Dataset Information

The Influence of the Ventricular-Lumbar Gradient on Cerebrospinal Fluid Analysis in Serial Samples.

ABSTRACT: Cerebrospinal fluid (CSF) samples from patients with non-inflammatory neurological diseases are used for control groups in biomarker studies. Since large amounts of CSF are withdrawn, patients with idiopathic intracranial hypertension (IIH) or normal pressure hydrocephalus (NPH) are especially suitable. The serially taken CSF portions are usually collected in different tubes. We aimed to investigate whether the later random choice of one of these tubes for CSF investigations might harbor the risk of different CSF protein findings due to the so-called ventriculo-lumbar CSF gradient. Patients with IIH (9) and NPH (7) were included. CSF was serially taken and collected in six tubes of 5 mL each. Concentrations and CSF-serum quotients of immunoglobulins, albumin and the virus-specific antibody index (AI) were determined in the first, fourth and sixth CSF fraction. CSF immunoglobulin and albumin concentrations and CSF-serum protein quotients were significantly lower in the fourth and sixth CSF fraction compared with the first CSF fraction. Virus-specific AI did not significantly differ in the different CSF fractions. CSF protein analytics should be performed in the first CSF fraction in order to avoid different measurement results and achieve comparability within a control group and between different control and patient groups.

SUBMITTER: Konen FF

PROVIDER: S-EPMC8946585 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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The Influence of the Ventricular-Lumbar Gradient on Cerebrospinal Fluid Analysis in Serial Samples.

Konen Franz Felix FF Lange Peter P Wurster Ulrich U Jendretzky Konstantin Fritz KF Gingele Stefan S Möhn Nora N Sühs Kurt-Wolfram KW Stangel Martin M Skripuletz Thomas T Schwenkenbecher Philipp P

Brain sciences 20220320 3

<h4>Background</h4>Cerebrospinal fluid (CSF) samples from patients with non-inflammatory neurological diseases are used for control groups in biomarker studies. Since large amounts of CSF are withdrawn, patients with idiopathic intracranial hypertension (IIH) or normal pressure hydrocephalus (NPH) are especially suitable. The serially taken CSF portions are usually collected in different tubes. We aimed to investigate whether the later random choice of one of these tubes for CSF investigations m ...[more]

PMID: 35326365

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Project description:BackgroundPathological cerebral conditions may manifest in altered composition of the cerebrospinal fluid (CSF). Although diagnostic CSF analysis seeks to establish pathological disturbances in the brain proper, CSF is generally sampled from the lumbar compartment for reasons of technical ease and ethical considerations. We here aimed to compare the molecular composition of CSF obtained from the ventricular versus the lumbar CSF compartments to establish a relevance for employing lumbar CSF as a proxy for the CSF bathing the brain tissue.MethodsCSF was collected from 46 patients with idiopathic normal pressure hydrocephalus (iNPH) patients during their diagnostic workup (lumbar samples) and in connection with their subsequent CSF diversion shunt surgery (ventricular samples). The mass-spectrometry-based proteomic profile was determined in these samples and in addition, selected biomarkers were quantified with ELISA (S100B, neurofilament light (NfL), amyloid-β (Aβ40, Aβ42), and total tau (T-tau) and phosphorylated tau (P-tau) forms). The latter analysis was extended to include paired porcine samples obtained from the lumbar compartment and the cerebromedullary cistern closely related to the ventricles.ResultsIn total 1231 proteins were detected in the human CSF. Of these, 216 distributed equally in the two CSF compartments, whereas 22 were preferentially (or solely) present in the ventricular CSF and four in the lumbar CSF. The selected biomarkers of neurodegeneration and Alzheimer's disease displayed differential distribution, some with higher (S100B, T-tau, and P-tau) and some with lower (NfL, Aβ40, Aβ42) levels in the ventricular compartment. In the porcine samples, all biomarkers were most abundant in the lumbar CSF.ConclusionsThe overall proteomic profile differs between the ventricular and the lumbar CSF compartments, and so does the distribution of clinically employed biomarkers. However, for a range of CSF proteins and biomarkers, one can reliably employ lumbar CSF as a proxy for ventricular CSF if or a lumbar/cranial index for the particular molecule has been established. It is therefore important to verify the compartmental preference of the proteins or biomarkers of interest prior to extrapolating from lumbar CSF to that of the ventricular fluid bordering the brain.

Project description:Lumbar cerebrospinal fluid (CSF) parameters are widely studied and have wide clinical applications, but ventricular CSF has rarely been studied since it is relatively difficult to obtain. To determine whether there are differences between ventricular and lumbar CSF parameters and whether the differences have clinical significance, we retrospectively reviewed 77 patients with Cryptococcal meningitis who received a ventriculoperitoneal shunt. We analyzed the following parameters: white blood cell count, total protein concentration, CSF/blood glucose ratio, chloride ion concentration, and Cryptococcal count. All parameters between lumbar and ventricular CSF were remarkably different (all p < 0.001). White blood cell count, total protein level and Cryptococcal count were lower in ventricular CSF than in lumbar CSF, while CSF/blood glucose ratio and chloride ion concentration were higher. Compared to patients without ventriculomegaly, patients with ventriculomegaly had a significantly higher total protein concentration in ventricular CSF (p = 0.047). Compared to patients without surgical complications, patients with complications had a significantly lower CSF/blood glucose ratio in ventricular CSF (p = 0.032). The lumbar CSF parameters had no significant differences between these groups. The changes in lumbar CSF indices over time after shunt placement were also analyzed. After shunt placement, total protein concentration was transiently increased, white blood cell count, CSF/blood glucose ratio and chloride ion concentration were continued at the preoperative level until two months after shunting surgery. These findings suggest that the composition of ventricular CSF differs from that of lumbar CSF, and different CSF parameters have disparate rostro-caudal gradients in patients with Cryptococcal meningitis. Furthermore, ventricular and lumbar CSF parameters may have different clinical implications. Transient deterioration of lumbar CSF parameters after ventriculoperitoneal shunt placement may not be due to disease progression, but to change in CSF flow rate by CSF shunts.

Project description:The analysis of cerebrospinal fluid (CSF) is used in biomarker discovery studies for various neurodegenerative central nervous system (CNS) disorders. However, little is known about variation of CSF proteins and metabolites between patients without neurological disorders. A baseline for a large number of CSF compounds appears to be lacking. To analyze the variation in CSF protein and metabolite abundances in a number of well-defined individual samples of patients undergoing routine, non-neurological surgical procedures, we determined the variation of various proteins and metabolites by multiple analytical platforms. A total of 126 common proteins were assessed for biological variations between individuals by ESI-Orbitrap. A large spread in inter-individual variation was observed (relative standard deviations [RSDs] ranged from 18 to 148%) for proteins with both high abundance and low abundance. Technical variation was between 15 and 30% for all 126 proteins. Metabolomics analysis was performed by means of GC-MS and nuclear magnetic resonance (NMR) imaging and amino acids were specifically analyzed by LC-MS/MS, resulting in the detection of more than 100 metabolites. The variation in the metabolome appears to be much more limited compared with the proteome: the observed RSDs ranged from 12 to 70%. Technical variation was less than 20% for almost all metabolites. Consequently, an understanding of the biological variation of proteins and metabolites in CSF of neurologically normal individuals appears to be essential for reliable interpretation of biomarker discovery studies for CNS disorders because such results may be influenced by natural inter-individual variations. Therefore, proteins and metabolites with high variation between individuals ought to be assessed with caution as candidate biomarkers because at least part of the difference observed between the diseased individuals and the controls will not be caused by the disease, but rather by the natural biological variation between individuals.

Dataset Information

The Influence of the Ventricular-Lumbar Gradient on Cerebrospinal Fluid Analysis in Serial Samples.

Publications

The Influence of the Ventricular-Lumbar Gradient on Cerebrospinal Fluid Analysis in Serial Samples.

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