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Updated: Sep 20, 2026

Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid for the Detection of Central Nervous System Pathogens
Published on: April 17, 2026
New and old diagnostic markers of meningitis in cerebrospinal fluid (CSF)
Tilmann O Kleine1, Peter Zwerenz, Peter Zöfel
1Neurochemistry Department, Centre of Nervous Diseases, Clinicum of the University, D-35033 Marburg, Germany.
Abstract:
Five new markers (tumor necrosis factor TNF-alpha, interleukin IL-1 beta, IL-6, IL-8, lipopolysaccharide binding protein (LBP)) and 11 old classical markers were evaluated in 180 cerebrospinal fluid (CSF) and serum pairs to discriminate acute bacterial meningitis (BM) on admission from aseptic (viral) meningitis (AM), bacterial meningitis treated with antibiotics (TM) from AM, and AM from multiple sclerosis (MS). Statistical tests were computed which classified correctly > or =90% of the patients with BM, TM, AM at a sum minimum of false positive plus false negative results, and which reached additionally > or =90% sensitivity and specificity. To discriminate BM from AM, CSF IL-6 test > or =500 ng/l and CSF IL-1 beta test > or =8 ng/l besides CSF lactate test > or =3.5mM/l and CSF granulocyte test > or =150 M/l were revealed. CSF lactate test > or =3.2 mmol/l discriminated TM from AM. CSF leukocyte test > or =35 M/l discriminated AM from MS. Tests with the new markers were more laborious, expensive, and time consuming compared to CSF lactate test. Test candidates, detecting > or =80% of patients with > or =80% sensitivity and specificity, were evaluated with CSF TNF-alpha, IL-8 and LBP, serum IL-6, CSF leukocytes, lymphocytes and monocytes, Qglucose, CSF total protein, albumin, and Qalbumin. All tests should be reviewed in context of clinical findings to diagnose BM reliably.
Insights
Cerebrospinal fluid (CSF) lactate and interleukin-6 tests effectively differentiate bacterial meningitis from viral meningitis and multiple sclerosis. CSF lactate alone can distinguish treated bacterial meningitis from viral meningitis.
Area of Science:
- Clinical Neurology
- Infectious Diseases
- Biomarker Discovery
Background:
- Accurate differentiation of meningitis types is crucial for timely and appropriate treatment.
- Distinguishing bacterial meningitis (BM) from aseptic meningitis (AM) and multiple sclerosis (MS) presents diagnostic challenges.
- Novel biomarkers are needed to improve diagnostic accuracy alongside established markers.
Purpose of the Study:
- To evaluate new and existing cerebrospinal fluid (CSF) and serum markers for discriminating BM from AM.
- To differentiate treated bacterial meningitis (TM) from AM.
- To distinguish AM from MS using biochemical and cellular markers.
Main Methods:
- Analysis of 180 CSF and serum pairs from patients with BM, AM, TM, and MS.
- Evaluation of five new markers (TNF-alpha, IL-1 beta, IL-6, IL-8, LBP) and 11 classical markers.
- Statistical analysis to determine sensitivity, specificity, and correct classification rates for various diagnostic scenarios.
Main Results:
- CSF IL-6 (≥500 ng/l) and IL-1 beta (≥8 ng/l), along with CSF lactate (≥3.5 mmol/l) and granulocytes (≥150 M/l), accurately discriminated BM from AM (>90% accuracy).
- CSF lactate (≥3.2 mmol/l) differentiated TM from AM.
- CSF leukocytes (≥35 M/l) distinguished AM from MS.
Conclusions:
- CSF lactate and specific interleukin levels are valuable biomarkers for differentiating meningitis types and MS.
- While new markers like IL-6 and IL-1 beta show promise, CSF lactate is a more practical and cost-effective option for certain distinctions.
- All diagnostic tests should be interpreted in conjunction with clinical findings for reliable diagnosis of bacterial meningitis.
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