What is cerebrospinal fluid (CSF) lactate dehydrogenase (LDH) used for in diagnosing central nervous system conditions?

CSF LDH: Clinical Utility in Central Nervous System Diagnostics

CSF lactate dehydrogenase (LDH) is primarily used as a nonspecific biomarker to support the diagnosis of CNS involvement in hematologic malignancies (particularly leukemia and lymphoma) and to help differentiate bacterial from viral meningitis, though it is unreliable as a standalone diagnostic test. 1

Primary Clinical Applications

Hematologic Malignancy CNS Involvement

CSF LDH elevation serves as an adjunctive marker for detecting CNS involvement in patients with leukemia and lymphoma, though it lacks the specificity needed for definitive diagnosis. 1

• Elevated CSF LDH levels have been associated with CNS involvement in diffuse large B-cell lymphoma (DLBCL) and acute lymphoblastic leukemia (ALL), though these parameters are nonspecific and unreliable for routine diagnosis of CNS disease 1
• When combined with CSF cytology, LDH isoenzyme analysis (particularly LDH5 ≥2.8%) can improve diagnostic sensitivity to 93% with a negative predictive value of 98% for CNS involvement in hematologic malignancies 2
• In ALL patients, elevated CSF LDH (particularly when serum LDH >472 U/L) correlates with CNS involvement detected by flow cytometry, with 61% sensitivity and 62.5% specificity 3
• CSF LDH was elevated in 4 of 6 ALL patients with clinical signs of CNS involvement and in 2 of 17 asymptomatic patients, suggesting potential for detecting subclinical disease 4

Meningitis Differentiation

CSF LDH measurement can serve as an adjunctive test to help distinguish bacterial from viral meningitis, with bacterial infections typically causing more pronounced elevations. 5, 6

• CSF lactate <2 mmol/L helps rule out bacterial meningitis 7
• Bacterial meningitis causes significantly higher CSF LD activity compared to viral infections, with isoenzyme patterns reflecting the predominant cell types (granulocytes vs lymphocytes) 6
• The magnitude of LDH elevation correlates with the severity of bacterial infection and inflammatory cell infiltration 6

Diagnostic Limitations and Pitfalls

The Spanish Lymphoma Group (GELTAMO) guidelines explicitly state that CSF LDH and protein increases are nonspecific and unreliable for routine diagnosis of CNS disease, emphasizing that definitive diagnosis requires positive CSF cytology or flow cytometry. 1

• CSF LDH elevation occurs in multiple non-malignant conditions including hydrocephalus, raised intracranial pressure, and epileptic seizures, limiting its specificity 6
• False elevations can occur with hemolyzed specimens, requiring proper specimen collection and handling 8
• CSF LDH should never be used as a standalone diagnostic criterion—it must be interpreted alongside cytology, flow cytometry, imaging, and clinical context 1

Practical Clinical Algorithm

When evaluating CSF LDH results:

1. In suspected hematologic malignancy CNS involvement: Use CSF LDH as a supportive finding only; always obtain CSF cytology and flow cytometry as primary diagnostic modalities 1

2. In suspected meningitis: Combine CSF LDH with cell count, protein, glucose, and microbiological studies; CSF lactate <2 mmol/L effectively rules out bacterial meningitis 7, 5

3. For isolated mild elevation: Consider repeat measurement and evaluate for hemolysis, recent seizures, or other neurological conditions before pursuing extensive workup 6

4. When LDH is elevated with normal cytology: Consider flow cytometry, which detects CNS involvement at double the rate of cytology alone in ALL patients 3