated the prognosis of patients diagnosed with community-acquired bacterial meningitis at our hospital from January 2004 to December 2021 using the modified Rankin scale (mRs) (Showa General Hospital; N = 39). Patients were classified into the following two groups: (i) favorable (mRs: 0-3) and (ii) unfavorable (mRs: 4-6). Eight factors were selected and compared with outcomes, and then two factors were evaluated from those, and a multivariate logistic regression was used to determine the significant variables. Results CSF cell count was observed to be associated with poor prognoses (odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.99995-0.99999, p = 0.0012). Glasgow coma scale (GCS) score on admission was also observed to be associated with poor prognoses (OR = 0.93, 95% CI = 0.89145-0.97290, p = 0.0029). Conclusions Low CSF cell count and low GCS on admission were observed as risk factors for poor prognoses in patients with bacterial meningitis.

Case report: Chronic Candida albicans meningitis: a rare entity diagnosed by metagenomic next-generation sequencing.

The aetiology of chronic aseptic meningitis is difficult to establish. Candida meningitis in particular is often diagnosed late, as cerebrospinal fluid (CSF) work-up and imaging findings are nonspecific. A 35-year-old patient with chronic aseptic meningitis, for which repeated microbiological testing of CSF was unrevealing, was finally diagnosed with Candida albicans (C. albicans) meningitis with cauda equina involvement using metagenomic next-generation sequencing (mNGS). This report highlights the diagnostic challenges and the difficulties of treating shunt-associated fungal meningitis.

Evaluation of clinical predictors of postoperative outcomes in tegmen defect patients with and without concurrent superior semicircular canal dehiscence and cerebrospinal fluid leak.

OBJECTIVES: Tegmen and superior semicircular canal defects have been well studied, yet the factors contributing to their onset and progression are widely debated. The clinical utility of intraoperative intracranial pressure measurements has yet to be tested. This report aims to use intraoperative opening pressure and concurrent superior semicircular canal dehiscence (SSCD) to analyze factors influencing disease course and clinical outcomes in patients with tegmen dehiscence. METHODS: A retrospective analysis of 61 patients who underwent tegmen defect repair was performed. Multiple variables of interest including body mass index (BMI), presence of SSCD, presence of dural venous sinus stenosis, opening pressure, and acetazolamide therapy use were recorded. The cohort was divided into those with or without concurrent SSCD and those presenting with or without cerebrospinal fluid (CSF) leak for analysis. RESULTS: A linear relationship between opening pressure and BMI (p = 0.009) was noted; however, intraoperative opening pressure was not associated with disease outcome. Concurrent SSCD was present in 25 % of patients, while 62 % presented with CSF leak. The concurrent SSCD group exhibited higher opening pressure, higher likelihood of having dural sinus stenosis, and higher likelihood of being discharged on acetazolamide. The CSF leak group had higher likelihood of obstructive sleep apnea and persistent symptoms. CONCLUSIONS: In patients undergoing tegmen defect repair, concurrent SSCD suggests increased disease severity. The presence of preoperative CSF leak predicts persistent symptoms following repair. BMI is linearly correlated with intracranial pressure in these patients.

Risk Factors Associated with Postoperative Cerebrospinal Fluid Leaks After Intrathecal Drug Delivery System and an External Pump Implantation in Cancer Patients: A Retrospective Study.

INTRODUCTION: To determine risk factors associated with postoperative cerebrospinal fluid leaks (CSFLs) after intrathecal drug delivery system (IDDS) and external pump implantation. METHODS: The clinical data of 248 patients with advanced cancer who underwent IDDS implantation from January 2021 to December 2022 at the Department of Pain Medicine at the Hunan Cancer Hospital were retrospectively reviewed. Information regarding age, gender, height, weight, body mass index (BMI), tumour type, albumin levels, haemoglobin levels, history of diabetes and pre- and postoperative anti-tumour therapy was collected and analysed. RESULTS: Postoperative CSFLs occurred in 7 of 231 patients (3.30%). Statistical analysis indicated that gender, age, height, weight, BMI, tumour type, albumin levels, haemoglobin levels, history of diabetes, pre- and postoperative chemotherapy, pre- and postoperative radiotherapy, preoperative immunotherapy and postoperative targeted therapy were not independent factors for CSFLs. Preoperative targeted therapy [odds ratio (OR): 16.64; 95% confidence interval (CI): 1.42, 195.56; P = 0.01] and postoperative immunotherapy (OR: 13.38; 95% CI: 1.60, 111.65; P = 0.017) were factors associated with an increased postoperative CSFL rate. Of the two locations where CSFLs can occur, the back (puncture site of catheter, n = 4) and the hypochondriac region (location of infusion port implanted, n = 3), back CSFLs occurred earlier than in the hypochondriac region (18.25 ± 6.45 vs 115 ± 62.02 days, P = 0.032). CONCLUSION: Based on the data from our study, the timing of preoperative targeted therapy and postoperative immunotherapy should be considered to prevent the occurrence of CSFLs in cancer pain patients who have an IDDS and external pump.

A Case of Ketorolac-Induced Aseptic Meningitis.

Drug-induced aseptic meningitis is a rare condition that occurs because of an adverse reaction to medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Unlike bacterial or viral meningitis, aseptic meningitis is not caused by an infection, but rather by an inflammatory response. This condition creates a challenge since patients with aseptic meningitis often present with classic clinical meningeal symptoms, including fever, headache, and neck stiffness. We present a case of a patient with NSAID-induced aseptic meningitis and highlight the importance for healthcare providers to have a high index of suspicion for drug-induced aseptic meningitis in patients presenting with symptoms of meningitis with negative cerebrospinal fluid analysis and culture.

Single-cell transcriptome reveals highly complement activated microglia cells in association with pediatric tuberculous meningitis.

Background: Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB) causing high mortality and disability. TBM arises due to immune dysregulation, but the underlying immune mechanisms are unclear. Methods: We performed single-cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid (CSF) cells isolated from children (n=6) with TBM using 10 xGenomics platform. We used unsupervised clustering of cells and cluster visualization based on the gene expression profiles, and validated the protein and cytokines by ELISA analysis. Results: We revealed for the first time 33 monocyte populations across the CSF cells and PBMCs of children with TBM. Within these populations, we saw that CD4_C04 cells with Th17 and Th1 phenotypes and Macro_C01 cells with a microglia phenotype, were enriched in the CSF. Lineage tracking analysis of monocyte populations revealed myeloid cell populations, as well as subsets of CD4 and CD8 T-cell populations with distinct effector functions. Importantly, we discovered that complement-activated microglial Macro_C01 cells are associated with a neuroinflammatory response that leads to persistent meningitis. Consistently, we saw an increase in complement protein (C1Q), inflammatory markers (CRP) and inflammatory factor (TNF-α and IL-6) in CSF cells but not blood. Finally, we inferred that Macro_C01 cells recruit CD4_C04 cells through CXCL16/CXCR6. Discussion: We proposed that the microglial Macro_C01 subset activates complement and interacts with the CD4_C04 cell subset to amplify inflammatory signals, which could potentially contribute to augment inflammatory signals, resulting in hyperinflammation and an immune response elicited by Mtb-infected tissues.

1H-NMR metabolomics investigation of CSF from children with HIV reveals altered neuroenergetics due to persistent immune activation.

Background: HIV can invade the central nervous system (CNS) early during infection, invading perivascular macrophages and microglia, which, in turn, release viral particles and immune mediators that dysregulate all brain cell types. Consequently, children living with HIV often present with neurodevelopmental delays. Methods: In this study, we used proton nuclear magnetic resonance (1H-NMR) spectroscopy to analyze the neurometabolic profile of HIV infection using cerebrospinal fluid samples obtained from 17 HIV+ and 50 HIV- South African children. Results: Nine metabolites, including glucose, lactate, glutamine, 1,2-propanediol, acetone, 3-hydroxybutyrate, acetoacetate, 2-hydroxybutyrate, and myo-inositol, showed significant differences when comparing children infected with HIV and those uninfected. These metabolites may be associated with activation of the innate immune response and disruption of neuroenergetics pathways. Conclusion: These results elucidate the neurometabolic state of children infected with HIV, including upregulation of glycolysis, dysregulation of ketone body metabolism, and elevated reactive oxygen species production. Furthermore, we hypothesize that neuroinflammation alters astrocyte-neuron communication, lowering neuronal activity in children infected with HIV, which may contribute to the neurodevelopmental delay often observed in this population.

Sphenopalatine ganglion block for the treatment of spontaneous intracranial hypotension without demonstrable cerebrospinal fluid leak: A report of two cases.

Spontaneous intracranial hypotension (SIH) is a condition characterized by orthostatic headache associated with nausea, vomiting, tinnitus, vertigo, hypoacusis, neck pain/stiffness, and photophobia. Usual treatment includes bed rest, hydration, caffeine, analgesics, epidural blood patch, steroids, fibrin glue (N-butyl-cyanoacrylate), and surgical repair. In this series, we report two cases, who presented to us with features of SIH and were managed successfully with sphenopalatine ganglion block. This is a novel modality of management of SIH and has not been reported before.

Blood-CSF barrier integrity in amyotrophic lateral sclerosis.

The integrity of the blood-CSF barrier plays a major role in inflammation, but also in shielding the central nervous system from external and systemic - potentially toxic - factors. Here we report results of measurements of the albumin quotient - which is thought to mirror the integrity of the blood/CSF barrier - in 1059 amyotrophic lateral sclerosis patients. The results were compared with groups of patients suffering from Alzheimer´s disease, facial palsy and tension headache. The albumin quotient, an accepted measure of the blood/CSF barrier integrity, was not significantly different from control populations. In addition, we found that the albumin quotient correlated with survival of the patients; this effect was mainly driven by male patients and influenced by age, BMI and diabetes mellitus. We conclude that the blood/CSF barrier is intact in this large cohort of ALS patients and that the albumin quotient correlates with survival. Whether this is important for the pathogenesis of the disease, requires mechanistic studies.

Comparative analysis of transnasal endoscopic reconstruction techniques for managing cerebrospinal fluid rhinorrhea in skull base defects.

The nasal skull base is located into the deep position of nasal cavity and closely related to important nerves and vessels. The complete removal of tumors in this area poses a complex surgical challenge.In order to investigate the clinical efficacy of utilizing free middle turbinate mucosa (FMT), fascia lata, and pedicled nasal septum flap (known as the Hadad-Bassagasteguy flap, HBF) for the treatment of cerebrospinal fluid (CSF) rhinorrhea, a retrospective analysis was conducted on clinical data from 65 patients who underwent skull base reconstruction following endoscopic resection of nasal-skull base tumors. The selection of the repair material was based on the size and location of the defect. For defects less than 1.5 cm (n = 24), FMT was chosen, while for defects greater than or equal to 1.5 cm (n = 16), HBF was preferred. In cases where HBF was not available or not suitable (specifically, when the defect was located on the posterior wall of the frontal sinus), fascia lata was selected (n = 25). The repair outcomes of all 65 patients were summarized, and subsequently, a comparison was made between the use of fascia lata and HBF. The overall success rate for one-time repairs was 93.8 %. Specifically, the success rates for repairs using FMT, fascia lata, and HBF were 91.7 %, 96.0 %, and 93.8 %, respectively. Throughout the follow-up period, there were 2 cases of postoperative CSF leakage out of 24 patients who underwent FMT reconstruction, 1 case out of 25 patients who underwent fascia lata reconstruction, and 1 case out of 16 patients who underwent HBF reconstruction. The occurrence of postoperative complications, such as intracranial infection, lung infection, and epistaxis, was observed in both the fascia lata group and the HBF group. However, there were no statistically significant differences between the two groups. The transnasal endoscopic reconstruction of skull base defect using HBF, fascia lata, and FMT demonstrated satisfactory repair effects in managing CSF rhinorrhea. Generally, FMT has been found to be a dependable repair material for small defects measuring less than 1.5 cm, while in the case of larger defects equal to or exceeding 1.5 cm, both HBF and fascia lata can be utilized with comparable repair outcomes. The selection of fascia lata becomes a viable option when HBF is unavailable or not suitable.

Unmet needs of biochemical biomarkers for human prion diseases.

Although the development of aggregation assays has noticeably improved the accuracy of the clinical diagnosis of prion diseases, research on biomarkers remains vital. The major challenges to overcome are non-invasive sampling and the exploration of new biomarkers that may predict the onset or reflect disease progression. This will become extremely important in the near future, when new therapeutics are clinically evaluated and eventually become available for treatment. This article aims to provide an overview of the achievements of biomarker research in human prion diseases, addresses unmet needs in the field, and points out future perspectives.

Sterile Cerebrospinal Fluid Ascites With High Serum Ascites Albumin Gradient Treated With Acetazolamide.

Cerebrospinal fluid (CSF) ascites is a rare cause of ascites that presents in patients with ventriculoperitoneal (VP) shunts, treated by conversion to a ventriculoatrial shunt. Our case describes a patient presenting with CSF ascites almost 40 years after VP shunt placement, with fluid analysis showing elevated serum ascites albumin gradient, and response to acetazolamide therapy. As shown in this case, CSF ascites can present with elevated serum ascites albumin gradient and should be kept a differential diagnosis. Acetazolamide can be considered as a potential alternative treatment in patients who are not candidates for a VP to ventriculoatrial shunt conversion.