Conditions associated with an abnormal CSF analysis include (but are not limited to) the following:
Infectious diseases (eg, encephalitis, meningitis) Intracranial/subarachnoid hemorrhage Primary or metastatic central nervous system (CNS) malignanciesUnder normal circumstances, CSF samples are clear and colorless, appearing similar to water.
Xanthochromia is the term used for any kind of discoloration of CSF. Multiple conditions are associated with xanthochromia, including the following [2, 3, 5] :
Traumatic tap Presence of carotene, melanomaincreased bilirubin concentration - Due to liver diseases, hemolytic diseases (also increased free hemoglobin concentration), inborn errors of metabolism (kernicterus), and the significantly delayed bilirubin clearance that can occur in premature babies; the bilirubin concentration will also be elevated in serum, and patients are often jaundiced
Specific CSF discolorations include the following:
Infectious meningitis - Turbid, milky, cloudy CSF samplesHemorrhage (subarachnoid hemorrhage) or traumatic tap - Pink to orange CSF samples, depending on the concentration of free hemoglobin
Kernicterus - Dark yellow or orange CSF samples with increased bilirubin Meningeal melanosarcoma - Dark CSF samples with increased melaninDisorders affecting the blood-brain barrier and demyelinating conditions - Cloudy CSF samples with increased proteins (above 150 mg/dL), such as albumin and immunoglobulin G (IgG)
Increased carotene - Orange discoloration of CSF samplesIf CSF samples are centrifuged immediately, xanthochromia due to traumatic tap should not occur. However, if CSF samples are carefully centrifuged immediately and the supernatant is still xanthochromic, this indicates that bleeding may have occurred 2-4 hours before sample collection. Furthermore, in about 10% of patients with subarachnoid hemorrhage, the CSF samples might be clear if the samples are collected 12 hours after the hemorrhage occurred.
Typically, high levels of oxyhemoglobin occur in CSF fluid obtained through a traumatic lumbar puncture, in which red blood cells (RBCs) enter the subarachnoid space via direct needle puncture. This interferes with the ability to determine whether xanthochromia, and thus subarachnoid hemorrhage, is present. However, a retrospective study by China et al found that when a repeat lumbar puncture was performed on patients after the initial, traumatic one, it was possible to determine that xanthochromia was absent, thereby ruling out the possibility of subarachnoid hemorrhage. According to the study, the timing of the second puncture must be determined on a case-by-case basis, with repeat punctures in the report being performed an average of 2.4 days after the traumatic puncture. The investigators stated that performing the repeat lumbar puncture too soon (eg, less than 12 hours) after the first could still produce equivocal results, while performing the second puncture too long after the initial one could put the patient at greater risk for morbidity and mortality, due to a missed diagnosis. [6]
Bilirubin evaluation in CSF (and serum) is the most effective biomarker to be considered for evaluation of potential subarachnoid hemorrhage. However, a traumatic tap concurrent with subarachnoid hemorrhage can be confusing to interpret.
A traumatic tap introduces red cells into the CSF, but this contamination clears as the collection proceeds from tubes 1 to 4. In a traumatic tap, bilirubin is not produced, given that bilirubin production is an in vivo process. Spectrophotometric evaluation of CSF can provide additional information regarding the presence of oxyhemoglobin due to traumatic tapping (absorbance peak at 415 nm) and the presence of bilirubin due to subarachnoid hemorrhage (absorbance peak at 476 nm). [7] However, large oxyhemoglobin peaks may obscure the region where bilirubin absorbance is normally measured and render interpretation difficult. A series of interpretative comments is suggested in guidelines from the United Kingdom. [8]
Oily CSF samples are associated with the presence of radiographic contrast media.
There are a few common analytes that are routinely evaluated in CSF: glucose, lactate, glutamine, total proteins, albumin, IgG, and bilirubin.
Changes in glucose concentration
Conditions associated with changes in the glucose concentration of CSF include the following:
Bacterial, fungal, and tuberculous meningitis (but not viral) Primary or metastatic meningeal malignancyThe normal concentration of glucose in CSF samples is 45-80 mg/dL or 60-80% of that in the plasma (for glucose plasma concentrations less than 400 mg/dL).
Absolute decreased CSF glucose level and especially decreased CSF glucose level in relation with serum are usually associated with bacterial or fungal meningitis. However, in patient with a normal CSF glucose concentration but with increased number of WBC, viral meningitis should be suspected. For accurate interpretation of CSF glucose concentration, serum glucose should be evaluated in serum samples collected about 2 hours prior to spinal tapping (allow time for equilibrium) and all specimens (CSF and serum) should be tested immediately to avoid glycolysis. [2, 3]
Laboratory testing methods employ hexokinase (reference method) or glucose oxidase. A patient's serum and CSF samples must both be tested using the same method/instrument for accurate interpretation of results. Glucometers and point-of-care testing (POCT) methods/instruments cannot be used for glucose testing in CSF samples.
Elevation of CSF lactate
Conditions associated with elevated CSF lactate include any condition related to decreased blood flow or hypoxia (eg, head trauma), such as the following: