Viscous CSF may occur with metastatic mucinous adenocarcinoma (e.g., colon), large numbers of cryptococci, severe meningeal infection or, rarely, injury to annulus fibrosus with release of nucleus pulposus fluid.
Turbidity may be due to increased WBC (>200/μL), RBC (>400/μL), presence of bacteria (>105/mL), or of other microorganisms (fungi, amebae), contrast media, epidural fat aspirated during lumbar puncture.
Clots or pellicles indicates protein >150 mg/dL.
Protein >100 mg/dL usually causes CSF to look faintly yellow.
CSF with RBC >6,000/μL appears grossly bloody; with RBC = 500 to 6,000/μL appears cloudy, xanthochromic, or pink tinged (in bright light in clear glass tubes containing >1 mL of CSF). RBC count that decreases between first and last tube indicates traumatic tap (occurs in ≤20% of cases). HSV infection should be considered if CSF RBC >500/μL.
Xanthochromia caused by breakdown of Hb-producing bilirubin, oxyHB, metHb; may be due to:
Bilirubin >6 mg/dL
CSF WBC may be corrected for presence of blood (e.g., traumatic tap, subarachnoid hemorrhage) by subtracting 1 WBC for each 700 RBCs/μL counted in CSF if the CBC is normal.
In normal CSF, ratio of WBC/RBC is <1:500. Minimal blood contamination may cause ≤2 PMN/25 RBCs, or ≤10 PMN/25–100 RBCs.
CSF WBC count (>3,000/μL) with predominantly PMNs strongly suggests bacterial cause and >2,000/μL in 38% of cases. When WBC <1,000/μL in bacterial meningitis, one third of cases have >50% lymphocytes or mononuclear cells. However, WBCs are usually PMNs in early stages of all types of meningitis; mononuclear cells only appear in a second specimen 18 to 24 hours later in nonbacterial cases. Predominantly, lymphocytes occur in ≤10% of ABM cases; may be due to early stages or antibiotic treatment or Listeria meningitis.
May be falsely low due to delay in counting.
Neutrophilic leukocytes are found in:
Bacteria (e.g., Nocardia, Actinomyces, Arachnia, Brucella)
Fungal infections (Blastomyces, Coccidioides, Candida, Aspergillus, Zygomycetes, Cladosporium, Allescheria)
Other conditions (e.g., SLE)
Half-life of neutrophils in CSF is ∼2 hours
Lymphocytic cells are found in:
Bacterial infections (e.g., Treponema pallidum, Leptospira, Actinomyces israelii, Arachnia propionica, 90% of Brucella cases, Borrelia burgdorferi [Lyme disease], M. tuberculosis)
Fungal infections (e.g., Cryptococcus neoformans, Candida species, Coccidioides immitis, Histoplasma capsulatum, Blastomyces dermatitides, S. schenckii, Allescheria boydii, Cladosporium trichoides)
Parasitic diseases (e.g., toxoplasmosis, cysticercosis)
Viral infections (e.g., mumps, lymphocytic choriomeningitis, HTLV-III, echovirus). Atypical lymphocytes may be seen in EBV infection and less often in CMV or HSV infection.
Parameningeal disorders (e.g., brain abscess)
Noninfectious disorders (e.g., neoplasms, sarcoidosis, multiple sclerosis, granulomatous arteritis)
Eosinophils may be found in:
Helminth infection (e.g., angiostrongyliasis, cysticercosis)
Rarely, other infections (e.g., TB, syphilis, Rocky Mountain spotted fever, coccidioidomycosis)
>5% (or >10% neutrophils or significant pleocytosis) may indicate malfunction or infection of a ventriculoperitoneal shunt1
Decreased by utilization by bacteria (pyogens or tubercle bacilli), WBCs, or occasionally cancer cells in CSF
Lags behind blood glucose by about 1 hour
May rapidly become normal after onset of antibiotic therapy
Is decreased in only ∼50% of cases of bacterial meningitis
<45 mg/dL is almost always abnormal; <40 mg/dL is always abnormal
Normally is ∼50% to 65% of blood glucose, which should always be drawn immediately before
Normal CSF:serum ratio of glucose = 0.6. In acute bacterial meningitis (ABM), is usually <0.5; a ratio <0.4 has S/S = 80%/96% for distinguishing ABM from acute viral meningitis (AVM); a ratio <0.25 is found in <1% of AVM cases and 44% of ABM cases, even when CSF glucose is normal. A ratio of <8.0 is significant in infants.
<40 mg/dL in 50% to 60% of ABM cases; <15 mg/dL in 30% of ABM cases
May also be decreased in acute infection due to syphilis, Lyme disease, 10% to 20% of cases of lymphocytic choriomeningitis, and encephalitis due to mumps or herpes simplex but generally rare in viral infections or parameningeal processes. May also be decreased in rheumatoid meningitis, lupus myelopathy, and other causes of chronic meningitis such as bacteria (e.g., Brucella, Mycobacterium tuberculosis), syphilis, fungi (Cryptococcus, Coccidioides), parasites (e.g., cysticercosis), granulomatous meningitis (e.g., sarcoid), chemical meningitis, carcinomatous meningitis, hypoglycemia, and subarachnoid hemorrhage.
CSF protein is least specific parameter
Total protein may be corrected for presence of blood (e.g., due to traumatic tap or intracerebral hemorrhage) by subtracting 1 mg/dL of protein for each 1,000 RBCs/μL if serum protein and CBC are normal and CSF protein and cell count are determined on same tube of CSF. Serum protein levels must be normal in order to interpret any CSF protein values and should therefore always be measured concurrently.
May not be increased in early stages of many types of meningitis
Normal in 10% of patients with ABM (20% of cases of meningococcal meningitis)
Usually >150 mg/dL in ABM; increase occurs especially with S. pneumoniae
<100 mg/dL is usual in nonbacterial meningitis (S/S = 82%/98%)
>172 mg/dL occurs in 1% of AVM and 50% of ABM cases
>500 mg/dL is infrequent and occurs chiefly in bacterial meningitis, bloody CSF, or cord tumor with spinal block and occasionally in polyneuritis and brain tumor
>1,000 mg/dL suggests subarachnoid block; with complete spinal block, the lower the level of the cord tumor, the higher the protein concentration
When antibiotic treatment of bacterial meningitis is started before CSF obtained, protein may be only slightly elevated
May show mild-to-moderate elevation in myxedema (25% of cases), uremia, connective tissue disorders, Cushing syndrome
Decreased CSF protein (3–20 mg/dL) may occur in hyperthyroidism, one third of patients with benign intracranial hypertension, after removal of large volumes of CSF (e.g., during pneumoencephalography, traumatic leaks), in children 6 to 24 months old
Combination of CSF protein, glucose, and WBC levels is more useful than individual parameters.
CSF protein, glucose, and WBC levels may not return to normal in∼50% of patients with clinically cured bacterial meningitis and therefore are not recommended as a test of cure.
CSF lactate has been reported useful to differentiate bacterial from viral meningitis; is independent of serum concentrations. Due to sequelae of increased WBC.
If <3 mmol/L (normal range), viral meningitis is most likely.
If >4.2 mmol/L, bacterial (including TB) or fungal meningitis is most likely.
If 3 to 6 mmol/L with negative Gram stain and prior antibiotic therapy, partially treated bacterial meningitis is most likely. In bacterial meningitis, level is still high after 1 to 2 days of antibiotic therapy.
Mild symptoms with negative Gram stain, few PMNs: CSF lactate may differentiate mild bacterial from very early viral meningitis
May also be increased in non-Hodgkin lymphoma with meningeal involvement, severe cerebral malaria, head injury, and anoxia
CSF and serum ACE are increased in 50% to 70% of cases of neurosarcoidosis; CSF ACE is increased 2×
Reported to be increased in meningitis and Behçet disease and decreased in Alzheimer disease, Parkinson disease, others
CSF chloride reflects only blood chloride level, but in TB meningitis a decrease of 25% may exceed the serum chloride decrease because of dehydration and electrolyte loss. It is not useful in diagnosis of TB meningitis.
CSF glutamine >35 mg/dL is associated with hepatic encephalopathy (due to conversion from ammonia).
CSF IL-6 (marker of inflammation) is increased in bacterial meningitis but not in viral or aseptic meningitis or those without meningitis.
CSF tuberculostearic acid (cell wall component of Mycobacterium tuberculosis) by gas–liquid chromatography has been reported to have good S/S.
Novak R. Cerebrospinal fluid shunts. CAP Today 2004:93.
Increased CSF CEA has been reported helpful in diagnosis of suspected metastatic carcinoma (from breast, lung, bowel) with negative cytology.
Beta-glucuronidase has been reported to be increased in 75% of patients with metastatic leptomeningeal adenocarcinoma and 60% of patients with acute myeloblastic leukemia involving CNS. Normal <49 mU/L, indeterminate = 49 to 70 mU/L, suspicious >70 mU/L.
Lysozyme (muramidase) is increased in various CNS tumors especially myeloid and monocytic leukemias, but is also increased when neutrophils are increased (e.g., ABM).
Minimal residual leukemic disease is detected by flow cytometry since immature leukocytes with these markers (CD10+, TdT+ or CD34+ cells) are not normally present in CSF.
Gamma-aminobutyric acid is decreased in CSF in Huntington disease.
Colloidal gold test is no longer used; replaced by electrophoresis/immunofixation of CSF. IgG in CSF is increased 14% to 35% in two thirds of patients with neurosyphilis. IgG oligoclonal bands may be seen in neurosyphilis and multiple sclerosis.
In eclampsia, CSF shows gross or microscopic blood and increased protein (≤200 mg/dL) in most cases. Glucose is normal. Uric acid is increased (to 3× normal level), in all cases reflecting the marked increase in serum level. In normal pregnancy, CSF values have same reference range as in nonpregnant women.