Cerebrospinal Fluid Glucose and Lactate: Age-Specific Reference Values and Implications for Clinical Practice

Wilhelmina G Leen,Ron A Wevers,Marcel M Verbeek,Michèl A Willemsen,John E Mendelson

doi:10.1371/journal.pone.0042745

Wilhelmina G Leen, Ron A Wevers + Show 3 more

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https://doi.org/10.1371/journal.pone.0042745

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Abstract

Cerebrospinal fluid (CSF) analysis is an important tool in the diagnostic work-up of many neurological disorders, but reference ranges for CSF glucose, CSF/plasma glucose ratio and CSF lactate based on studies with large numbers of CSF samples are not available. Our aim was to define age-specific reference values. In 1993 The Nijmegen Observational CSF Study was started. Results of all CSF samples that were analyzed between 1993 and 2008 at our laboratory were systematically collected and stored in our computerized database. After exclusion of CSF samples with an unknown or elevated erythrocyte count, an elevated leucocyte count, elevated concentrations of bilirubin, free hemoglobin, or total protein 9,036 CSF samples were further studied for CSF glucose (n = 8,871), CSF/plasma glucose ratio (n = 4,516) and CSF lactate values (n = 7,614). CSF glucose, CSF/plasma glucose ratio and CSF lactate were age-, but not sex dependent. Age-specific reference ranges were defined as 5–95th percentile ranges. CSF glucose 5th percentile values ranged from 1.8 to 2.9 mmol/L and 95th percentile values from 3.8 to 5.6 mmol/L. CSF/plasma glucose ratio 5th percentile values ranged from 0.41 to 0.53 and 95th percentile values from 0.82 to 1.19. CSF lactate 5th percentile values ranged from 0.88 to 1.41 mmol/L and 95th percentile values from 2.00 to 2.71 mmol/L. Reference ranges for all three parameters were widest in neonates and narrowest in toddlers, with lower and upper limits increasing with age. These reference values allow a reliable interpretation of CSF results in everyday clinical practice. Furthermore, hypoglycemia was associated with an increased CSF/plasma glucose ratio, whereas hyperglycemia did not affect the CSF/plasma glucose ratio.

Highlights

Cerebrospinal fluid (CSF) analysis is an important tool in the diagnostic work-up of neurological disorders like infection or inflammation of the central nervous system, intracranial hemorrhage and inherited metabolic disorders
To define reference values for glucose and lactate in CSF obtained by lumbar puncture we have excluded (1) all CSF samples from patients from the neurosurgical ward or intensive care units; and CSF samples with (2) an erythrocyte count $200/mL or unknown erythrocyte count; (3) a bilirubin concentration $0.5 mmol/L and/or a free hemoglobin concentration $0.25 mmol/L; (4) an elevated leucocyte count; or (5) an elevated total protein concentration (Fig. 1)
Literature study Reference ranges for CSF glucose, CSF/plasma glucose ratio and CSF lactate based on studies including large numbers of CSF samples were not available

Summary

Introduction

Cerebrospinal fluid (CSF) analysis is an important tool in the diagnostic work-up of neurological disorders like infection or inflammation of the central nervous system, intracranial hemorrhage and inherited metabolic disorders. CSF glucose is decreased in, amongst others, patients with bacterial meningitis and leptomeningeal carcinomatosis, usually in combination with other abnormal CSF parameters, such as an elevated leucocyte count, total protein or lactate concentration [2–4]. Low CSF glucose, often in combination with low CSF lactate, can be found in patients with GLUT1 deficiency syndrome, a treatable genetic metabolic disorder that is caused by impaired glucose transport into brain [5]. CSF lactate can be elevated in several disorders, such as subarachnoidal hemorrhage, bacterial meningitis [3], cerebral hypoxia [6], status epilepticus [7], and inborn errors of metabolism [8]. Age-specific reference values are needed for an accurate interpretation of the results of CSF analysis and differential diagnosis. The main objective of this study was to define age-dependent reference values for CSF glucose, CSF/ plasma glucose ratio and CSF lactate for everyday clinical practice. We aimed to determine the correlations between CSF glucose or CSF/plasma glucose ratio and plasma glucose in order to gain a better understanding of the dynamics of glucose transport of glucose into brain under physiological as well as pathological (i.e. hypo- and hyperglycemic) conditions

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