Cerebrospinal Fluid Examination

Aka: Cerebrospinal Fluid Examination, CSF Exam, Cerebrospinal Fluid Abnormality, CSF Analysis, CSF Interpretation, CSF Differential Diagnosis, Cerebrospinal Fluid Analysis

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II. Indications

  1. CNS Infection
  2. Thunderclap Headache (evaluation for Subarachnoid Hemorrhage)
  3. Increased Intracranial Pressure (e.g. Pseudotumor Cerebri, Hydrocephalus)
  4. Neurologic Disorders (e.g. Guillain Barre Syndrome, Multiple Sclerosis)

III. Findings: Normal

  1. CSF Color: Clear
  2. CSF Glucose
    1. Children and Adults: 50-80 mg/dl
  3. CSF to Serum Glucose Ratio
    1. Children and Adults: 0.44 to 0.9
    2. Normal newborn: >60% of simultaneous Serum Glucose
      1. Some guidelines define normal range 0.42 to 1.10
    3. Normal infant: >50% of simultaneous Serum Glucose
  4. CSF Protein
    1. Children and Adults: 20-45 mg/dl
      1. Some guidelines use CSF Protein <50 mg/dl
    2. Normal term newborn: <70 mg/dl
      1. Some guidelines use CSF Protein <150 mg/dl
  5. CSF Chloride 116-122
  6. CSF Opening Pressure
    1. Children >8 years old and Adults: 60 to 250 mmH2O (typically <200 mmH2O)
    2. Newborns and Children <8 years old: 10 to 100 mmH2O
  7. CSF Leukocytes
    1. No Neutrophils and under 6 Lymphocytes
    2. Normal term newborn: <10 WBCs/mm3 (<10% Neutrophils)
      1. Some guidelines use <20/mm3
  8. CSF Leukocyte Differential
    1. Lymphocytes 70%
    2. Monocytes 30%
    3. PMNs rare (PMNs may be normal in newborn)
    4. Eosinophils rare
  9. CSF Lactic Acid
    1. Children and Adults: 11.7 to 21.6 mg/dl
    2. Newborns: 8.1 to 22.5 mg/dl
  10. Gram Stain
    1. Negative for organisms

IV. Findings: Bacterial Meningitis

  1. See Bacterial Meningitis
  2. See Nigrovic Clinical Decision Rule
  3. See Meningitest
  4. CSF Color
    1. Cloudy CSF (may also be green or purulent)
  5. CSF Glucose
    1. CSF Glucose <40% of Serum Glucose has Test Sensitivity of 80%, Test Specificity 98%
    2. CSF Glucose <40 mg/dl (but normal in half of Bacterial Meningitis)
    3. CSF Glucose < 34 mg/dl is highly suggestive of Bacterial Meningitis
  6. CSF Protein >100 mg/dl
    1. Elevated in nearly all cases of Bacterial Meningitis
    2. CSF Protein >220 mg/dl is highly suggestive of Bacterial Meningitis
  7. CSF Leukocytes: Markedly increased Neutrophils
    1. WBC >100/mm3 in 99% of cases and >1000/mm3 in most cases
      1. CSF WBCs >2000/mm3 is highly suggestive of Bacterial Meningitis
    2. WBC may be normal despite culture positive Bacterial Meningitis (6% of cases in some series)
  8. CSF Leukocyte Differential
    1. Neutrophils (PMNs) represent 80-90% of Leukocytes in most cases of Bacterial Meningitis
    2. CSF PMNs >1180/mm3 is highly suggestive of Bacterial Meningitis
    3. Lymphocytes may be predominant (>50%) in up to 10% of Bacterial Meningitis cases
  9. CSF Opening Pressure: increased >200 mmH2O
    1. Opening Pressure >300 mmH2O in 39% with Bacterial Meningitis
  10. CSF lactate >35.1 mg/dl
    1. Not in IDSA guidelines as of 2021
    2. May be useful in differentiating from Viral Meningitis (esp. after neurosurgery)
    3. Sakushima (2011) J Infect 62(4): 255-62 +PMID: 21382412 [PubMed]
  11. Gram Stain
    1. Organisms on Gram Stain has a Test Specificity 97% for Bacterial Meningitis
  12. CSF Culture positive in 70% of cases
    1. CSF Culture detection rates decrease 10-20% if obtained after antibiotics are started
  13. Other Tests
    1. CSF PCR
    2. Consider Latex Agglutination (if Gram Stain Negative or cultures followed antibiotics)
      1. Variable efficacy, and may add little value to other testing (e.g. Gram Stain)
  14. References
    1. Bonadio (1992) Pediatr Infect Dis 11(6): 423-31 [PubMed]

V. Findings: Viral Meningitis

  1. CSF Color: Clear to Cloudy Fluid
  2. CSF Glucose: Normal
    1. May be decreased in mumps or HIV Infection
  3. CSF Protein > 45 (typically near normal)
  4. CSF Leukocyte Count
    1. Typically 100 to 1000/mm3 (higher with Enterovirus Meningitis)
  5. CSF Leukocyte Differential
    1. Increased CSF Lymphocytes
    2. PMNs may be increased in early infection
    3. CSF RBCs may be increased in HSV Encephalitis
  6. CSF Opening Pressure: Normal in most cases (may be increased)
  7. Other Tests
    1. CSF Viral PCR (preferred)
    2. CSF or Serum Arbovirus IgM (e.g. West Nile Virus Encephalitis)
    3. MRI Brain (Encephalitis)

VI. Findings: Fungal Meningitis

  1. CSF Color: Clear to Cloudy Fluid
  2. CSF Glucose < 50 mg/dl
  3. CSF Protein > 45 mg/dl (typically 50 to 250 mg/dl)
  4. CSF Leukocytes
    1. Increased (often >100-200/mm3)
  5. CSF Leukocyte Differential
    1. PMNs may be present early, with later Lymphocyte predominance
    2. Monocytes increased
    3. Eosinophils may be present
  6. CSF Opening Pressure: Increased or variable
  7. CSF Gram Stain: Hyphae may be seen
  8. Other tests
    1. CSF Beta-D-Glucan (Test Sensitivity 95-100%, Test Specificity >83%)
    2. CSF Fungal Culture
    3. CSF Fungal PCR has poor Test Sensitivity (<30%)

VII. Findings: Cryptococcal Meningitis

  1. See Cryptococcal Meningitis
  2. CSF Leukocyte Count: Mildly increased (may be normal in HIV)
  3. CSF Leukocyte Differential
    1. Lymphocytes predominant
  4. CSF Glucose >40 mg/dl
  5. CSF Opening Pressure
    1. Opening Pressure >250 mmH2O in severe Cryptococcal Meningitis (requires VP Shunt, or serial LP if persists)
  6. CSF Protein <40 mg/dl
  7. Other tests
    1. CSF Culture
    2. CSF Cryptococcal Antigen
    3. India Ink Capsule Stain
    4. Latex Agglutination, ELISA or lateral flow assay
    5. HIV Test

VIII. Findings: Parasitic Meningitis

  1. CSF Leukocyte Count: 150 to 2000/mm3
  2. CSF Leukocyte Differential
    1. Eosinophils >10%
  3. CSF Glucose: Normal
  4. CSF Opening Pressure: May be increased
  5. CSF Protein: Increased
  6. Other tests
    1. PCR or ELISA tests for specific organisms

IX. Findings: TuberculosisMeningitis

  1. See Tuberculous Meningitis
  2. CSF Color: Cloudy Fluid
  3. CSF Glucose <40-50 mg/dl (decreased with advanced disease)
  4. CSF Protein 100-200 mg/dl
  5. CSF Leukocytes: 5 to 300/mm3 (500 to 1000/mm3 in up to 20% of cases)
  6. CSF Leukocyte Differential
    1. Early: Neutrophils increased
    2. Later: Lymphocytes increased
  7. Other tests
    1. Repeated acid fast stain and cultures
    2. TuberculosisCSF PCR (56% Test Sensitivity, 98% Test Specificity)
    3. CSF Adenosine Deaminase >10 U/L

X. Findings: Subarachnoid Hemorrhage (SAH)

  1. See Subarachnoid Hemorrhage
  2. CSF Color: Bloody CSF with Xanthochromia
    1. Xanthochromia at 6 hours: 20% of Subarachnoid Hemorrhage
    2. Xanthochromia at 12 hours: 90% of Subarachnoid Hemorrhage
    3. Sentinel bleeds in prior 2 weeks in half of SAH patients may also persist as Xanthochromia
  3. CSF Glucose: Normal or decreased
  4. CSF Protein: >45 mg/dl
  5. CSF Red Blood Cells: Increased >2000/mm3
    1. Decreased RBCs in tube 4 compared with tube 1 suggests Traumatic Lumbar Puncture
    2. However, Xanthochromia is not due to Traumatic Lumbar Puncture unless CSF RBCs >100,000/mm3
  6. CSF Opening Pressure: Increased >200 mmH2O
  7. Other tests
    1. CT Head (most accurate in first 6-12 hours)

XI. Findings: Neoplasm (esp. Leptomeningeal Carcinomatosis)

  1. See Intracranial Mass
  2. Metastatic Leptomeningeal Carcinomatosis may cause Meningitis signs (Headache, Nuchal Rigidity, confusion)
  3. CSF Color: Clear or xanthochromic
  4. CSF Glucose: Normal or decreased
  5. CSF Protein: Normal or increased
  6. CSF Leukocytes: Normal or increased Lymphocytes
  7. CSF Opening Pressure: Increased >200 mmH2O
  8. Other tests
    1. Repeated high volume Lumbar Punctures (>10 ml) and analyzed with flow cytometry, biomarkers
    2. Lesions may not be visible on MRI

XII. Findings: Neurosyphilis

  1. See Neurosyphilis
  2. CSF Color: Clear to cloudy fluid
  3. CSF Glucose: Normal
  4. CSF Protein: >45 mg/dl
  5. CSF Leukocytes
    1. Early: 10 to 400/mm3
    2. Later: 5 to 100/mm3 (decreases with chronic disease, decades)
  6. CSF Leukocyte Differential
    1. Monocytes increased
  7. CSF Opening Pressure: Normal or increased
    1. Often normal in Immunocompromised patients
  8. Other Tests
    1. HIV Test
    2. VDRL (Test Sensitivity <75%, Test Specificity 100%)
    3. CSF Fluorescent Treponemal Antibody or FTA (Test Sensitivity 100%, Test Specificity <70%)

XIII. Findings: Demyelinating Disease (Guillain-Barre Syndrome, Multiple Sclerosis)

  1. See Guillain Barre Syndrome
  2. See Multiple Sclerosis
  3. CSF Color: Clear to cloudy fluid
  4. CSF Glucose: Normal
  5. CSF Protein much greater than 45
  6. CSF Leukocytes: Lymphocytes normal or increased
  7. CSF Opening Pressure: Normal
  8. Other tests
    1. CSF Restricted Oligoclonal Bands (Multiple Sclerosis)

XIV. References

  1. Kooiker in Roberts (1998) Procedures in ER, p. 1067-75
  2. Ravel (1995) Lab Medicine, Mosby, p. 294-9
  3. Tunkel in Mandell (2000) Infectious Disease, p. 974-8
  4. Griffith (1994) Neurol Clin 12:541-64 [PubMed]
  5. Mount (2017) Am Fam Physician 96(5): 314-22 [PubMed]
  6. Seehusen (2003) Am Fam Physician 68:1103-8 [PubMed]
  7. Shahan (2021) Am Fam Physician 103(7): 422-8 [PubMed]

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