scholarly journals Cerebrospinal Fluid Lactate and Pyruvate Concentrations and Their Ratio in Children: Age-related Reference Intervals

2003 ◽  
Vol 49 (3) ◽  
pp. 487-494 ◽  
Author(s):  
Jean-François Benoist ◽  
Corinne Alberti ◽  
Sandrine Leclercq ◽  
Odile Rigal ◽  
Rosalie Jean-Louis ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Diagnostic Value ◽  
Reference Intervals ◽  
Older Children ◽  
Inborn Errors ◽  
Age Related ◽  
Csf Lactate ◽  
The Central Nervous System ◽  
Lactate And Pyruvate ◽  
Best Fit

Abstract Background: Lactate (L) and pyruvate (P) concentrations in cerebrospinal fluid (CSF) and the L/P ratio have diagnostic value in numerous primary and acquired disorders affecting the central nervous system, but age-related reference values are not available for children. Methods: We analyzed CSF and blood lactate and pyruvate concentrations and their ratio in a 4-year retrospective survey of a children’s hospital laboratory database. Reference intervals (10th–90th percentiles) were established from data on 197 hospitalized children. A recent regression modeling method was used to normalize and smooth values against age. The model equation of best fit was calculated for each variable. Results: Slight age-related variations were shown by the model, with an increase in lactate, a decrease in pyruvate, and a resulting increase in the L/P ratio with increasing age. However, the SD did not vary with age. We defined the upper limit of the reference intervals as the 90th percentiles, which from birth to 186 months of age varied continuously from 1.78 to 1.88 mmol/L (6%), 148 to 139 μmol/L (6%), and 16.9 to 19.2 (14%) for lactate, pyruvate, and the L/P ratio, respectively. At a threshold of 2 (in Z-score units), the sensitivity for a subgroup of inborn errors of metabolism (respiratory chain disorders) was 73%, 42%, and 31% for lactate, pyruvate, and the L/P ratio, respectively. Conclusions: In children, CSF lactate and pyruvate concentrations and their ratio appear to vary slightly with age. Average 90th percentile values of 1.8 mmol/L, 147 μmol/L, and 17, respectively, could be used in infants up to 24 months of age. In older children, age-adjusted reference intervals should be used, especially when values are close to the 90th percentile.

scholarly journals Clinical Utility of Monoamine Neurotransmitter Metabolite Analysis in Cerebrospinal Fluid

2008 ◽  
Vol 54 (4) ◽  
pp. 633-641 ◽  
Author(s):  
Keith Hyland
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Regions ◽  
Reference Intervals ◽  
Catecholamine Metabolism ◽  
Monoamine Metabolites ◽  
Monoamine Neurotransmitters ◽  
Age Related ◽  
Sample Stability ◽  
The Central Nervous System ◽  
Monoamine Metabolite

Abstract Background: Measurements of monoamine neurotransmitters and their metabolites in plasma and urine are commonly used to aid in the detection and monitoring of neuroblastoma and pheochromocytoma and the evaluation of hypotension or hypertension. Measurements of these neurotransmitters and metabolites can also be helpful in the investigation of disorders that primarily affect the central nervous system, but only when the measurements are made in cerebrospinal fluid (CSF). Content: I describe CSF profiles of monoamine metabolites in the primary and secondary defects affecting serotonin and catecholamine metabolism. I outline the methods required to analyze these metabolites together with details of specific sample handling requirements, sample stability, and interfering compounds, and I emphasize a need for age-related reference intervals. Summary: Measured values of monoamine metabolites in CSF provide only a single-time snapshot of the overall turnover of the monoamine neurotransmitters within the brain. Because these measurements reflect the average concentrations accumulated from all brain regions plus the regional changes that occur within the spinal cord, they may miss subtle abnormalities in particular brain regions or changes that occur on a minute-to-minute or diurnal basis. Clearly defined diagnosed disorders are currently limited to those affecting synthetic and catabolic pathways. In many cases, abnormal monoamine metabolite concentrations are found in CSF and an underlying etiology cannot be found. Molecular screening of candidate genes related to steps in the neurotransmission process, including storage in presynaptic nerve vesicles, release, interaction with receptors, and reuptake, might be a fruitful endeavor in these cases.

scholarly journals Cerebrospinal Fluid Protein Concentrations in Children: Age-related Values in Patients without Disorders of the Central Nervous System

2000 ◽  
Vol 46 (3) ◽  
pp. 399-403 ◽  
Author(s):  
Daniel Biou ◽  
Jean-François Benoist ◽  
Claire Nguyen-Thi ◽  
Xuan Huong ◽  
Philippe Morel ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Reference Values ◽  
Total Protein ◽  
Age Groups ◽  
Term Neonates ◽  
Age Related ◽  
The Central Nervous System ◽  
Set Up ◽  
Age Range ◽  
Cerebrospinal Fluid Protein

Abstract Background: The published reference values for cerebrospinal fluid (CSF) total protein concentrations in children suffer from two major drawbacks: (a) the age-related range often is too broad when applied to the steeply falling concentrations in early infancy; and (b) no values have been published for widely used dry chemistry methods. Methods: We conducted a 2-year retrospective survey of CSF results obtained in a children’s hospital with a dry chemistry-based method set up on the Vitros 700 analyzer. Results: The data related to ambulatory children up to 16 years of age and term neonates with no clinical or biological signs of brain disease (n = 1074). Seven age groups with significantly different CSF protein values were identified, and their age-related percentiles (5th, 50th, and 95th) were determined. On the basis of the upper 95th percentile, from age 0 to 6 months the CSF protein concentrations fell rapidly from 1.08 to 0.40 g/L. A plateau (0.32 g/L) was reached from age 6 months to 10 years, followed by a slight increase (0.41 g/L) in the 10–16 years age range. Conclusions: These results imply that CSF total protein concentrations in the pediatric setting, particularly in infants, must always be interpreted with regard to narrow age-related reference values to avoid false-positive results.

Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system

Blood ◽  
2011 ◽  
Vol 117 (11) ◽  
pp. 3140-3146 ◽  
Author(s):  
Alexander Baraniskin ◽  
Jan Kuhnhenn ◽  
Uwe Schlegel ◽  
Andrew Chan ◽  
Martina Deckert ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Diagnostic Accuracy ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Diagnostic Value ◽  
Rna Molecules ◽  
Noninvasive Biomarker ◽  
The Central Nervous System

Abstract The diagnosis of primary central nervous system lymphoma (PCNSL) depends on histopathology of brain biopsies, because disease markers in the cerebrospinal fluid (CSF) with sufficient diagnostic accuracy are not available yet. MicroRNAs (miRNAs) are regulatory RNA molecules that are deregulated in many disease types, including cancer. Recently, miRNAs have shown promise as markers for cancer diagnosis. In this study, we demonstrate that miRNAs are present in the CSF of patients with PCNSL. With a candidate approach and miRNA quantification by reverse transcription polymerase chain reaction, miRNAs with significant levels in the CSF of patients with PCNSL were identified. MiR-21, miR-19, and miR-92a levels in CSF collected from patients with PCNSL and from controls with inflammatory CNS disorders and other neurologic disorders indicated a significant diagnostic value of this method. Receiver-operating characteristic analyses showed area under the curves of 0.94, 0.98, and 0.97, respectively, for miR-21, miR-19, and miR-92a CSF levels in discriminating PCNSL from controls. More importantly, combined miRNA analyses resulted in an increased diagnostic accuracy with 95.7% sensitivity and 96.7% specificity. We also demonstrated a remarkable stability of miRNAs in the CSF. In conclusion, CSF miRNAs are potentially useful tools as novel noninvasive biomarker for the diagnosis of PCNSL.

Association of Cerebrospinal Fluid Deficiency of 5-Methyltetrahydrofolate, but Not S-Adenosylmethionine, with Reduced Concentrations of the Acid Metabolites of 5-Hydroxytryptamine and Dopamine

1994 ◽  
Vol 86 (6) ◽  
pp. 697-702 ◽  
Author(s):  
Robert Surtees ◽  
Simon Heales ◽  
ANN Bowron
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Homovanillic Acid ◽  
Dopamine Turnover ◽  
Inborn Errors ◽  
Methyl Transfer ◽  
Hydroxyindoleacetic Acid ◽  
The Central Nervous System ◽  
Acid Metabolites

1. Folate deficiency, or inborn errors of folate metabolism, cause reduced turnover of 5-hydroxytryptamine (serotonin), and perhaps dopamine, in the central nervous system. The mechanism by which this occurs are not known. One possibility is that this is mediated by deficiency of the methyl-donor S-adenosylmethionine. 2. To test this in humans, we have measured cerebrospinal fluid concentrations of 5-hydroxyindoleacetic acid and homovanillic acid, metabolites of 5-hydroxytryptamine and dopamine, respectively, in children with inborn errors of the methyl-transfer pathway. These children are naturally deficient in 5-methyltetrahydrofolate, S-adenosylmethionine or both before treatment, and replete with S-adenosylmethionine, but not necessarily with 5-methyltetrahydrofolate, during treatment. 3. Children with subnormal cerebrospinal fluid concentrations of 5-methyltetrahydrofolate had significantly reduced concentrations of 5-hydroxyindoleacetic acid and homovanillic acid. Children with subnormal cerebrospinal fluid concentrations of S-adenosylmethionine did not have significantly reduced concentrations of these metabolites. 4. We conclude that the mechanism by which deficiency of 5-methyltetrahydrofolate causes reduced 5-hydroxytryptamine and dopamine turnover is unlikely to be mediated by S-adenosylmethionine.

scholarly journals Point-of-care detection of lactate in cerebrospinal fluid

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
C. Stephani ◽  
A. H. K. Choi ◽  
O. Moerer
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Point Of Care ◽  
Blood Gas ◽  
Csf Drainage ◽  
Increased Risk ◽  
Neurosurgical Patients ◽  
Csf Lactate ◽  
The Central Nervous System

Abstract Purpose Measurements of cerebrospinal fluid (CSF) lactate can aid in detecting infections of the central nervous system and surrounding structures. Neurosurgical patients with temporary lumbar or ventricular CSF drainage harbor an increased risk for developing infections of the central nervous system, which require immediate therapeutic responses. Since blood gas analyzers enable rapid blood-lactate measurements, we were interested in finding out if we can reliably measure CSF-lactate by this point-of-care technique. Methods Neurosurgical patients on our intensive care unit (ICU) with either lumbar or external ventricular drainage due to a variety of reasons were included in this prospective observational study. Standard of care included measurements of leucocyte counts, total protein and lactate measurements in CSF by the neurochemical laboratory of our University Medical Center twice a week. With respect to this study, we additionally performed nearly daily measurements of cerebrospinal fluid by blood gas analyzers to determine the reliability of CSF-lactate measured by blood gas analyzers as compared to the standard measurements with a certified device. Results 62 patients were included in this study. We performed 514 CSF-lactate measurements with blood gas analyzers and compared 180 of these to the in-house standard CSF-lactate measurements. Both techniques correlated highly significantly (Pearson correlation index 0.94) even though lacking full concordance in a Bland–Altman plotting. Of particular importance, regular measurements enabled immediate detection of central infection in three patients who had developed meningitis during the course of their treatment. Conclusion Blood gas analyzers measure CSF-lactate with sufficient reliability and can help in the timely detection of a developing meningitis. In addition to and triggering established CSF diagnostics, CSF-lactate measurements by blood gas analyzers may improve surveillance of patients with CSF drainage. This study was retrospectively registered on April 20th 2020 in the German trial register. The trial registration number is DRKS00021466.

scholarly journals Results of Cerebrospinal Fluid Analysis in 108 Patients With Progressive Multifocal Leukoencephalopathy

2020 ◽  
Author(s):  
Nora Möhn ◽  
Luo Yi ◽  
Thomas Skripuletz ◽  
Philipp Schwenkenbecher ◽  
Anne Ladwig ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Cell Count ◽  
Normal Pressure ◽  
Control Group ◽  
Immunoglobulin Synthesis ◽  
Fluid Analysis ◽  
Natalizumab Treatment ◽  
Csf Lactate ◽  
The Central Nervous System

Abstract Background: Progressive multifocal leukoencephalopathy (PML) is caused by an opportunistic infection with JC polyoma virus (JCPyV) and mainly affects immunocompromised patients. It leads to pronounced demyelination of the central nervous system (CNS) resulting in severe disability or even death. Detection of JCPyV DNA in the cerebrospinal fluid (CSF) is usually accepted as proof for the diagnosis of PML. Values from routine CSF parameters, like CSF cell count, protein concentration, Qalbumin levels, or intrathecal immunoglobulin synthesis are mostly considered as normal; however, this has not been investigated systematically. Methods: We therefore analyzed those standard CSF parameters in a cohort of 108 PML patients that were treated at four different neurological centers in Germany. The patients exhibited different underlying conditions with natalizumab treatment in multiple sclerosis (n=54) and human immunodeficiency virus (HIV)-infection (n=25) being the most frequent. The data were collected at the respective centers in accordance with local requirements and then jointly analyzed. The results of the total PML cohort were compared with a control group of patients with normal pressure hydrocephalus (NPH) and idiopathic intracranial hypertension (IIH) or an HIV group without PML, respectively. Results: The PML group showed an elevated cell count (p<0.001) compared to the control group, however, this effect was mainly driven by HIV-PML patients. This subgroup also demonstrated a significantly higher proportion of patients with a disturbed blood-CSF-barrier function. Immune reconstitution syndrome (IRIS) occurred in 41/108 patients and was characterized by a trend for an increase in CSF cell count (p=0.052), CSF lactate (p=0.052), and an augmented intrathecal immunoglobulin synthesis. Conclusions: This comprehensive, retrospective study on diagnostic results in PML patients provides insight into the CSF findings in patients with PML. It demonstrates that CSF changes in PML patients may be specific for the underlying condition that predisposes for the development of PML and thus data have to be interpreted in this context.

scholarly journals Point-of-care Detection of Lactate in Cerebrospinal Fluid

2021 ◽  
Author(s):  
Caspar Stephani ◽  
Alexis H.K. Choi ◽  
Onnen Mörer
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Point Of Care ◽  
Blood Gas ◽  
Csf Drainage ◽  
Increased Risk ◽  
Neurosurgical Patients ◽  
Csf Lactate ◽  
The Central Nervous System

Abstract Purpose: Measurements of cerebrospinal fluid (CSF)-lactate can aid in detecting infections of the central nervous system and surrounding structures. Neurosurgical patients with temporary lumbar or ventricular CSF-drainage harbor an increased risk for developing infections of the central nervous system which require immediate therapeutic responses. Since blood-gas-analyzers enable rapid blood-lactate-measurements we were interested to find out if CSF-lactate may be reliably measured by this point-of-care technique. Methods: Neurosurgical patients on our intensive care unit (ICU) with either lumbar or external ventricular drainage due to a variety of reasons were included in this prospective observational study. Standard of care included measurements of leucocyte counts, total protein and lactate measurements in CSF by the neurochemical laboratory of our University Medical Center twice a week. With respect to this study we additionally performed nearly daily measurements of cerebrospinal-fluid by blood gas analyzers to determine the reliability of CSF-lactate measured by blood-gas-analyzers as compared to the standard measurements with a certified device. Results: 62 patients were included in this study. 514 CSF measurements were performed with blood-gas-analyzers. 180 of these could be compared to the in-house standard CSF-lactate measurements. Both techniques correlated highly significant (Pearson correlation index 0.94) even though lacking full concordance in a Bland-Altman-plotting. Of particular importance, regular measurements enabled immediate detection of central infection in 3 patients who had developed meningitis during the course of their treatment.Conclusion: CSF-lactate was reliably measured by blood-gas-analyzers and detected developing meningitis timely. In addition to and triggering established CSF-diagnostics, CSF-lactate measurements by blood-gas-analyzers may improve surveillance of central nervous infections in patients with CSF-drainage. This study was retrospectively registered on April 20th 2020 in the German trial register. The trial registration number is: DRKS00021466.

Difficulties in establishing reference intervals for special fluids: the example of 5-hydroxyindoleacetic acid and homovanillic acid in cerebrospinal fluids

2004 ◽  
Vol 42 (7) ◽  
Author(s):  
Jean-Louis Dhondt
Keyword(s):  
Cerebrospinal Fluid ◽  
Homovanillic Acid ◽  
Reference Interval ◽  
Reference Intervals ◽  
Control Group ◽  
Age Related ◽  
Wide Range ◽  
Hydroxyindoleacetic Acid ◽  
Biochemical Measurements

AbstractBiochemical measurements in “special fluids” are complicated with the problem of reference intervals. Reference intervals are difficult to establish for these types of samples since they are usually only collected in patients with clinical suspicion of disease. Determination of neurotransmitter metabolites in cerebrospinal fluid illustrates this difficulty. This paper will review the factors and circumstances that have been identified or are suspected to modifythe concentration of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in cerebrospinal fluid. In addition to obvious parameters such as age-related variation that can affect the concentration of 5-HIAA and HVA in cerebrospinal fluid, a varietyof other factors can explain the wide range of “control” group sizes reported in the literature. Reference intervals must take into account the purpose of cerebrospinal fluid examinations, whether they be prospective studies to explore physio-pathologic relationships or for diagnostic purposes. In the latter case, certain neurological disorders cannot be excluded if a single measured value is within the reference interval.

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