Are cerebrospinal fluid (CSF) lactate and C-reactive protein (CRP) levels always normal in aseptic meningitis?

CSF Lactate and CRP Are NOT Always Normal in Aseptic Meningitis

The statement is incorrect—both CSF lactate and CRP can be elevated in aseptic meningitis, though they are typically lower than in bacterial meningitis and serve primarily to help differentiate between the two conditions rather than being definitively normal in aseptic disease.

CSF Lactate in Aseptic Meningitis

Expected Values and Overlap

• CSF lactate in aseptic meningitis averages 2.06 mmol/L (range 0.76-4.31 mmol/L), which overlaps with the normal range but can be mildly elevated 1
• The UK Joint Specialist Societies guidelines note that CSF lactate has 93% sensitivity and 96% specificity for distinguishing bacterial from viral meningitis when using a cutoff of 35 mg/dL (approximately 3.9 mmol/L), but this indicates overlap exists below this threshold 2
• A meta-analysis confirmed that while CSF lactate is an excellent discriminator (pooled sensitivity 0.93, specificity 0.96), the cutoff of 35 mg/dL means values below this—which can still be elevated above normal—occur in aseptic meningitis 3

Clinical Interpretation

• The Infectious Diseases Society of America guidelines emphasize that CSF lactate >4.2 mmol/L strongly suggests bacterial meningitis (96% sensitivity, 100% specificity), but values between normal and this threshold occur in aseptic meningitis 2
• The high negative predictive value (97%) makes normal CSF lactate useful for ruling out bacterial meningitis, but mildly elevated values (between 2-4 mmol/L) are consistent with aseptic meningitis 2

Important Caveats

• Other factors can elevate CSF lactate independent of infection type, including cerebral hypoxia/ischemia, anaerobic glycolysis, vascular compromise, and metabolism of CSF leukocytes 2
• Prior antibiotic treatment dramatically reduces the sensitivity of CSF lactate to below 50%, making interpretation unreliable in pretreated patients 2, 3

CRP in Aseptic Meningitis

Serum CRP Patterns

• Serum CRP is typically elevated in bacterial meningitis but can also be elevated in aseptic meningitis, just to a lesser degree 2
• The Infectious Diseases Society of America meta-analysis showed serum CRP sensitivity ranging from 69-99% and specificity from 28-99% for bacterial meningitis, with an odds ratio of 150—this wide specificity range indicates substantial CRP elevation occurs in aseptic cases 2
• The clinical utility of serum CRP lies in its high negative predictive value (99%)—a normal CRP helps rule out bacterial meningitis, but elevated CRP does not confirm it 2

CSF CRP Patterns

• CSF CRP levels are significantly higher in bacterial meningitis compared to aseptic meningitis, but aseptic meningitis can still show elevated CSF CRP 4, 5
• A pediatric study found CSF CRP in aseptic meningitis averaged 0.16±0.36 mg/L compared to 0.95±0.68 mg/L in bacterial meningitis, with a cutoff of 0.17 mg/L providing 95% sensitivity and 86% specificity 5
• CSF CRP sensitivity for bacterial meningitis ranges from 18-100% with specificity 75-100% (OR 241), indicating overlap with aseptic cases 2

Practical Application

• Neither serum nor CSF CRP should be used in isolation to determine whether to initiate antimicrobial therapy 2
• The European Society of Clinical Microbiology guidelines note that in children, elevated CRP and procalcitonin are associated with bacterial infections, but the diagnosis cannot be made with these tests alone 2

Algorithmic Approach to Interpretation

When CSF Lactate and CRP Are Most Useful

1. Use CSF lactate <3.0 mmol/L (or <35 mg/dL) to help rule out bacterial meningitis in antibiotic-naive patients 2, 3
2. Use normal serum CRP (with negative CSF Gram stain) to support withholding antibiotics in low-risk presentations 2
3. Interpret mildly elevated values (CSF lactate 2-4 mmol/L, serum CRP <40 mg/L) as consistent with either aseptic meningitis or early/partially treated bacterial meningitis 2, 1

Critical Pitfalls to Avoid

• Never assume normal values definitively exclude bacterial meningitis—10% of bacterial meningitis cases have <100 cells/mm³, and similar exceptions apply to lactate and CRP 2
• Do not rely on these markers after antibiotic pretreatment, as sensitivity drops dramatically 2, 3
• Remember that other bacterial infections (sepsis, pneumonia) elevate CRP and procalcitonin, limiting specificity for meningitis 2
• Always interpret CSF lactate and CRP in the context of CSF cell count, glucose, protein, Gram stain, and clinical presentation—no single parameter is definitive 2