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Cerebrospinal fluid protein concentration in pediatric patients: defining clinically relevant reference values
M Wong1, B L Schlaggar, R S Buller
1Department of Neurology, Washington University School of Medicine, St Louis, MO, USA. wong_m@kids.wustl.edu
Insights
Pediatric cerebrospinal fluid (CSF) protein reference values vary significantly by age, with adult norms being inappropriate. Age-specific CSF protein levels are crucial for accurate diagnosis in children, especially when considering enterovirus-polymerase chain reaction (EV-PCR) results.
Area of Science:
- Pediatric Neurology
- Clinical Chemistry
- Infectious Disease Diagnostics
Background:
- Establishing accurate reference ranges for cerebrospinal fluid (CSF) protein is essential for diagnosing pediatric meningitis.
- Traditional diagnostic criteria may not always align with molecular findings like enterovirus-polymerase chain reaction (EV-PCR).
Purpose of the Study:
- To define age-specific, clinically relevant reference values for CSF protein concentrations in pediatric patients.
- To evaluate the impact of enterovirus-polymerase chain reaction (EV-PCR) positivity on CSF protein levels in children.
Main Methods:
- Analysis of CSF protein concentrations in 906 pediatric patients.
- Derivation of age-dependent reference values from a control group of 225 patients without meningitis or neurologic disease.
- Testing of CSF samples for EV-PCR in a subset of the reference group.
Main Results:
- CSF protein concentration is highest and most variable in neonates (approx. 1.0 g/L), decreasing by 6 months and remaining low until adolescence.
- EV-PCR was positive in 11% of the reference group.
- EV-PCR-positive patients aged 4 months to 14 years showed significantly higher CSF protein levels than EV-PCR-negative patients.
Conclusions:
- CSF protein reference values demonstrate significant age-dependent variations in pediatric populations.
- Adult reference values for CSF protein are not appropriate for children.
- The presence of EV-PCR in some patients without meningitis highlights the need for age-and variable-specific reference groups for laboratory values.
Objectives:
To define clinically relevant reference ("normal") values for cerebrospinal fluid (CSF) protein concentrations in pediatric patients who were evaluated for meningitis by traditional criteria and by enterovirus-polymerase chain reaction (EV-PCR).
Design And Patients:
A cohort of 906 consecutive pediatric patients to receive CSF analysis at St Louis Children's Hospital, St Louis, Mo, from June 1, 1998, to December 31,1998, was studied for clinical and laboratory data. Age-dependent CSF protein concentrations were then derived from a reference group of 225 patients in whom meningitis and other neurologic diseases were excluded by traditional clinical or laboratory criteria (excluding EV-PCR). Available CSF samples from 132 patients of the reference group were subsequently tested for EV-PCR.
Results:
In the reference group, the CSF protein concentration was highest and most variable in neonates, with a maximum of approximately 1.0 g/L. Cerebrospinal fluid protein concentration decreased rapidly to a nadir by 6 months and remained low throughout childhood, rarely exceeding 0.3 g/L and, finally, increasing in adolescence toward adult values. Enterovirus- polymerase chain reaction was positive in CSF of 11% of the reference group, with EV-PCR-positive patients having significantly higher CSF protein concentrations than EV-PCR-negative patients aged between 4 months and 14 years.
Conclusions:
Reference values for CSF protein exhibit a characteristic age dependence in pediatric patients. Continued standard use of adult reference values in the pediatric population is inappropriate. The unexpected finding of a positive EV-PCR in patients not diagnosed with meningitis by traditional criteria further emphasizes the importance of selecting the most clinically relevant reference group for age and other variables when defining normal laboratory values. Arch Pediatr Adolesc Med. 2000;154:827-831