Comparison of Ventricular and Lumbar Cerebrospinal Fluid Composition

Podkovik, Stacey; Kashyap, Samir; Wiginton, James; Kang, Christine; Mo, Kevin; Goodrich, Mackenzie; Wolberg, Adam; Wacker, Margaret Rose; Miulli, Dan E

doi:10.7759/cureus.9315

Cited by 12 publications

(12 citation statements)

References 14 publications

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Section: Discussionmentioning

confidence: 98%

“…Previous research and case studies have found cellularity to be increased in lumbar CSF compared to ventricular CSF [33][34][35][36]. Additionally, both Podkovik et al and Gerber et al noted the risk of these findings impacting early infection diagnostics [34,35]. As a sedimentation effect that may impact clinical decision making have been demonstrated for the lumbar versus the ventricular region, it is somewhat surprising that the local sedimentation effect in the ventricles have not been previously studied.…”

Section: Discussionmentioning

confidence: 99%

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Cerebrospinal fluid cell count variability is a major confounding factor in external ventricular drain-associated infection surveillance diagnostics: a prospective observational study

et al. 2021

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Background External ventricular drain (EVD)-related infections (EVDIs) are feared complications that are difficult to rapidly and correctly diagnose, which can lead to unnecessary treatment with broad-spectrum antibiotics. No readily available diagnostic parameters have been identified to reliably predict or identify EVDIs. Moreover, intraventricular hemorrhage is common and affect cerebrospinal fluid (CSF) cellularity. The relationship between leukocytes and erythrocytes is often used to identify suspected infection and triggers the use of antibiotics pending results of cultures, which may take days. Cell count based surveillance diagnostics assumes a homogeneous distribution of cells in the CSF. Given the intraventricular sedimentation of erythrocytes on computed tomography scans this assumption may be erroneous and could affect diagnostics. Aims To evaluate the consistency of cell counts in serially sampled CSF from EVDs, with and without patient repositioning, to assess the effect on infection diagnostics. Methods We performed a prospective single-center study where routine CSF sampling was followed by a second sample after 10 min, allocated around a standard patient repositioning, or not. Changes in absolute and pairwise cell counts and ratios were analyzed, including mixed regression models. Results Data from 51 patients and 162 paired samples were analyzed. We observed substantial changes in CSF cellularity as the result of both resampling and repositioning, with repositioning found to be an independent predictor of bidirectional cellular change. Glucose and lactate levels were affected, however clinically non-significant. No positive CSF cultures were seen during the study. Thirty percent (30%) of patients changed suspected EVDI status, as defined by the cell component of local and national guidelines, when resampling after repositioning. Conclusions CSF cell counts are not consistent and are affected by patient movement suggesting a heterogeneity in the intraventricular space. The relationship between leukocytes and erythrocytes was less affected than absolute changes. Importantly, cell changes are found to increase with increased cellularity, often leading to changes in suspected EVDI status. Faster and more precise diagnostics are needed, and methods such as emerging next generation sequencing techniques my provide tools to more timely and accurately guide antibiotic treatment. Trial Registration NCT04736407, Clinicaltrials.gov, retrospectively registered 2nd February 2021.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid cell count variability is a major confounding factor in external ventricular drain-associated infection surveillance diagnostics: a prospective observational study

et al. 2021

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“…Also, the comparison between TBI and controls could be somewhat biased considering the location of the CSF collection. Whereas the TBI patients had their CSF samples collected from external ventricular drains, controls had a lumbar puncture for CSF collection, which could affect the composition and content of various purines and their metabolites (Brandner et al, 2013; Hegen et al, 2018; Podkovik et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid purinomics as a biomarker approach to predict outcome after severe traumatic brain injury

Strogulski

Stefani

Böhmer

et al. 2022

Journal of Neurochemistry

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Severe traumatic brain injury (TBI) is associated with high rates of mortality and long‐term disability linked to neurochemical abnormalities. Although purine derivatives play important roles in TBI pathogenesis in preclinical models, little is known about potential changes in purine levels and their implications in human TBI. We assessed cerebrospinal fluid (CSF) levels of purines in severe TBI patients as potential biomarkers that predict mortality and long‐term dysfunction. This was a cross‐sectional study performed in 17 severe TBI patients (Glasgow Coma Scale <8) and 51 controls. Two to 4 h after admission to ICU, patients were submitted to ventricular drainage and CSF collection for quantification of adenine and guanine purine derivatives by HPLC. TBI patients’ survival was followed up to 3 days from admission. A neurofunctional assessment was performed through the modified Rankin Scale (mRS) 2 years after ICU admission. Purine levels were compared between control and TBI patients, and between surviving and non‐surviving patients. Relative to controls, TBI patients presented increased CSF levels of GDP, guanosine, adenosine, inosine, hypoxanthine, and xanthine. Further, GTP, GDP, IMP, and xanthine levels were different between surviving and non‐surviving patients. Among the purines, guanosine was associated with improved mRS (p = 0.042; r = −0.506). Remarkably, GTP displayed predictive value (AUC = 0.841, p = 0.024) for discriminating survival versus non‐survival patients up to 3 days from admission. These results support TBI‐specific purine signatures, suggesting GTP as a promising biomarker of mortality and guanosine as an indicator of long‐term functional disability.

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“…Whereas the TBI patients had their CSF samples collected from external ventricular drains, controls had lumbar puncture for CSF collection, which could affect the composition and content of various metabolites though a specific influence on purines is not known yet (Brandner et al, 2013;Hegen et al, 2018;Podkovik et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid purinomics as a biomarker approach to predict outcome after severe traumatic brain injury

Strogulski

Stefani

Böhmer

et al. 2021

Preprint

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Severe traumatic brain injury (TBI) is associated with high rates of mortality and long-term disability linked to neurochemical abnormalities. Although purine-derivatives play important roles in TBI pathogenesis in preclinical models, little is known about potential changes in purine levels and their implications in human TBI. We assessed cerebrospinal fluid (CSF) levels of purines in severe TBI patients as potential biomarkers that predict mortality and long-term dysfunction. This was a cross-sectional study performed in 17 severe TBI patients (Glasgow Coma Scale < 8) and 51 controls. Two to four hours after admission to ICU, patients were submitted to ventricular drainage, and CSF collection for quantification of adenine and guanine purine-derivatives by HPLC. TBI patients survival was followed up to 3 days from admission. A neurofunctional assessment was performed through modified Rankin Scale (mRS) two years after ICU admission. Purine levels were compared between control and TBI patients, and between surviving and non-surviving patients. Relative to controls, TBI patients presented increased CSF levels of GDP, guanosine, adenosine, inosine, hypoxanthine, and xanthine. Further, GTP, GDP, IMP, and xanthine levels were different between surviving and non-surviving patients. Among the purines, guanosine was associated with improved mRS (p=0.042; r= -0.506). Remarkably, GTP displayed predictive value (AUC=0.841, p=0.024) for discriminating survival vs. non-survival patients up to three days from admission. These results support TBI-specific purine signatures, suggesting GTP as a promising biomarker of mortality, and guanosine as an indicator of long-term functional disability.

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Comparison of Ventricular and Lumbar Cerebrospinal Fluid Composition

Cited by 12 publications

References 14 publications

Cerebrospinal fluid cell count variability is a major confounding factor in external ventricular drain-associated infection surveillance diagnostics: a prospective observational study

Cerebrospinal fluid cell count variability is a major confounding factor in external ventricular drain-associated infection surveillance diagnostics: a prospective observational study

Cerebrospinal fluid purinomics as a biomarker approach to predict outcome after severe traumatic brain injury

Cerebrospinal fluid purinomics as a biomarker approach to predict outcome after severe traumatic brain injury

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