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Adenosine Deaminase (ADA)(CSF)
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No Fasting Required
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Specialized test to assess Tuberculous Meningitis, especially with lymphocytes
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Adenosine Deaminase (ADA) in Cerebrospinal Fluid - Comprehensive Medical Test Guide
- Section 1: Why is it done?
- Test Overview: This test measures adenosine deaminase (ADA) enzyme levels in cerebrospinal fluid (CSF). ADA is an enzyme involved in purine metabolism and immune cell function. Elevated CSF-ADA levels are highly suggestive of tuberculous meningitis (TB meningitis) and other granulomatous CNS infections.
- Primary Indications for Testing: Suspected tuberculous meningitis diagnosis
- Differentiation of TB meningitis from bacterial or viral meningitis
- Investigation of chronic meningitis or aseptic meningitis
- Evaluation of CNS infections in immunocompromised patients
- Suspected fungal or other granulomatous CNS infections
- Typical Timing: Performed when patient presents with symptoms suggestive of meningitis (fever, headache, neck stiffness, altered mental status). Test is done on initial CSF sample obtained via lumbar puncture. Can be repeated if diagnosis remains unclear or clinical status changes.
- Section 2: Normal Range
- Normal Reference Range: 0-4 U/L (Units per Liter) or 0-10 U/L depending on laboratory methodology
- Units of Measurement: U/L (Units per Liter); sometimes reported as IU/mL (International Units per milliliter)
- Interpretation of Results:
- Normal (Negative): ADA ≤4 U/L - Indicates absence of TB meningitis or other granulomatous CNS infection. Low levels suggest viral or non-granulomatous bacterial meningitis.
- Borderline: ADA 4-10 U/L - Intermediate values requiring careful clinical correlation. May warrant repeat testing or additional diagnostic studies. Clinical presentation is crucial for interpretation.
- Elevated (Positive): ADA >10 U/L - Highly suggestive of tuberculous meningitis. Values >15 U/L are considered very significant. May also be seen in fungal meningitis, brucellosis, or other granulomatous infections.
- What Normal vs. Abnormal Means: Normal ADA indicates no active TB or granulomatous infection in the CNS. Abnormal elevated ADA suggests active immune response typical of tuberculosis or other granulomatous disease affecting the meninges.
- Section 3: Interpretation
- Detailed Result Interpretation:
- ADA 0-4 U/L: Normal result. TB meningitis unlikely. Consider viral meningitis, bacterial meningitis, or non-inflammatory conditions.
- ADA 4-10 U/L: Low-positive/borderline. Clinically significant in appropriate clinical context but not diagnostic alone. Requires correlation with CSF parameters, imaging, and clinical presentation.
- ADA 10-15 U/L: Moderately elevated. Strong suspicion for TB meningitis. Should prompt immediate clinical action and consideration of anti-TB therapy.
- ADA >15 U/L: Markedly elevated. Highly diagnostic for TB meningitis. Sensitivity approaches 90-95% in high-prevalence settings.
- Factors Affecting Interpretation:
- Disease Stage: Early TB meningitis may show only borderline elevations; values typically peak by 2-3 weeks
- Immune Status: Severely immunocompromised patients (CD4 <50 cells/μL in HIV) may have lower ADA levels despite active TB
- Co-infections: Fungal or bacterial co-infections may affect interpretation
- Laboratory Method: Different assay techniques may produce slightly different reference ranges
- Other Conditions: Elevated in sarcoidosis, brucellosis, coccidioidomycosis, histoplasmosis, and other granulomatous CNS diseases
- Clinical Significance of Result Patterns:
- High ADA + lymphocytic pleocytosis + low glucose + elevated protein = Classic TB meningitis pattern with high diagnostic confidence
- High ADA + polymorphonuclear predominance = Suggests early TB meningitis before shift to lymphocytes
- Normal/Low ADA + clinical suspicion = Consider alternative diagnoses, repeat LP, or advanced imaging studies
- Section 4: Associated Organs
- Primary Organ Systems Involved:
- Central Nervous System (CNS): Brain and spinal cord meninges - primary site of infection
- Immune System: T lymphocytes, macrophages, and immune-mediated inflammation
- Lymphatic System: Regional lymph node involvement and dissemination
- Conditions Commonly Associated with Abnormal Results:
- Infectious Causes (Primary): Tuberculous meningitis (TB meningitis) - most common
- Fungal meningitis (Cryptococcus, Coccidioides, Histoplasma, Blastomyces)
- Brucellosis meningitis
- Syphilitic meningitis (neurosyphilis)
- Leptospirosis meningitis
- Non-Infectious Granulomatous Causes: Neurosarcoidosis
- Chronic granulomatous disease
- Diseases This Test Helps Diagnose or Monitor:
- Tuberculous meningitis - most important diagnosis
- Monitoring response to anti-TB therapy (ADA levels decline with effective treatment)
- Chronic meningitis of unknown etiology
- Potential Complications or Risks Associated with Abnormal Results:
- Delayed Diagnosis: Borderline ADA values may cause diagnostic delays and increased CNS morbidity
- Neurological Complications: TB meningitis complications include hydrocephalus, vasculitis, spinal cord involvement
- Permanent Sequelae: Hearing loss, visual impairment, cognitive dysfunction from untreated infection
- Immune Reconstitution Inflammatory Syndrome (IRIS): In HIV patients starting antiretroviral therapy
- Mortality Risk: Untreated TB meningitis has high mortality rate (>90%)
- Section 5: Follow-up Tests
- Additional Tests Based on Elevated ADA Results:
- CSF Microbiological Studies: TB culture and sensitivity (gold standard but slow - takes 2-8 weeks)
- GeneXpert MTB/RIF (rapid TB detection and rifampicin resistance - 2 hours)
- Acid-fast bacilli (AFB) smear microscopy
- Fungal culture and sensitivity
- Bacterial culture and gram stain
- Additional CSF Parameters: CSF cell count and differential
- CSF glucose and protein levels
- CSF lactate (elevated in TB meningitis)
- CSF interferon-gamma (IFN-γ) - alternative marker for TB
- CSF lipoarabinomannan (LAM) - additional TB marker
- Neuroimaging Studies: Brain MRI with contrast - shows meningeal enhancement, tuberculomas, hydrocephalus
- Brain CT - shows complications like hydrocephalus or vasculitis changes
- Systemic Investigation: Chest X-ray - look for pulmonary TB
- Serum TB markers (interferon-gamma release assays - IGRA, or tuberculin skin test - TST)
- HIV testing and CD4 count if status unknown
- Complete blood count (CBC) - assess for anemia, leukopenia
- Liver and renal function tests - baseline before anti-TB drugs
- Monitoring Frequency During Therapy: Repeat CSF analysis: Usually at 2 weeks, 4-6 weeks, and 8-10 weeks into treatment to assess response
- Serial ADA measurement: Should show progressive decline with effective anti-TB therapy
- Clinical assessment: Neurological examination at each follow-up
- Repeat neuroimaging: If clinical deterioration or concerning features on initial scan
- Related Tests Providing Complementary Information: CSF chloride level - typically low in TB meningitis
- CSF albumin and immunoglobulin levels
- PCR-based TB detection in CSF - increasingly available
- Section 6: Fasting Required?
- Fasting Required: NO
- Explanation: Fasting is not required for CSF ADA testing. The test is performed on cerebrospinal fluid obtained via lumbar puncture, not blood. Food or fluid intake does not affect CSF composition or ADA measurement.
- Special Instructions and Medications:
- No medication restrictions: Most medications do not interfere with ADA measurement in CSF
- Antibiotic consideration: Patients may already be on empiric antibiotics at time of LP; this does not contraindicate the procedure
- Anticoagulation: May need to be reviewed; warfarin, aspirin typically OK, but discuss direct oral anticoagulants with physician
- Patient Preparation Requirements:
- Informed Consent: Patient must sign consent form explaining risks and benefits of lumbar puncture
- Pre-procedure Assessment: Neurological examination to rule out increased intracranial pressure; CT/MRI imaging if papilledema or focal deficits suspected
- Positioning: Patient typically seated or lying in fetal position during procedure
- Emptying Bladder: Recommended before procedure for comfort
- Removal of Jewelry: Items from lower back area should be removed
- Post-Procedure Care:
- Bed rest for 30 minutes to 2 hours after procedure
- Increased fluid intake - helps prevent post-LP headache
- Pain management: Acetaminophen or NSAIDs for headache if occurs
- Normal activity: Can resume after observation period if no complications
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